Neurons are necessary for all connections made in the brain, and thus can be thought of as the "wires" of the brain. As in computing, an entity is most efficient when its wires are optimized; therefore, a brain which has undergone millions of years of natural selection would be expected to have optimized neural circuitry. To have an optimized neural system it must balance four variables—it must "minimize conduction delays in axons, passive cable attenuation in dendrites, and the length of 'wire' used to construct circuits" as well as "maximize the density of synapses", essentially optimizing the neuropil. Researchers at Cold Spring Harbor Laboratory formulated the optimal balance of the four variables and calculated the optimal ratio of axon plus dendrite volume (i.e. the "wire" volume or neuropil volume) to total volume of grey matter. The formula predicted an optimal brain with 3/5 (60%) of its volume occupied by neuropil. Experimental evidence taken from three mouse brains agrees with this result. The "fraction of wire is 0.59 ± 0.036 for layer IV of visual cortex, 0.62 ± 0.055 for layer Ib of piriform cortex, and 0.54 ± 0.035 for the stratum radiatum of hippocampal field CA1. The overall average is 0.585 ± 0.043; these values are not statistically different from the optimal 3/5." It has been shown that a certain protein is lost in people with schizophrenia that causes dendrites and spines to deteriorate in the dorsolateral prefrontal cortex, a part of the neocortex, which plays a key role in information processing, attention, memory, orderly thinking and planning which are all functions that deteriorate in people with schizophrenia. The deterioration of the neuropil in this cortex has been proposed as the cause of schizophrenia. Alzheimer's is a neuropathological disease that is hypothesized to result from the loss of dendritic spines and/or deformation of these spines in the patient's frontal and temporal cortices. Researchers have tied the disease to a decrease in the expression of drebrin, a protein thought to play a role in long-term potentiation, meaning the neurons would lose plasticity and have trouble forming new connections. This malfunction presents itself in the form of helical filaments that tangle together in the neuropil. This same phenomenon seems to occur in the elderly as well. A significant non-human area of neuropil is the barrel cortex found in mammals with whiskers (e.g. cats, dogs and rodents); each "barrel" in the cortex is a region of neuropil where the input from a single whisker terminates.