2.4.5 What Parts of the Brain are Connected to the Entorhinal Cortex?
In this article, I will be investigating the function of the hippocampus as a whole and by its parts. But let me first talk about why it is important to consider the whole picture through abstractions and also to dig into the details with specifics.
For the sake of understanding something, many people use abstractions or generalizations about things that they know about vaguely. For example, a person may know that a key is required to turn a car on. But the person may not know the exact mechanisms that are in place inside of the car that registers the key shape, the key turn, the electric current produced as a result, making a spark that causes the pistons to fire, etc.
Likewise, scientists make abstractions about the the human body. For example, scientists believe that the brain is the home of the mind, the command center of the body. This generalization glosses over the intricately detailed structures of the brain which each have specific functions for different things.
One such complex structure is the hippocampus, a seahorse shaped part of the brain that is responsible for learning and making new long-term explicit memories. But the hippocampus has further subdivisions that are responsible for different types of learning and memory encoding.
So starting with the generalization and ending with the specifics, I will now investigate in detail the function of the hippocampus by its whole and its parts.
The hippocampus is a part of the limbic system of the brain that is associated with memories, emotions, and motivation. The Limbic system includes (but is not limited to) the hippocampus, cingulate cortex, amygdala, entorhinal cortex, and the olfactory cortex. And the Limbic system is located right above the brain stem and below the cerebral cortex; lining the edge of the cerebral cortex. Of course, the hippocampus of the Limbic system is highly involved with the production of new memories.
A good example that shows the involvement of the hippocampus with our memories concerns the peculiar case of a man named Henry Molaison, also known as patient H.M. Patient H.M. suffered from chronic epilepsy, which is thought to have been caused by a head injury sustained from a bike accident at age 7. During childhood, the person's brain neurons are extremely excitable to aid in rapid learning and brain development. But in exchange, the developing brain is extremely vulnerable to injuries. Such that a brain injury at a young age can result in permanent damage & complications. Like epilepsy.
An old school graduation photo of Patient H.M. before he went under the scalpel to have his brain picked out to cure his epilepsy.
So in order to attempt to cure his epilepsy, doctors chose to have Patient H.M. undergo bilateral medial temporal lobectomy. Which means to cut out the middle part of the temporal lobe from both hemispheres of the brain. Which included cutting out most of Henry Molaison's anterior hippocampi. Note that this procedure resulted in the remaining hippocampal tissue becoming entirely useless and atrophied because the entire entorhinal cortex was destroyed during the operation. The entorhinal cortex is a brain structure that delivers the major amount of sensory input to the hippocampus. And when a part of the brain lacks stimulation, it atrophies.
Stimulation develops the brain. And the opposite is also true.
After the surgery, Henry Molaison developed severe anterograde amnesia. Which means that he could no longer form new explicit memories. Explicit memories include personal experiences and factual information. But he could still learn or get better at certain visual-motor skills like drawing.
And so what does it mean that Patient H.M. couldn't form new memories? Well, essentially Patient H.M. was stuck in the past because he wasn't able to remember information long-term. So that every day that passed him was the same day to him- according to his memory.
To conclude, Patient H.M. has taught us that the hippocampus and other associated structures of the temporal lobe are required for the formation of new long-term explicit memories, including episodic memories of personal experiences, and semantic memories pertaining to factual information & language.
Additionally, you may note that the hippocampus is needed for response inhibition and the formation of spatial memories.
The response inhibition functions of the hippocampus was discovered by scientists who observed animals who suffered damage to the hippocampus became hyperactive. Secondly, animals with hippocampal damage have a hard time learning to inhibit responses previously taught, especially if the response requires remaining quiet.
So generally speaking, the hippocampus is required for the formation of long-term explicit memories. But what exactly does each part of the hippocampus do? To answer this question, we must first identify what parts make up the hippocampus.
Let's start by first making 2 categorizations: the hippocampus and the parahippocampus. The hippocampus may refer to the hippocampus proper, and the dentate gyrus. The hippocampus proper and the dentate gyrus fit together like 2 pieces of a puzzle.
And the parahippocampus may refer to the entorhinal cortex, the subicular cortex, and a few other structures. The parahippocampus formations are next to and kind of surround the normal hippocampus formations. Another definition for parahippocampus is the cortical region of grey matter that surrounds the hippocampus.
Generally speaking, the functions of the hippocampus include memory formation, spatial navigation, and control of attention functions. And the function of the parahippocampus also involves memory encoding and retrieval.
One subregion of the hippocampus is the Dentate Gyrus (DG). The dentate gyrus has functions involving the mnemonic (memory) processing of spatial information, the formation of episodic and spatial memories, and the spontaneous exploration of novel environments. The dentate gyrus may also play a role in depression.
The dentate gyrus is the input region of the hippocampus, and serves as a pre-processing unit. Specifically, information from the entorhinal cortex directly enters the dentate gyrus, is processed by dentate gyrus, and then the processed information is delivered to the CA3 region of the hippocampus proper. The processing the dentate gyrus may perform includes pattern separation, which is separating relatively similar input patterns into distinct/unique output patterns.
Spatial navigation and memory is highly dependent on the dentate gyrus. In an experimental study that destroy the majority of the dentate gyrus in rodents, they showed that the rats experienced extreme difficulty in maneuvering through a maze that they have been through before the dentate gyrus was destroyed. When the rodents without the dentate gyrus were tested a number of times to see if they could learn the maze, the scientists found that the rats treated the maze every time as if they were seeing it for the first time. In other words, the rats without the dentate gyrus could not improve and thereby could not learn the maze, showing a severe impairment to working memory. The rats could not consolidate learned information about a maze through their working memory, and could not remember previous navigation through the same maze. To summarize, the study indicates that the dentate gyrus provides functions such as working memory and memory consolidation for spatial information required for navigation.
The dentate gyrus is one of the regions of the brain that experiences LTP. Generally speaking, Long-Term Potentiation (LTP) occurs in the hippocampus for the formation of new memories. LTP is the long-lasting strengthening of synaptic connections after repeated stimulation. So when a piece of information is repeated again and again, the dentate gyrus preserves that information in the form of strengthening certain synapses (LTP).
The dentate gyrus is also one of the few brain structures that have high rates of neurogenesis in many species of mammals, like rodents and primates. An increase in neurogenesis of the dentate gyrus is associated with improved spatial memory in rodents. Neurogenesis in the dentate gyrus helps with the storage & processing of spatial information.
So how would neurogenesis help with information processing? Well, some scientists hypothesize that newly formed dentate gyrus cells/neurons may be used preferentially to store newly formed memories. And through this mechanism, memories from new dentate gyrus cells can be compared to memories from older dentate gyrus cells, allowing the distinguishment of newer memories from older memories at the same location. Similarly, the dentate gyrus has a pattern separation/completion function that relies on neurogenesis.
