Interplay of prefrontal cortex and amygdala during extinction of drug seeking
Abstract
Extinction of Pavlovian conditioning is a complex process that involves brain regions such as the medial prefrontal cortex (mPFC), the amygdala and the locus coeruleus. In particular, noradrenaline (NA) coming from the locus coeruleus has been recently shown to play a different role in two subregions of the mPFC, the prelimbic (PL) and the infralimbic (IL) regions. How these regions interact in conditioning and subsequent extinction is an open issue. We studied these processes using two approaches: computational modelling and NA manipulation in a conditioned place preference paradigm (CPP) in mice. In the computational model, NA in PL and IL causes inputs arriving to these regions to be amplified, thus allowing them to modulate learning processes in amygdala. The model reproduces results from studies involving depletion of NA from PL, IL, or both in CPP. In addition, we simulated new experiments of NA manipulations in mPFC, making predictions on the possible results. We searched the parameters of the model and tested the robustness of the predictions by performing a sensitivity analysis. We also present an empirical experiment where, in accord with the model, a double depletion of NA from both PL and IL in CPP with amphetamine ...Continue Reading
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