Posterior parietal cortex mediates fear renewal in a novel context

Abstract

The return of fear following extinction therapy is an important issue associated with the treatment of many fearrelated disorders. Fear renewal is a suitable model, with which context-dependent modulation of the fear response can be examined. In this model, any context outside of an extinction context (e.g., novel or familiar contexts) could evoke relapse of the fear response. However, brain regions associated with context-dependent modulation are not fully understood. The posterior parietal cortex (PPC) is considered a center for integrating multisensory information and making decisions. To study its role in the contextual modulation of fear relapse, we reversibly inactivated the PPC in mice before they were exposed to various contexts after extinction training. When muscimol was infused into the PPC, fear renewal was impaired in a novel context, but not in a familiar context. Fear relapses were blocked during optogenetic inhibition of the PPC, only when animals were placed in a novel context. We propose that the neural activity of the PPC is necessary for the relapse of a precise response to an extinguished conditioned stimulus in a novel context.

Comparative metabolic profiling of posterior parietal cortex, amygdala, and hippocampus in conditioned fear memory

“…Some studies have investigated the metabolites and pathways that are differentially regulated in the prefrontal cortex and nucleus accumbens as well as AMG and HPC in social defeat stress and chronic restraint stress models of mental disorders [34,42]. Although the PPC is implicated in fear learning and memory [29,43], the metabolites and metabolic pathways that are affected in PPC remain unknown. In our study, UPLC-MS/MS based metabolomics analysis data showed that purine metabolism, pantothenate and CoA biosynthesis, glutathione metabolism, and NAD + -dependent signaling were the most perturbed pathways in retrieval of conditioned fear memory.…”

“…The fear conditioning procedure was performed in accordance with a previous protocol [43]. For the retrieval test, the context and day conditions of the procedure were modi ed because fear extinction training was not required.…”

Memories are not written in stone: Re-writing fear memories by means of non-invasive brain stimulation and optogenetic manipulations

“…Similarly, adeno-associated virus carrying halorhodopsin was injected 3 weeks before behavioral training into the posterior parietal cortex (PPC) (Joo et al, 2020), which receives diverse sensory and cognitive inputs (Andersen and Buneo, 2002;Morcos and Harvey, 2016;Raposo et al, 2014) and integrates multisensory signals (Andersen and Buneo, 2002;Najafi and Churchland, 2018;Song et al, 2017). Sensory information is processed by the PPC and transformed into behavioral outcomes.…”

A cortical cell ensemble in the posterior parietal cortex controls past experience-dependent memory updating

“…Recent findings indicate that the PPC plays important role in memory updating. The PPC modulates fear memory renewal after the extinction in fear conditioning 19 . The PPC represents past sensory history and influences behavioral outcomes upon current experience 20 .…”