Adult-born granule cells (GCs), a minor population of cells in the hippocampal dentate gyrus, are highly active during the first few weeks following functional integration into the neuronal network (young GCs), distinguishing them from less active older adult-born GCs and the major population of dentate GCs generated developmentally (together, old GCs). We created a transgenic mouse in which output of old GCs was specifically inhibited while leaving a substantial portion of young GCs intact. These mice exhibited enhanced or normal pattern separation between similar contexts that was reduced following removal of young GCs by X-ray irradiation. Furthermore, mutant mice exhibited deficits in rapid pattern completion. Therefore, pattern separation of similar contexts requires adult-born young GCs while old GCs are unnecessary, whereas older GCs contribute to the rapid recall by pattern completion. Our data suggest that as adult-born GCs age, their function switches from pattern separation to rapid pattern completion.
So to summarize, the study found that new neurons in the dentate gyrus have the function of pattern separation, whereas the older dentate gyrus neurons have the function of pattern completion. What does this mean exactly? To break it down for you, pattern separation is the ability to distinguish one pattern from another. Whereas pattern completion is the ability to complete or finish a partial pattern.
A linguistic example of completion is "to be or not to _", "look before you _", and "time and tide waits for _". Although you do not have the full pattern, you should be able to tell what comes next because your brain completes the pattern for you. Likewise, the dentate gyrus mediates pattern completion, but particularly for spatial data.
Although the dentate gyrus may be able to deal with different types of information, it mainly deals with spatial information. And if you think about it, spatial information mainly comes from our environment.
An example of pattern separation done by the dentate gyrus is if we revisit a location, we will be able to notice the changes that have occurred from before and now. This is also a way that the dentate gyrus allows us to notice time (because with time, space also changes). To reiterate, if you revisit a location, say the park, 2 times, you will be able to discern the two events from each other through pattern separation.
And an example of pattern completion done by the dentate gyrus is if you only acquire bits and pieces of spatial data from a revisited environment, you will be able to recognize that environment or location from those bits and pieces. For example, if you mostly forgotten the time you spent in the city of New York (or another place), or if the city has mostly changed, you will be able to remember this environment in your previous experience by looking at remaining landmarks and locations that you still remember. That would trigger further memories of what was before, like how certain buildings changed, or empty parking lots that now have skyscrapers, etc.
Together, the pattern completion and separation functions of the dentate gyrus can help a person identify spatial pictures that change with time. In other words, the dentate gyrus may help us notice the passage of time by identifying the changes in an environment. Maybe because adults experience lower levels of neurogenesis in the brain (& dentate gyrus), they perceive time as moving faster than in their childhood.
You may also want to note that the CA3 region of the hippocampus proper also posses pattern separation and pattern completion functions.
The dentate gyrus is also involved in depression and stress.
Specifically, the level of neurogenesis in the dentate gyrus (and perhaps other regions of the hippocampus) affects depression. So controlling the level of neurogenesis in the dentate gyrus may be a way to treat depression. Indeed, chronic antidepressant treatment works specifically by raising the level of neurogenesis in the dentate gyrus and other regions of the hippocampus. Other factors that increase the level of neurogenesis in the dentate gyrus includes aerobic exercise and environmental enrichment or stimulating the brain through learning. So technically, antidepressants, aerobic exercise, and environmental enrichment are all factors that can improve mood and lift depression.
Staring in front of the computer for hours on end can be quite stressful, and chronic stress leads to lower BDNF expression in the brain.
On the other hand, stress can cause depression by lowering neurogenesis in the dentate gyrus and other hippocampal regions. Specifically, stress causes the activation of the sympathetic nervous system, thereby causing the release of glucocorticoids like cortisol. Chronic elevation of stress hormones in the body causes the hippocampus to atrophy or shrink and inhibit neurogenesis in the dentate gyrus. So you should be able to tell that stress can have a very bad effect on the mind and a person's learning ability.
To summarize, depression could be the result of a loss of neurons in the hippocampus caused by chronic stress. Whereas factors that improve neurogenesis may be able to lift depression and improve mood by reversing the loss of neurons in the hippocampus. Note that the process of increasing hippocampal neurogenesis doesn't spontaneously cause neurons to grow, possibly explaining why some antidepressant medications may take some time until it can treat depression.
And given that much of the brain's neurogenesis is limited to the dentate gyrus, one may conclude that the health of the dentate gyrus or its rate of neurogenesis influences a person's mood.
So I previously mentioned that glucocorticoids, a.k.a. stress hormones, can negatively impact the function and health of the hippocampus and the dentate gyrus. But where do stress hormones come from? Well, their production may be stimulated in the body (endogenous), or they can come from outside sources (exogenous).
An example of endogenous glucocorticoid is cortisol and adrenaline released in response to excitement or fear. And an example of exogenous glucocorticoids are those consumed from the meat of sickly caged farmed chicken, because their poor living conditions and diet causes them to experience a high level of stress, which in turn causes their meat to saturate with glucocorticoid stress hormones.
My personal insight that I would like to share is that a person's stress levels can increase quite significantly when their diet is poor. Poor digestion or a poor choice of food influences the type of microbial population that dominates in the gut. For enhanced cognitive function, it is better to consume more vegetables and some fruit, because the fiber they contain acts as a prebiotic- food for growing populations of good microbes, or "probiotics". Whereas too many processed foods influence the populations of microbes that aren't as good for cognitive function. The microbes in your gut are relevant because they are basically pharmaceutical factors that output many different neurotransmitters- in fact, the majority of serotonin in the body is produced in the gut by bacteria.
Glutathione in our body's main antioxidant that protects us from oxidative stress caused by free radicals.
Revisiting the topic of processed foods, they also lack quite a bit of natural antioxidants, which are invaluable for healthy cognitive function. Antioxidants help protect against oxidative stress. So a diet deficient in natural antioxidants results in the brain experiencing increased oxidative stress, which inhibits neurogenesis.
Another topic I'd like to touch is music. Music is quite a double edge sword that I would prefer not to use again. Generally speaking, music raises stress levels for as long as you listen to it. So although you might experience a boost in arousal & focus when listening to music short term, long term constantly listening to music hour after hour everyday harms hippocampal function. I used to listen to music constantly for long periods of time while I worked. As a result, I personally found that my critical thinking, focus, and working memory became impaired. As of 2017 or -18, I find it harder to remember events that occur recently in my life in detail.
But the good news is that after I stopped listening to music constantly, and my overall cognitive memory deficits related to hippocampus and dentate gyrus seems to be slowly getting back to normal.
The functions of the hippocampus proper includes encoding and retrieving spatial memories, episodic memories, autobiographical memories, context-dependent learning, being able to tell how much time has passed from one event to another, and more.
