Extinction of Cocaine Memory Depends on a Feed-Forward Inhibition Circuit Within the Medial Prefrontal Cortex

Abstract

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GIRK channel activity in prelimbic pyramidal neurons regulates the extinction of cocaine conditioned place preference in male mice

“…While GIRK channel ablation did not impact the acquisition of cocaine CPP, the manipulation impaired extinction in male, but not female, mice. This finding aligns with a recent report demonstrating that chemogenetic inhibition of a local GABAergic interneuron population in the dorsal mPFC (dmPFC, which includes the PL and anterior cingulate cortex) impaired the extinction of cocaine CPP in male mice 12 . These results support the contention that inhibitory signalling in adjacent PL pyramidal neurons, including perhaps GIRK‐dependent signalling, is necessary for the extinction of cocaine CPP in male mice.…”

“…This finding aligns with a recent report demonstrating that chemogenetic inhibition of a local GABAergic interneuron population in the dorsal mPFC (dmPFC, which includes the PL and anterior cingulate cortex) impaired the extinction of cocaine CPP in male mice. 12 These results support the contention that inhibitory signalling in adjacent PL pyramidal neurons, including perhaps GIRK-dependent signalling, is necessary for the extinction of cocaine CPP in male mice. Interestingly, chronic exposure to stress delayed the extinction of opioid-induced CPP in male mice 34 and, similar to repeated cocaine exposure, suppressed GABA B R-dependent signalling in PL pyramidal neurons in male and female mice.…”

“…This finding aligns with clinical and preclinical work to support the notion that postsynaptic inhibitory signalling in PL pyramidal neurons can drive extinction learning. For example, GABAergic signalling in the human dorsal anterior cingulate cortex, 40 as well as the homologous rodent PL, 12,41,42 has been suggested to initiate extinction learning in male subjects. Preclinical studies have also shown that systemic delivery of baclofen accelerated the extinction of CPP evoked by methamphetamine and morphine in male rodents 34,43,44 .…”

The disruption of white matter integrity of systemic striatal circuits in alcohol‐dependent males with physiological cue reactivity

“…Behaviourally, inhibitory control impairment is linked to heightened sensitivity to alcohol reward 49 . Inhibitory control circuitry involves frontal regions, including the dlPFC, vlPFC and SMA 50–52 . Thus, the dlPFC has been a frequent target for transcranial magnetic stimulation and transcranial direct current stimulation to reduce cue‐related craving 53,54 .…”

Theta coupling within the medial prefrontal cortex regulates fear extinction and renewal

“…More specifically, the prelimbic cortex (PL) has been shown to predominantly drive fear expression ( Burgos-Robles et al., 2009 ; Corcoran and Quirk, 2007 ; Kim et al., 2013 ; Sharpe and Killcross, 2015 ), whereas the infralimbic cortex (IL) regulates the extinction of learned fear ( Milad and Quirk, 2002 ; Quirk and Mueller, 2008 ; Sierra-Mercado et al., 2011 ; Vidal-Gonzalez et al., 2006 ; Lebron et al., 2004 ). However, this idea of the segregated function of the PL and IL has recently been challenged as direct synaptic inter-connectivity between these regions affects the extinction of fear ( Marek et al., 2018 ; Mukherjee and Caroni, 2018 ) and cocaine seeking ( Visser et al., 2022 ). A wealth of research has explored the roles of individual mPFC subregions at specific time points during fear and extinction, but the nature of network activity within the PL and IL during fear learning, expression, extinction, and fear relapse are not fully understood.…”