Jordan Chambers, Shihab Shamma, Anthony Burkitt, David Grayden, Diego Elgueda, Jonathan FritzNeurons in the primary auditory cortex (A1) display rapid task-related plasticity, which is believed to enhance the ability to selectively attend to one stream of sound in complex acoustic scenes. Previous studies have suggested that cholinergic projections from Nucleus Basalis to A1 modulate auditory cortical responses and may be a key component of rapid task related plasticity. However, the underlying molecular, cellular and network mechanisms of cholinergic modulation of cortical processing remain unclear.A previously published model of A1 receptive fields [1] that can reproduce task-related plasticity was used to investigate mechanisms of cholinergic modulation in A1. The previous model comprised a cochlea model and integrate- and-fire model neurons to represent networks in A1. Action potentials from individual model neurons were used to calculate the receptive field using reverse correlation, which allowed direct comparison to experimental data. To allow an investigation into different mechanisms of cholinergic modulation at A1, this previous model was extended by: (1) adding integrate-and-fire neurons to represent neurons projecting from Nucleus Basalis to A1; (2) adding inhibitory interneurons in A1; (3) including internal calcium dynamics in the integrate-and-fire models; and (4) including calcium-dependent potassium conductance in the integrate-and-fire models. Since cholinergic modulation has several potential sites of action in A1, the current model was used to investigate acetylcholine acting through both muscarinic and nicotinic acetylcholine receptors (mAChR and nAChR, respectively) located presynaptically or postsynaptically.Four possible mechanisms of cholinergic modulation on A1 receptive fields were investigated. Previous research indicates cholinergic modulation should be able to suppress an inhibitory region and enhance an excitatory region in the receptive fields [2]. Our model indicates it is unlikely that any one of these four mechanisms could produce these opposite changes to both excitatory and inhibitory regions. However, multiple mechanisms occurring simultaneously could produce the expected changes to the receptive fields in this model. We demonstrate that combining either presynaptic nAChR with presynaptic mAChR or presynaptic nAChR with postsynaptic nAChR is capable of producing changes to A1 receptive fields observed during rapid task-related plasticity.This model tested four mechanisms by which cholinergic modulation may induce rapid task-related plasticity in A1. Cholinergic modulation could reproduce experimentally observed changes to A1 receptive fields when it was implemented using a combination of mechanisms. Two different combinations of cholinergic modulation were found to produce the expected changes in A1 receptive fields. Since the model predicts that these two different combinations of cholinergic modulation would have differential effects on the rate of neuronal firing, it will be possible to run experimental tests to distinguish between the two theoretic possibilities.References[1] Chambers JD, Elgueda D, Fritz JB, Shamma SA, Burkitt AN, Grayden DB: **Computational neural modeling of Auditory Cortical Receptive Fields**. _Front Comput Neurosci_ 2019, 13:28. Epub 2019/06/11.[2] Fritz J, Shamma S, Elhilali M, Klein D: **Rapid task-related plasticity of spectrotemporal receptive fields in primary auditory cortex**. _Nat Neuroscience_ 2003, 6(11):1216-23.