The hippocampus proper is a part of the hippocampus and is composed of 4 sections: CA1, CA2, CA3, and CA4. These 4 sections come together to make kind of a biological circuit composed of neurons (neural circuit) that encodes & processes different types of memories.
CA1 is the first region of the hippocampal neural circuit, which outputs information to the V layer of the entorhinal cortex and to the subiculum.
The CA1 region accepts input from the CA2 region and the CA3 region. The CA2 region sends temporal data, whereas the CA3 region sends spatial data. The CA1 region then combines both the temporal and spatial information into one. So one of the functions of the CA1 region may be to produce combined spatial-temporal code that allows an animal to distinguish the memory of 2 events from each other, even if they occur at the same place but in different times.
Another function of the CA1 region is the retrieval of episodic autobiographical memory.
Specifically, one study examined patients who suffered from a rare acute transient global amnesia. Meaning a full (global) amnesia that does not last (transient). These patients are observed to have lesions that are focused and confined to the CA1 field of the hippocampus.
It was observed from these patients that the CA1 lesions caused a disturbance to autobiographical memory for all time periods, including 30 to 40 years into the past. These results indicate that the function of the CA1 region is in autobiographical memory retrieval that allows a person to re-experience detailed episodic memories about the past.
Another function of the CA1 and CA3 regions involves a type of context-dependent learning. Specifically, the CA1 and CA3 regions contribute to the acquisition of context-dependent extinction, but only area CA1 is required for contextual memory retrieval.
A diagram that shows the anatomy of the CA1, CA2, CA3 regions and the Dentate Gyrus, Entorhinal Cortex, hippocampus, and parahippocampal gyrus. The diagram also shows the neural circuit or flow of information between the CA1, CA2, CA3, and CA4 regions of the hippocampus.
But what does this mean? To understand, first know that scientists may conduct tests based on Pavlovian fear conditioning. For example, in this study the scientists presented to lab rats a conditional stimulus (e.g. auditory sound) simultaneously with a unconditional stimulus (e.g. foot shock). By doing so, the scientists trained the lab rats to associate the auditory sound with the foot shock. So that when the auditory sound is presented, even in the absence of the foot shock, the lab rats freeze-up in anticipation of the foot shock.
Then the conditional stimulus is presented again and again without the unconditional stimulus, causing the rats to learn to no longer associate the auditory sound with the foot shock, so that they eventually stop freezing-up when presented with the conditional stimulus. In other words, the lab rats learn to decrease their fear response, and this is known as fear extinction. Fear extinction is an inhibitory type of learning that allows animals to adapt their behavior to a changing environment. But do note that extinction is not the erasure of the original learning, but rather it involves new learning.
So in the 1st experiment, lesions were made on the CA1 or CA3 regions before fear extinction training. Scientists found that the context-dependence of fear extinction was eliminated. Understand that the word context refers to environment that the rats received conditional stimulus (the auditory sound). So that means scientists found that those lesioned rats had extinguished fear that was no longer dependent on the environment that they received the conditional stimulus. Normal rats would experience a renewal of their extinguished fear if they received the conditional stimulus in a new context (environment). But the CA1 or CA3 lesioned rats did not experience that renewal in fear, showing that both the CA1 region and the CA3 region is involved in the acquisition or encoding of context-dependent fear extinction.
If you ask me, it's like the rats need the CA1 and CA3 regions for a triple association. Meaning that they learn not to fear the auditory sound on the condition that the environment is the same and if there is no foot shock. If the environment changes, then the rats would fear the auditory sound. So the CA1 and CA3 regions cause the rats to be able to make spatial-associations in their learning.
In the 2nd experiment, lesions were made on the CA1 or CA3 region after fear extinction training. Scientists found that only the CA1 lesions impaired the context-dependence of fear extinction. To explain, know that after the rats learned fear extinction, those that got lesions to the CA3 regions could still associate the context with their fear extinction. Meaning that these rats experienced fear renewal when provided with the auditory sound, new environment, and without the foot shock.
But rats that received lesions to their CA1 region after the fear extinction training could no longer associate the context to their fear extinction. So these rats would not experience fear renewal to the auditory sound, even if their environment changed. That means the CA1 region is required for contextual memory retrieval. In other words, the function of the CA1 region is to deliver contextual spatial memory that is associated with fear extinction or a conditional stimulus. Without the CA1 region, an animal wouldn't be able to tell which specific environment it learned not to respond to a conditional stimulus.
The CA2 region is a part of the hippocampus proper, sandwiched in between CA1 and CA3 regions, and the CA2 region receives input from layer 2 of the entorhinal cortex through the perforant pathway. Note that the perforant pathway is a connective route from the entorhinal cortex to all regions of the hippocampus formation, including the dentate gyrus.
The CA2 contains pyramidal cells that are more similar to CA3 than CA1. And the CA2 neurons carry less spatial information than those in the other CA regions. These findings are consistent with the idea that CA2 neurons play some part in spatial processing, although perhaps not to the extent the neighboring CA1 and CA3 regions.
The CA2 area also contains place fields. A place field is a designated place that activates specific place cells in an animal. And a place cell is a type of pyramidal neuron in the hippocampus that activates when the animal enters a specific place in its environment. In other words, an animal can map his physical environment with a neural representation consisting of place cells.
And so a distinguishing feature of the CA2 region is that its place fields "change more in response to the passage of time (hours to days) than in response to alterations in the shape of a context".
So that means the CA2 region encodes time information more strongly than spatial information. In other words, changes in time engage the CA2 region more so than spatial changes (which is like a change in the environment).
Note that the CA2 region sends its temporal information to the CA1 region, and the CA3 region sends its spatial information to the CA1 region. The CA1 region receives inputs from both these regions (as well as others), and combines the two inputs, producing spatial-temporal information or time-dependent information. In other words, the CA1 region produces spatial information that has a time stamp on it.
For example, if a rat visits the same place twice, the spatial information might be same, but the times will be different. So although the CA3 region may register the space as the same for both visits, the CA2 region would register the time of the events as different. And the CA1 region would combine both the space & time information, producing 2 distinct spatial-temporal data sets, registering that 2 distinct events occurred- even if it is in the same place. I believe it is because of the temporal function of the CA2 region and the CA2 region's input to the CA1 region that we can notice and register the passage of time, even in the same environment.
The CA2 region also has a function pertaining to social behavior, evident by the CA2 area containing pyramidal neurons that express high levels of receptors for the 'social' neuropeptides like vasopressin and oxytocin. So the CA2 region may be involved in social memory processing.
