promotion of coordinated firing of adjacent axons and the promotion of rhythmic activity in structures such as the hippocampus when ACh is released and levels are high may provide an increase in the baseline excitability of neurons that are then available for robust responses to glutamate, and this state dependent facilitation of neurotransmission in pathways activated in response to ACh release is likely to be maintained due to facilitated neuronal plasticity. This organization is echoed in the hypothalamus where, despite the ubiquitous expression of nAChRs on multiple neuronal subtypes with reciprocal functions, the kinetics of activation of one set of receptors may bias the output in one direction, based on the starting conditions. This is obviously a gross oversimplification that will be sensitive to the timing, duration and localization of ACh signaling, but may provide a framework for generation of hypotheses. Finally, increases in ACh signaling appear to contribute to stress-related illnesses such as major depressive disorder, although the specific neuronal substrates and cellular mechanisms responsible for these effects are only beginning to be studied.
