(346ag) Computational Modeling to Understand the Spatiotemporal Cholinergic Modulation of Hippocampal Synaptic Plasticity

In septohippocampal cultures, stimulating the Schaffer collateral to CA1 pyramidal neuron synapse while optogenetically stimulating the stratum oriens (releasing acetylcholine) has been shown to induce long term potentiation, short term potentiation, and short-term depression mediated through either muscarinic or nicotinic receptors. The type of induced plasticity and the selectivity of receptors is dependent on the relative timing of cholinergic input and Schaffer collateral stimulation. We hypothesize that receptor desensitization is a crucial determinant of the observed receptor selectivity and, therefore, the induction of the specific form of plasticity. The desensitization time of muscarinic and nicotinic receptors have been shown to differ by several orders of magnitude. In this work, we develop a physiologically relevant computational modeling framework to investigate how the temporal activation of the Shaffer collateral-CA1 pyramidal neuron synapse with cholinergic inputs impacts the specific receptors type deactivation and leads to the induction of the particular form of synaptic plasticity mediated through different types of cholinergic receptors. We find that the desensitization time impacts the induction of a particular form of plasticity by altering the intracellular calcium transients. Our findings elucidate the effects of neuromodulation on the synaptic plasticity through receptor desensitization and describe how temporal activation of cholinergic inputs modulate the synaptic connections in the hippocampus.