When scientists silenced CA2 neurons, it resulted in the impairment of social recognition memory. However, other hippocampus-dependent memory tasks were not harmed, such as novel object recognition and spatial memory. For example, mice with CA2 neuron silencing were unable to differentiate between new and familiar mice, demonstrating that the CA2 region is essential for social memory encoding.
The CA3 subregion receives input from both the mossy fibers of the granule cells in the dentate gyrus, and from cells in the entorhinal cortex through the perforant pathway.
The CA3 region is considered to be the "pacemaker" of the hippocampus, and thereby has a big role in learning. Let me explain below.
When the CA3 region is artificially activated, it mimics the neuronal activity found during a seizure.
From this piece of information alone, you'll be able to get an idea of what the function of the CA3 region may be. To help you understand why seizures are relevant, let me take alcoholics as an example. People who drink alcohol suppress the activity of their Central Nervous Systems (CNS). The result is that Long-Term Potentiation (LTP) of synapses that is required for learning is reduced. And Long-Term Depression (LTD) that is associated with forgetting is increased. Severe alcoholics who suddenly stop drinking alcohol experiences extreme withdrawal symptoms, including seizures.
So what does seizures tell you about the CA3 region of the hippocampus? Well, first know that seizures are caused by the over-activation of neurons, resulting in abnormal electrical activity.
So what does this example tell you about how the CA3 region of the hippocampus works? My conjecture is that depending on the amount of stimulation you receive to the CA3 region, it controls the LTP and LTD of hippocampal synapses for remembering and forgetting. If there is a disturbance in the CA3 region, then hippocampal LTP and LTD will become abnormal. So we may need healthy function of the CA3 region of the hippocampus proper for proper learning. When we learn a piece of information, our brain retains what is most salient (important) and forgets the less relevant details. For this reason, you may want to study in a learning environment with less stimuli or distractions so that the information you are learning becomes more "salient" to your brain. I personally have found that working in a noisy environment, such as with music, decreases the amount of information you encode and retain from a study session. Noisy environments not only increases cortisol, which can cause atrophy of the hippocampus if exposed long-term, but also disrupts the electrical wave rhythm set by the CA3 region.
CA3 functions as a pacemaker, my conjecture is that it controls how sensitive the hippocampus is to LTP and LTD.
Another consideration, albeit a bit off topic, is that the hippocampus is one of the primary regions of the brain that can cause epilepsy through abnormal function. That means if a person's hippocampus is damaged, say by falling on one's head, then his chance for acquiring epilepsy is increased. Due to this association, many seizure patients used to end up having their hippocampus & related brain regions surgically removed as an attempt to cure their epilepsy. A prime example is patient H.M.
dentate granule cells operated as a preprocessing stage for the CA3 region by performing pattern separation so that the mossy fibers could act to set up different representations for each memory to be stored in the CA3 cells.
It will be suggested below that an autoassociation memory implemented by the CA3 neurons enables event or episodic memories to be formed by enabling associations to be formed between spatial and other including object representations.
The concept that the CA1 recodes information from CA3 and sets up associatively learned backprojections to neocortex to allow subsequent retrieval of information to neocortex is consistent with findings on consolidation.
The CA3 region is also involved in the acquisition of context-dependent fear extinction- you can read more about it above in the CA1 section of this article.
The functions of the subiculum deals with the fact that it is the main information output target of the hippocampus. Specifically, the subiculum has functions pertaining to memory, spatial navigation, mnemonic or symbol processing, and regulating the body's response to stress through the inhibition of the HPA axis.
Before I go into more detail about the functions of the subiculum, let me first talk a bit about the location & structure of the subiculum. Because in order to understand the functions of the subiculum, it helps to understands the location and structure that the functions are based off of first.
The subiculum is an important part of the hippocampal circuit. So structurally, the subiculum is a subdivision of the hippocampal formation that is located in the mesial temporal lobe. Furthermore, the subiculum occupies a portion of the parahippocampus gyrus inside of the mesial temporal lobe.
The subiculum is the lowest part of the hippocampal formation. The subiculum is located in between the front of the entorhinal cortex and CA1 subfield of the hippocampus proper. Dorsally or towards the top, the subiculum is bordered by the retrosplenial cortex.
As a structure of the brain, the subiculum is broken down into different regions according to different cytoarchitectures or cell architectures. Note that the subiculum or subicular complex has slight variations between humans, monkeys, and rodents. And in general, the architecture of the brain differs between species.
The subiculum is composed of 3 layers: a molecular layer, an enlarged pyramidal cell layer, and a polymorphic layer.
The molecular layer is continuous with strata lacunosum-moleculare and radiatum of the adjacent hippocampal area CA1 field.
The enlarged pyramidal cell layer contains the soma of principal neurons. And the cell packing in the pyramidal layer of the subiculum is looser than in the CA1 hippocampal area.
The subiculum can be divided into 5 subregions: the prosubiculum, presubiculum, postsubiculum, parasubiculum, and subiculum proper. All together these subregions are known as the subicular complex.
Note that the prosubiculum and postsubiculum may or not exist in rats- there is no consensus on this in the scientific community.
I also have noticed that much like the entorhinal cortex, the subiculum constantly responds to an influx of information. For example, some hippocampal neurons may selectively respond to only familiar objects or a landmarks. But like the entorhinal cortex, the subiculum constantly responds to concurrent location and speed. Thereby providing other brain regions with this constantly updated information. I suspect the parasubiculum and the postsubiculum are responsible for generating this information, and other parts like the presubiculum to deliver this information. But remember, this is just my conjecture.
The parasubiculum has grid cells- a type of neuron that responds to movements in a particular direction over a certain amount of distance.
So you can assume the parasubiculum monitors and remembers directional movement over distance.
The presubiculum is a part of the posterior cortex that also coincides in the brodmann's area 27. The presubiculum delivers information to the entorhinal-hippocampal spatial-memory system.
The dorsal or top-part of the presubiculum is known as postsubiculum. The postsubiculum contains head direction cells that responds to the direction the head faces to. You can assume that the postsubiculum monitors and keeps in memory the direction a person's own head faces and relays that information to other brain regions.
The prosubiculum is the region between the CA1 region and the subiculum. This area has high cell density that is smaller in size compared to other regions.
The ventral subiculum projection system projects to a distributed forebrain limbic system associated with inhibitory input to the hypothalamic–pituitary–adrenal (HPA) axis and the hypothalamic–spinal–adrenal (HSA). Inhibition of the HPA axis is thought to be mediated transynaptically via GABAergic neurones that project directly to the paraventricular nucleus or hypothalamic autonomic control systems. Neurons within the median raphe nucleus project extensively and selectively to the ventral subiculum projection system, including the medial hypothalamic defensive system associated with active emotional coping responses.' Thus, the role of the subiculum is to act principally to inhibit the HPA axis, and thus it plays a key role in terminating or limiting the response of the HPA axis to stress.
