• Thursday, October 5th 2017 at 15:00 - 16:00 UTC (Other timezones)
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Dopaminergic (DA) neurons located in the ventral tegmental area (VTA) signal motivational properties of natural reinforcers and addictive drugs.  Electrophysiological recordings have demonstrated that transient inputs to the VTA, e.g. glutamatergic (Glu) and cholinergic (ACh), convey salient information about the environment. However, how such inputs are converted into the DA output remains under active investigation. Furthermore, how addictive drugs such as nicotine modulate the VTA response to afferent inputs is still to be pinned down. We address these questions using a biologically relevant computational model of the VTA circuitry.  I will present our modelling efforts to understand how specific nicotinic mechanisms within the VTA microciruit structure dopaminergic neurotransmission. I will first show that the model accounts for in vivo and in vitro data obtained during nicotine exposures and manipulations of VTA input structures. We then show that our model can account for nicotine responses to repeated injections in both wild-type and animals where the a4b2 nAChRs are knocked out as well as paradoxical effects of a7 agonists.

Our results clarify biological mechanisms that may translate salient inputs to the VTA into dopamine output and how addictive drugs subvert these signals. Time-permitting I will discuss our on-going work on modelling nicotinic control over resting state activity in the pre-frontal cortex and its implications for disorders such as schizophrenia.

Boris Gutkin, PhD
GNT, ENS Paris
Center for Cognition and Decision Making, Higher School of Economics, Moscow

Boris Gutkin – Nicotine’s nicotinic mechanisms for cholinergic control over dopaminergic circuit dynaimcs (and beyond)

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