Wednesday 29th March 2017
Ground Floor Seminar Room
25 Howland Street, London, W1T 4JG
Nicotine’s nicotinic mechanisms for control over dopaminergic circuit function (and beyond).
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 did his undergraduate studies in physics and history at the North Carolina State University, followed by a masters in Biomathematics. He received his doctorate from the University of Pittsburgh (Center for Neural Basis of Cognition) where he worked on mathematical models of neural excitability and its neuromodulation. He continued with an NSF Bioinformatics postdoctoral fellowship at the CNRS (France) and the Institut Pasteur and a research fellowship at the Gatsby. Boris Gutkin has been a tenured researcher at the CNRS since 2004 and in 2006 he co-lead the creation of the Group for Neural Theory at Ecole Normale Superieure where he is now one of the team directors. Since 2011 Dr. Gutkin is a Director of Research at the CNRS and now holds a cross-appointment as a visiting professor at the Center for Cognition and Decision Making, Higher School of Economics, Moscow. Dr. Gutkin’s research interests include computational models of neuromodulation and drug addiction, neuronal oscillations and neural dynamics.