So you can imagine that the subiculum sends neuronal connections to the hypothalamus, which is right underneath the thalamus. The hypothalamus communicates with the autonomic nervous system. And to raise a stress response, the hippocampus sends a signal to the sympathetic nervous system, telling it to activate. The sympathetic nervous system then triggers the body's fight-or-flight stress response.
So if the Sympathetic Nervous System (SNS) becomes activated, then the SNS sends a signal to the adrenals. The adrenals in turn respond by releasing epinephrine, a.k.a. adrenaline.
And that's why when we talk about the subiculum lowering the stress response, we say it does this through the Hypothalamic-Pituitary-Adrenal axis, or HPA axis for short. And not just mention the hypothalamus all by itself.
One function of the subiculum is that it acts as a relay station, or distribution center of information from the hippocampus. Which makes sense, given that the subiculum is also the main information output target of the hippocampus and is located as such.
When the subiculum receives information from the hippocampus, the subiculum may then send that information to different regions (cortical or subcortical) of the brain. Like the prefrontal cortex and the entorhinal cortex, for example.
Specifically, the subiculum receives information input from the pyramidal neuron projections of the CA1 subfield (a part of the hippocampus proper) and the entorhinal cortical layer III. Note that proximal CA1 neurons project to the distal subiculum, mid-CA1 neurons project to the mid-subiculum, and distal CA1 neurons project to the proximal subiculum; all of these projections cross the CA1-subiculum border.
Likewise, the subiculum sends output information through having pyramidal neurons with projections extending to the nucleus accumbens, septal nuclei, prefrontal cortex, lateral hypothalamus, nucleus reuniens, mammillary nuclei, entorhinal cortex, and amygdala. That means that the subiculum has communications lines sending hippocampal information to these brain regions. Because we know that the information comes from the hippocampus, we can assume that this information may be pertaining to newly formed explicit memories and spatial memories.
Transitions between different behavioral states, such as sleep or wakefulness, quiescence or attentiveness, occur in part through transitions from action potential bursting to single spiking. Cortical activity, for example, is determined in large part by the spike output mode from the thalamus, which is controlled by the gating of low-voltage–activated calcium channels. In the subiculum—the major output of the hippocampus—transitions occur from bursting in the delta-frequency band to single spiking in the theta-frequency band. We show here that these transitions are influenced strongly by the inactivation kinetics of voltage-gated sodium channels. Prolonged inactivation of sodium channels is responsible for an activity-dependent switch from bursting to single spiking, constituting a novel mechanism through which network dynamics are controlled by ion channel gating.
The entorhinal cortex is a brain structure located in the medial temporal lobe and is next to the hippocampus. The entorhinal cortex functions as a type of hub for routing information related to spatial and non-spatial memories. The Entorhinal Cortex (EC) is both the major input and the major output hub of information to and from the hippocampus. And EC also functions as an in between or interface between the neocortex and the hippocampus.
The Entorhinal Cortex (EC) works with the hippocampus formation on declarative/explicit (autobiographical, episodic, semantic) memory storage, and spatial memories in particular. The EC-hippocampus system also collaborates on memory formation, memory consolidation, and memory optimization in sleep.
Note that memories are formed by physical neural changes (memory traces) in response to stimuli. And memory consolidation is the process(es) by which a memory trace is stabilized (synaptic consolidation, LTP) after being acquired, eventually transferring to other brain regions like the neocortex to become permanent/long-term memories. And during sleep, especially slow wave sleep, memories of the previous day are reactivated to be strengthened/consolidated. Which is why sleep is invaluable for learning.
Additionally, the hippocampus and the Entorhinal Cortex (EC) are the key neural structures responsible for our sense of direction and spatial navigation ability. Specifically, the EC includes functions useful for navigation including spatial mapping, speed sensing, and direction sensing.
The ability to find one's way depends on neural algorithms that integrate information about place, distance and direction… the dorsocaudal medial entorhinal cortex (dMEC) contains a directionally oriented, topographically organized neural map of the spatial environment. Its key unit is the 'grid cell', which is activated whenever the animal's position coincides with any vertex of a regular grid of equilateral triangles spanning the surface of the environment. Grids of neighbouring cells share a common orientation and spacing, but their vertex locations (their phases) differ. The spacing and size of individual fields increase from dorsal to ventral dMEC. The map is anchored to external landmarks, but persists in their absence, suggesting that grid cells may be part of a generalized, path-integration-based map of the spatial environment.
The neural map representation of an animal's spatial environment has a specific location within the Entorhinal Cortex (EC). The lateral or "sides" of the EC do not show the existence of a neural map. But the medial or "middle" of the EC shows the presence of place fields arranged in a hexagonal pattern. Remember that a place field a physical space in an animal's environment that is marked or represented by place cells in the hippocampus. Place cells are pyramidal neurons that work together to make a map representation of the animal's environment. When animals enter a place field, the corresponding place cell in the brain may activate in response- almost acting like a neural GPS that helps the animal know where it is in its environment.
The existence of place cells in the medial EC tells us that it mainly represents spatial information, whereas and non-spatial information is mainly represented in the lateral EC given its absence of place cells.
So the medial EC contains place fields arranged in a hexagonal pattern. Because of this pattern, these place fields are also known as "grid cells".
Reiteratively, a grid cell is a type of neuron that allows an organism to understand their position in space. So EC "grid cells" indicates the position of the organism in one of various equally spaced locations in a neural map. Grid cells fire action potentials when the animal passes through a specific small region of space. This is called the "place field" of the cell.
FYI, there are other types of EC cells that have unique navigational functions. For example, EC "border cells" indicates the orientation and distance to the environment's walls. And EC "path equivalent cells" indicates a location's relative position along a common type of route.
The medial entorhinal cortex also contains "speed cells" that has the function of measuring movement speed. These speed cells derive the speed information of the mammal or organism from proprioceptive information.
Note that proprioception refers to the internal stimuli that allows the organism to perceived the position & movement of the body- like the feeling of where your arms are.
Additionally, the movement speed is represented as the signal firing rate of the speed cells. These speed cells fire according to the perceived future speed of the organism.
The Entrohinal Cortex also contains "path cells" that senses changes in direction.
In one study, scientists had test subjects playing a video game, where the person was either taking a clockwise path or an anti-clockwise path. While the tests subjects were doing this, scientists observed the activity of the entorhinal cortex using the single-unit recordings of microelectrodes implanted in or close to the brain. What the scientists observed is that the path cells in the EC activates constantly in response to directional stimuli from the video game being played, irrespective of the location that the person physically experiences in reality. Compare this to the "place cells" in the hippocampus, which activates only in response to specific locations.
