Exogenously applied opioids activate a postsynaptic potassium conductance, in many neurons, including the Im164647. However, while exogenously applied agonists inform us of what to expect when individuals are administered an opioid drug such as morphine, this method provides limited insight into how the endogenous opioid system functions. This study is the first example of endogenously released opioids, or in fact any endogenously released neuropeptide, activating a potassium conductance. The resulting membrane hyperpolarization would be expected to increase the excitatory synaptic input required to produce postsynaptic action potentials. In addition, the lower membrane resistance would likely shunt synaptic inputs from more distal synapses and thus could reduce the ability of all excitatory synaptic inputs to produce postsynaptic action potentials (Fig. 7a). This scenario would be particularly important if enkephalins are acting at the large dendrites we observed to be associated with ME immunereactive terminals (Fig. 4a). These additional roles for endogenous opioids as regulators of postsynaptic excitability and membrane resistance would be expected to have a widespread effect on information flow through the Im. Indeed, it is feasible that endogenously released opioids could limit the impact of all synaptic inputs on the membrane potential of Im neurons and thus alter feed-forward signalling in this neural circuit. This is in contrast to previous studies that describe endogenous opioid actions that are limited to inhibiting pre-synaptic inputs that express opioid receptors1314. This is the first instance in which endogenous opioids have been shown to influence postsynaptic neuronal excitability, which in turn would be expected to alter the neuronal response to synaptic inputs.