Neural circuits and mechanisms of context specific conditioned inhibition

点击翻译按钮获取中文摘要

The abilities to learn and remember constitute two important functions mediated by the mammalian brain.  One fundamental learning and memory function that most organisms possess is the ability to discriminate between different cues and contexts.  Of particular interest is the demonstration that during discrimination learning, reinforced cues acquire excitatory and non-reinforced cues acquire inhibitory associations.***     We have been investigating these learning processes in rats using a visual discrimination paradigm (VDP).  We demonstrated that successful performance of this instrumental task requires the rat to learn an excitatory association between a particular stimulus and a motor response that is repeatedly reinforced, this behaviour was not context-specific, and was dependent on dorso-lateral striatum.  We also showed that an inhibitory association to the non-reinforced cue was acquired, showed context-specificity, and was dependent on the ventral hippocampus (VH).***     The goal of this proposed research program is to develop a clear understanding of the neural circuits and neural mechanisms necessary for context-specific conditioned inhibition.  Our hypothesis is that a neural circuit encompassing the VH and nucleus accumbens core (NAc) is essential.  We will use various levels of analysis to provide evidence that the VH and NA are a functional circuit mediating context-specific inhibition.  These techniques will include the use of selective neurotoxic lesions or reversible lesions to demonstrate a functional interaction between the VH and NAc.  We will also evaluate information processing in VH and NAc during acquisition of the VDP.  This will be achieved using high density, multi-site electrophysiological recording techniques in freely-behaving rats.  Finally, we will investigate the neurochemical basis of the context-specific inhibition effect.  This aim will be achieved by blocking neurotransmitter systems in the VH or NAc during discrimination learning. ***Impact:  There has been an impressive scholarly effort and tradition of trying to account for how behaviour is shaped by exposure to specific events and environmental conditions and the neural systems responsible.  This undertaking has made many advances in our understanding of the conditions and mechanisms of learning in human and non-human animals and has had a huge impact on modern society.  For example, this work is revolutionizing our understanding of the nature and causes of psychiatric disorders including addiction, anxiety, post-traumatic stress disorder, and obesity.  Despite these and other contributions, many important issues concerning conditioning processes remain unknown.  Different forms of inhibitory conditioning, their neural substrates and biochemical mechanisms mediating them are not well understood and there is still significant room for discovery, innovation and impact in this area of basic research.********