Note that place cells in the hippocampus encodes (forms) memories of the current virtual location of the person. And the direction cells in the entorhinal cortex encodes memories of the current direction.
What Parts of the Brain are Connected to the Entorhinal Cortex?
After understanding the major functions of the entorhinal cortex, it may be useful to know the parts of the brain are connected to the entorhinal cortex. Because then you can tell which brain regions take and use information delivered from the entorhinal cortex. And that these brain regions use entorhinal-specific information.
The entorhinal cortex mostly deals with spatial memories and non-spatial explicit memories. So you can tell that brain regions connected to the entorhinal cortex may receive spatial memories, non-spatial memories, and processed spatial information that I mentioned above.
Specifically, the entorhinal cortex has neuronal projections sent to the dentate gyrus, the hippocampus, and the subicular complex.
Our discovery of EC path cells provides a striking demonstration of the broad range of information that may be encoded in EC. In addition to directional information encoded by path cells during navigation, recent studies showed that EC contains neurons encoding a broad range of cognitive information in both spatial and nonspatial tasks, including characteristics of the current behavioral task, future or past movements, the contents of working memory, the objects currently being viewed, the distance to nearby walls, and the current spatial location. Most of these studies analyzed recordings from rodents, and thus it is possible that similar patterns do not exist in humans. Nonetheless, taken together, these findings support the view that the EC plays a pivotal role in memory formation because EC neurons encode attributes of the current context that are subsequently stored by the hippocampus as memories.
The dentate gyrus is involved in the processing of spatial information, the formation of episodic and spatial memories, mood and depression. The CA1 region combines spatial information with temporal information for event discernment, retrieves autobiographical memories, and is need for context-dependent learning and contextual memory retrieval. The CA2 region also deals with some spatial and social memory processing, but moreso encoding temporal information that is sent to the CA1 region for time-stamping spatial information. I believe this is how we are able to have episodic memories, being able to tell when an event happened in respect to others. The CA3 region mainly deals with spatial information. The subiculum acts as a relay station, taking information from the hippocampus and delivering it to other parts of the brain. The subiculum is also involved in memories, navigation, and the body's stress response. Similarly, the entorhinal cortex also functions as a type relay station being the major input and output of information from the hippocampus, and being involved in memory formation, memory consolidation, and processing spatial information.
Overall, the hippocampus is an invaluable part of our brain that allows us to learn new things.


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Q: Using SQL Server specific code in Access linked to SQL Server database I have an access file that is linked (through an ODBC connection) to a SQL Server 2008 database. I am trying to write some reports against this database. However, Access chokes when I write the select query of the report with SQL syntax specific to SQL Server that doesn't exist in access. Shouldn't this work, since it's the SQL Server engine running the queries and just sending the data back to Access to display? Is there any way to get this to work?
Need this to work on any combination of Access 2007 and 2010, and SQL Server 2005 and 2008.
Edit
Note: I cannot create a SQL Server stored procedure or function, or otherwise modify the original (SQL Server) schema in any way.

A: Found the answer: I need to use a "pass-through query".

redpajama_set_name: RedPajamaStackExchange


Seattle and the entire Puget Sound region are among the most pet-friendly areas in the U.S., and we take our commitment to guardianship seriously. We cherish our pets, consider them family. We worry about whether our pets are getting the right foods, the safest toys, the best training and exercise, about whether they are properly socialized, going to the best veterinarians, etc.
If you've ever loved, or are currently in love with a pet, you know the joy of sharing your life with an animal far outweighs the eventual heartache most of us bear when they leave us. It's never easy, but we expect to outlive our pets.
But what happens when they outlive us? Would your pets thrive in your absence?
In Washington State, pets essentially have the same legal status at your death as your sofa – they are personal property. In the absence of another direction in an estate plan, a pet passes to whoever would inherit your other personal property. This can be problematic — while you might want your father or your brother or your daughter to inherit your car or jewelry or sofa, he or she might not be the best person to love and care for your pet.
Sheila is a 26-year-old single woman with two dogs, a lab mix, Baxter, and a golden retriever, Teddy. She hopes to have children one day, but right now her dogs are her "babies." She works hard to satisfy their needs for good nutrition, exercise, medical care, training, and overall well-being. Sheila has a large social network of dog-loving friends.
When Sheila thinks of estate planning – which admittedly, she doesn't often – she thinks it is for someone older, more mature, more settled than she is. But after hearing about Leona Helmsley and her extravagant pet trust, Sheila got to thinking about what would happen to Baxter and Teddy if she were to die unexpectedly.
As much as she loves her parents, Sheila knows Baxter and Teddy would be better off living with Emily, one of her dog-savvy and dog-loving friends.
Although Sheila would like to have Emily care for her pets in the event of tragedy, she isn't sure how that would work – or whether Emily could afford to care for the dogs for their lifetimes.
Sheila and Emily have promised each other that they will care for the other's pets, but this plan is inadequate. Their informal arrangement presents numerous problems.
If Sheila were to pass away without a will, her wishes regarding Baxter and Teddy would not be recorded. There would be competing interests – Sheila's parents, who would inherit the dogs under Washington law, may want to keep the dogs out of a perceived sense of loyalty to Sheila, even though they aren't the best caretakers. And Emily would have no way to enforce Sheila's wishes.
Can Sheila make this work? Yes, instead of making insecure plans with well-meaning friends, Sheila should work with an estate planning attorney to create an estate plan to formalize her goals for her pets.
The issues facing Sheila are similar to the decisions a parent makes with regard to a guardian for a minor child. I encourage pet owners to think about who should care for their pets just as I encourage parents to think carefully about any guardian they name in their wills. A will gives you the power to legally choose who will care for your pet. Your wishes will be clear and enforceable. Having a formal plan also frees family members from the burden of having to make this decision for you when they're already suffering emotional distress.
Once you've taken care of the "who," the next step is making sure the "how" is taken care of, meaning the financial piece of pet guardianship. Caring for pets can be expensive. I encourage my clients to think about how their pet's caretakers will pay for their new family members' care.
Providing financial protection ensures the new guardians will be able to afford the costs of caring for your pet in the manner you designate, including veterinary visits, food, pet sitting, grooming, exercising and more, without bearing the financial burden themselves.
In our own wills, my wife and I have designated portions of our life insurance to cover our dog's expenses for her lifetime. This ensures she will be cared for, without putting a financial burden on her new guardians.
An estate-planning attorney can help you choose the best financial tool for covering the costs of caring for your pet. In many cases, clients can make a simple cash bequest to the new caretakers. Many of my clients, for instance, expect that one of their children will care for their pets when they are gone. I discuss with these clients whether it makes sense to provide an extra bequest to the designated caretaker to cover pet care costs.
