Possible Mechanisms of Influence of Various Concentrations of Acetylcholine on Hippocampal Functioning

Analysis of features of influence of acetylcholine on the hippocampal functioning was performed basing on the modulation rules for the efficacy of excitatory and inhibitory synaptic transmission we earlier proposed, and also on the known data about location of pre- and postsynaptic muscarine and nicotinic receptors. According to these rules, activation of postsynaptic muscarine М1/М3 and nicotinic receptors should promote long-term potentiation of excitatory and depressions (LTD) of inhibitory input to a neuron, whereas action on М2/М4 receptors should promote LTD of excitatory input and a decrease in neuromodulator release. If inhibitory input is stronger than excitatory, LTP (LTD) of excitatory input to the interneuron should promote LTD (LTP) of excitatory input to a target cell. It follows from the proposed mechanism that a lowing concentration of acetylcholine in the hippocampus, a decrease in density of М1/ М3 and a4p2 receptors, and augmenting binding of М2 receptors must lead to a depression of responses of pyramidal neurons in СА3 and СА1 fields to signals from the entorhinal cortex. Thereof, interaction of the semantic information, stored in the cortex, with the information of an episode-, stored in the hippocampus must be hindered and this effect can underlie disturbances of recall of stored information at Alzheimer’s disease.