Biology subjects

Pearce, R. A.

Publications and source records attributed to Pearce, R. A..

3 recordsLinked to original sources

bioRxiv2025

Dynamic encoding of valence by the anterior cingulate cortex in mice

Fear supports survival by linking environmental cues with potential threats, but its dysregulation contributes to anxiety disorders and PTSD. While the contributions of hippocampus and amygdala to fear memory are well established, the role of the anterior cingulate cortex (ACC) during and after acquisition remains less clear. Here we longitudinally recorded ACC neuronal activity using single-photon calcium imaging in freely behaving mice undergoing auditory fear conditioning. During cue pre-exposure, neural responses to the cue were strongest to early novel presentations and declined with repetition. During acquisition, responses emerged late in training as the cue became shock-predictive. Ensemble analysis identified subpopulations of "freezing on" and "freezing off" cells in the ACC whose activation coincided with decreased neural activity and increased neural synchrony. During 24-h and 48-h recall, ACC responses were robust to early presentations but diminished during late tones; similarly, a subpopulation of neurons emerged that was upmodulated by the CS in early 24-h and 48-h recall. Together, our results demonstrate that ACC neuronal response to a cue reorganizes both within and across sessions, with dynamic changes in population activity, recruitment, and synchrony that mirror changes in novelty and negative valence. This pattern suggests a role for ACC as a flexible hub that dynamically represents changes in cue significance.

neuroscience↗

bioRxiv2022

Chronic intermittent propofol attenuates surgery-induced neuroinflammation, apoptosis, and cognitive impairment in aged mice

Surgery may lead to long-lasting cognitive deficits that are referred to as perioperative neurocognitive disorder (NCD), particularly in elderly patients. Currently, no interventions are routinely employed in clinical practice to prevent perioperative NCD. Here we show that perioperative chronic intermittent administration of propofol to aged mice undergoing laparotomy under isoflurane anesthesia effectively blocks the surgery-induced increase in nitrosative stress, increased expression of proapoptotic proteins, microglial activation, and cognitive deficits. By contrast, in the absence of surgery and anesthesia, propofol had little effect on biochemical parameters and led to cognitive improvement only in a subset of behavioral paradigms. The actions of propofol were largely absent in mice lacking the GABAA receptor 5-subunit, indicating that they are mediated by 5-containing GABAA receptors. These results demonstrate that propofol - via 5-containing GABAA receptors that are redistributed to the cell surface membranes in a sustained manner - can attenuate surgery-induced neuroinflammation and postsurgical cognitive deficits.

neuroscience↗

bioRxiv2022

Dose-dependent suppression of hippocampal contextual memory formation, place cells, and spatial engrams by the NMDAR antagonist (R)-CPP

A common way to study the functional importance of N-methyl-D-aspartate receptors (NMDARs) in hippocampal memory-encoding circuits is by administering NMDAR antagonists. We recently compared the effects of (R,S)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), a competitive NMDAR antagonist, on suppression of memory in vivo versus suppression of NMDAR-mediated field EPSPs (fEPSPNMDA) and long-term potentiation (LTP) in vitro. Surprisingly, we found that concentrations that block contextual conditioning in vivo are ineffective at blocking the fEPSPNMDA or LTP in vitro. Here we tested one possible explanation for the mismatch - that the hippocampus is relatively resistant to CPP compared to other brain structures engaged in contextual fear conditioning. We used the context pre-exposure facilitation effect (CPFE) paradigm to isolate the hippocampal component of contextual learning, and in-vivo calcium imaging of place cells and spatial engrams to directly assess hippocampal spatial coding. We found that, by both measures, the active enantiomer (R)-CPP did interfere with hippocampal function at concentrations below those that block fEPSPs or LTP. We conclude that the alternative - that CPP interferes with memory by targeting NMDARs in interneurons rather than pyramidal neurons - is the more likely explanation.

neuroscience↗