Other clients may need to establish more complex structures, which may include a "pet trust" or other financial tool. An estate-planning attorney will help you decide what works best for your situation.
Part 3: Who can best care for my pet?
Recall that in Part 1 of this article Sheila had a good choice to care for her pets in the event of tragedy. Not everyone has that option. What if you don't have someone like that in your life?
Mary is a 76-year-old retired nurse living in Bothell. She has two four-year-old cats, George and Abby. Mary is single, with no children. Although Mary has a rich social life, she does not know anyone who would be a good choice to care for her beloved pets if she were to pass away during their lifetimes.
A pet-savvy estate planning attorney could help Mary find and research other options. For example, some local animal welfare organizations will foster or re-home pets in exchange for a portion of your estate. Or perhaps Mary could appoint an individual or panel to take responsibility for finding the best possible home and guardian for her pet. Regardless of the plan, an estate-planning attorney should be involved to ensure that her wishes are clearly spelled out and legally binding.
Without a designated caretaker, or a plan for finding one, Mary's cats could eventually end up in a shelter. While we are fortunate to have many wonderful rescue organizations in our area, it's important to consider the stress and uncertain future your pet could face with this option. Don't get me wrong, my wife and I are forever grateful to shelters for doing such wonderful work rescuing animals – our own dog's life was saved by two different shelters, and we both continue to support animal welfare organizations –but by making a plan for your pet, not only will you have peace of mind that your pet will be cared for, you'll also avoid burdening the shelter system.
It's more than just setting aside money.
No one knows your pet as well as you do. Documenting what you know will help your pet and a new guardian adapt more quickly to their new lives together. Sharing the basics, such as diet, exercise and medical information is important, but so is describing your pet's personality, including all the quirks that make him or her unique. Listing favorite toys, how s/he likes to be petted (if at all), social skills with other people and animals, and other information will all help everyone bond more quickly.
Our complimentary Pet Profile form can help you pass your knowledge of your pet on to potential caregivers. Simply e-mail us your full name to receive a link to the form.
Identify one or more caretakers for your pets.
Contact an estate planning attorney that shares your concern for your pet's welfare.
Execute a will that includes both a guardian and financial support for your pets.
Email me for a Pet Profile form and share it with family members, identified caretakers, and veterinarians, and keep a copy with your will.
Enjoy peace of mind that your commitment to your pets will last for their lifetimes.
Most everyone knows they should have an estate plan. The reality is that many people don't bother to make one until they're touched by a life event that highlights the perils of not having a plan.
Talk with an estate planning attorney that understands the issues surrounding pets in estate plans, one that shares your concerns about pet welfare. Including your pet in a will is the best way to truly make a lifetime commitment for your pet.


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In partnership with The Water Council, Neroli and Aveda Institutes announce Future Water Leaders Fund winners
The selected winners will be awarded funds at an upcoming Water Council Membership Meeting.
By The Water Council	- Nov 5th, 2019 06:59 am
MILWAUKEE (Nov. 5, 2019) – The Water Council, along with Neroli Salon & Spa, The Institute of Beauty and Wellness and Aveda Institute Madison have selected two projects to receive funding through the second annual Future Water Leaders Fund that will support student-led water-related projects or research efforts in Wisconsin.
Aveda and the Aveda network of salons, spas and institutes have been raising funds for clean water through a multitude of efforts since 1999, raising over $56 million dollars. As an Aveda Lifestyle company, Neroli Salon & Spa along with the Institutes are passionate about living out the charitable efforts set forth by Aveda.
Supported by staff from The Water Council, Neroli and the Aveda Institutes' Green Teams, student ambassadors who educate their fellow students on how to live greener lives and embody the Aveda Mission, raised funds in support of the Future Water Leaders Fund. Wisconsin post-secondary students working on water tech innovations were invited to apply to the scholarship, which was open from Sept. 5 to Oct. 6, with the Green Teams selecting this year's winners.
"Our students are passionate about clean water access in our community. Members of our institutes' Green Team and administration sought local projects that contribute to research and technology in freshwater," stated Kari Kennedy, director of The Institute of Beauty and Wellness and Aveda Institute Madison. "We are happy to support The Water Council in helping fund the next generation of research in freshwater science."
The 2019 Future Water Leaders Fund winners include:
Basil Hable and Andrew Thompson, University of Wisconsin-Milwaukee (UWM)
Low-Cost Fast-Data Particle Sensor for Harbor Monitoring
The UWM team has developed a low-cost fast-data particle sensor prototype that has potential to capture data throughout the area of a harbor, water treatment center, or other water system for use in data collection in smart cities. As an outcome of this research project, the team will be able to prepare a poster and student's paper, which will be presented at the OCEANS 2020 Conference in Singapore.
Max Spehlmann, University of Wisconsin-Milwaukee School of Freshwater Sciences
Linking Water Age to Bacterial Growth in a Tap Water Distribution System
The proposed research project will pave the way for future water aging studies and help fill a wide knowledge gap in tap water research.
"We are pleased to partner once again with Neroli Salon & Spa, Aveda Institute Madison and The Institute of Beauty and Wellness for this round of the Future Water Leaders Fund," stated Karen Frost, vice president of economic development for The Water Council. "This project funding will support the next generation water researchers and talent, and advance research projects and efforts to impact clean water."
People: Andrew Thompson, Basil Hable, Karen Frost, Kari Kennedy, Max Spehlmann
Organizations: Green Team, The Water Council
Recent Press Releases by The Water Council
Nov 5th, 2019 by The Water Council
Miltrim Farms Inc. becomes first farm in North America to achieve water stewardship certification
Oct 25th, 2019 by The Water Council
Additional farms being recruited to participate in Clear Water Farms program
The Water Council now accepting applications for fifth round of Pilot Program
Sep 23rd, 2019 by The Water Council
The program connects water-related businesses with potential sites and funding to further validate and commercialize technologies.

redpajama_set_name: RedPajamaCommonCrawl


text:
The Effect of Route of Administration on the Cimetidine‐Theophylline Drug Interaction
Karl F. Cremer, John Secor, K. V. Speeg
Joe R & Teresa Lozano School of Medicine
The effect of route of cimetidine administration on cimetidine‐mediated inhibition of theophylline oxidation was examined in healthy individuals. Based on the evidence that cimetidine‐mediated inhibition of drug oxidation is competitive and, therefore, dependent on cimetidine concentration in the liver, oral cimetidine was tested to determine whether it would cause greater inhibition of drug oxidation than intravenous (IV) cimetidine. Both oral and IV cimetidine decreased theophylline clearance to the same extent. However, when clearance was corrected for cimetidine AUC, oral cimetidine resulted in a greater inhibition than IV cimetidine. Thus, the potential for increased inhibitory effect of oral cimetidine was balanced by decreased absorption after oral administration. Degree of inhibition (absolute change in theophylline clearance) and percent of inhibition after cimetidine correlated with the basal theophylline clearance. Individuals with higher basal theophylline clearances had greater degree and percent of inhibition than individuals with lower basal theophylline clearances. 1989 American College of Clinical Pharmacology
The Journal of Clinical Pharmacology
https://doi.org/10.1002/j.1552-4604.1989.tb03361.x
10.1002/j.1552-4604.1989.tb03361.x
Dive into the research topics of 'The Effect of Route of Administration on the Cimetidine‐Theophylline Drug Interaction'. Together they form a unique fingerprint.
