PV network plasticity mediated by neuregulin1-ErbB4 signalling controls fear extinction

Paradoxical self-sustained dynamics emerge from orchestrated excitatory and inhibitory homeostatic plasticity rules

“…In contrast, experimental studies both in vitro and in vivo have shown that self-sustained activity emerges autonomously during development ( 21 – 26 ), indicating that synaptic plasticity rules are in place to orchestrate the unsupervised emergence of inhibition-stabilized dynamics. Additionally, because the four weight classes have been observed to undergo synaptic plasticity in experimental studies ( 27 – 32 ), here we ask how inhibition-stabilized dynamics might emerge in a self-organizing manner.…”

Enhancing adult neuroplasticity by epigenetic regulation of Parvalbumin-expressing GABAergic cells

“…Such heightened synaptic remodelling and decreased expression of critical PNN components might contributes to long-term retention of extinction memory. In accordance with this hypothesis, Chen et al 14 showed that extinction learning increased the fraction of PV + cells expressing low PV levels, which are thought to be more plastic 17 . They further showed that chemogenetic-mediated manipulations of PV + cell activity affected mouse freezing during extinction learning, with more active PV + cells leading to higher freezing.…”

“…Third, PV + cell-specific deletion of Nogo Receptor 1, a neuronal receptor for myelin-associated growth inhibitors 12 , enhances both BLA PV + synapse remodeling and the retention of fear extinction 16 . Fourth, fear extinction weakens the functional outputs of PV + cells to pyramidal neurons in medial prefrontal cortex 14 . All together, these data suggest GABAergic PV + cell plasticity, an activity-regulated process [17][18][19] , is required for extinction learning and retention.…”

“…Recent studies showed that PV + cells also play a role in fear memory extinction. First, fear responses during extinction learning are increased by chemogenetic activation of PV + cells in the medial prefrontal cortex 14 . Second, extinction training induces remodelling of perisomatic PV + synapses around excitatory neurons that were previously activated during fear conditioning in the basolateral amygdala (BLA) 15 .…”

Prefrontal GABAA(δ)R Promotes Fear Extinction through Enabling the Plastic Regulation of Neuronal Intrinsic Excitability

“…The mPFC engagement in fear extinction requires the dynamic interplay of a spectrum of neurotransmitters and neuromodulators (Bukalo et al, 2014). Among these, the inhibitory signals mediated by the GABA transmitter and its receptors are generally thought to suppress the extinction of learned fear (Davis and Myers, 2002;Chhatwal et al, 2005;Sierra-Mercado et al, 2011;Marek et al, 2018a;Chen et al, 2022). It was shown that chemogenetically activating the parvalbumin-positive interneurons in the infralimbic (IL) subregion of mPFC diminishes the fear extinction recall (Marek et al, 2018a;Chen et al, 2022).…”