Cimetidine Medicine & Life Sciences 100%
Drug Interactions Medicine & Life Sciences 81%
Theophylline Medicine & Life Sciences 56%
Clinical Pharmacology Medicine & Life Sciences 10%
Oral Administration Medicine & Life Sciences 7%
Pharmaceutical Preparations Medicine & Life Sciences 6%
Area Under Curve Medicine & Life Sciences 6%
Cremer, K. F., Secor, J., & Speeg, K. V. (1989). The Effect of Route of Administration on the Cimetidine‐Theophylline Drug Interaction. The Journal of Clinical Pharmacology, 29(5), 451-456. https://doi.org/10.1002/j.1552-4604.1989.tb03361.x
The Effect of Route of Administration on the Cimetidine‐Theophylline Drug Interaction. / Cremer, Karl F.; Secor, John; Speeg, K. V.
In: The Journal of Clinical Pharmacology, Vol. 29, No. 5, 05.1989, p. 451-456.
Cremer, KF, Secor, J & Speeg, KV 1989, 'The Effect of Route of Administration on the Cimetidine‐Theophylline Drug Interaction', The Journal of Clinical Pharmacology, vol. 29, no. 5, pp. 451-456. https://doi.org/10.1002/j.1552-4604.1989.tb03361.x
Cremer KF, Secor J, Speeg KV. The Effect of Route of Administration on the Cimetidine‐Theophylline Drug Interaction. The Journal of Clinical Pharmacology. 1989 May;29(5):451-456. https://doi.org/10.1002/j.1552-4604.1989.tb03361.x
Cremer, Karl F. ; Secor, John ; Speeg, K. V. / The Effect of Route of Administration on the Cimetidine‐Theophylline Drug Interaction. In: The Journal of Clinical Pharmacology. 1989 ; Vol. 29, No. 5. pp. 451-456.
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title = "The Effect of Route of Administration on the Cimetidine‐Theophylline Drug Interaction",
abstract = "The effect of route of cimetidine administration on cimetidine‐mediated inhibition of theophylline oxidation was examined in healthy individuals. Based on the evidence that cimetidine‐mediated inhibition of drug oxidation is competitive and, therefore, dependent on cimetidine concentration in the liver, oral cimetidine was tested to determine whether it would cause greater inhibition of drug oxidation than intravenous (IV) cimetidine. Both oral and IV cimetidine decreased theophylline clearance to the same extent. However, when clearance was corrected for cimetidine AUC, oral cimetidine resulted in a greater inhibition than IV cimetidine. Thus, the potential for increased inhibitory effect of oral cimetidine was balanced by decreased absorption after oral administration. Degree of inhibition (absolute change in theophylline clearance) and percent of inhibition after cimetidine correlated with the basal theophylline clearance. Individuals with higher basal theophylline clearances had greater degree and percent of inhibition than individuals with lower basal theophylline clearances. 1989 American College of Clinical Pharmacology",
author = "Cremer, {Karl F.} and John Secor and Speeg, {K. V.}",
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AU - Cremer, Karl F.
AU - Secor, John
AU - Speeg, K. V.
N2 - The effect of route of cimetidine administration on cimetidine‐mediated inhibition of theophylline oxidation was examined in healthy individuals. Based on the evidence that cimetidine‐mediated inhibition of drug oxidation is competitive and, therefore, dependent on cimetidine concentration in the liver, oral cimetidine was tested to determine whether it would cause greater inhibition of drug oxidation than intravenous (IV) cimetidine. Both oral and IV cimetidine decreased theophylline clearance to the same extent. However, when clearance was corrected for cimetidine AUC, oral cimetidine resulted in a greater inhibition than IV cimetidine. Thus, the potential for increased inhibitory effect of oral cimetidine was balanced by decreased absorption after oral administration. Degree of inhibition (absolute change in theophylline clearance) and percent of inhibition after cimetidine correlated with the basal theophylline clearance. Individuals with higher basal theophylline clearances had greater degree and percent of inhibition than individuals with lower basal theophylline clearances. 1989 American College of Clinical Pharmacology
AB - The effect of route of cimetidine administration on cimetidine‐mediated inhibition of theophylline oxidation was examined in healthy individuals. Based on the evidence that cimetidine‐mediated inhibition of drug oxidation is competitive and, therefore, dependent on cimetidine concentration in the liver, oral cimetidine was tested to determine whether it would cause greater inhibition of drug oxidation than intravenous (IV) cimetidine. Both oral and IV cimetidine decreased theophylline clearance to the same extent. However, when clearance was corrected for cimetidine AUC, oral cimetidine resulted in a greater inhibition than IV cimetidine. Thus, the potential for increased inhibitory effect of oral cimetidine was balanced by decreased absorption after oral administration. Degree of inhibition (absolute change in theophylline clearance) and percent of inhibition after cimetidine correlated with the basal theophylline clearance. Individuals with higher basal theophylline clearances had greater degree and percent of inhibition than individuals with lower basal theophylline clearances. 1989 American College of Clinical Pharmacology
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text:
Q: Attachment download from Gmail While downloading attachments received along with Gmail, attachment are downloaded directly to desktop. I want to download attachment to specific folder I have created in my laptop.

A: You can simply change your default download directory in Google-Chrome.
Go to Settings > Advanced Settings Under Downloads , change your download location to wherever you want.

A: I think chrome does not have an option to download attachments only to a separate folder. I have not seen any such extensions also. The nearest possible solutions are:

*

*Change the download directory of your browser - But other files will also be downloaded to the same location.

*Right-click on the attachment and click save link as and select your directory - You have to choose the directory each time when you are downloading an attachment.

*Use an email program like MS Outlook or Mozilla Thunderbird. These allow you to save your attachments to a specific folder.


been developed via Agrobacteriun tumefaciens in order to study their in planta potential to confer biotic and abiotic resistance as a means of plant breeding. Our results provide new insights into catalytic and structural diversity of GSTs and the detoxifying mechanism used by P. vulgaris. Moreover, highlight the functional and catalytic diversity of plant GSTs and demonstrate their pivotal role for addressing biotic stresses in P. vulgaris.