Biology subjects

Agee, L. A.

Publications and source records attributed to Agee, L. A..

3 recordsLinked to original sources

bioRxiv2024

Extinction Training Suppresses Activity of Fear Memory Ensembles Across the Hippocampus and Alters Transcriptomes of Fear-Encoding Cells

Contextual fear conditioning has been shown to activate a set of "fear ensemble" cells in the hippocampal dentate gyrus (DG) whose reactivation is necessary and sufficient for expression of contextual fear. We previously demonstrated that extinction learning suppresses reactivation of these fear ensemble cells and activates a competing set of DG cells - the "extinction ensemble." Here, we tested whether extinction was sufficient to suppress reactivation in other regions and used single nucleus RNA sequencing (snRNA-seq) of cells in the dorsal dentate gyrus to examine how extinction affects the transcriptomic activity of fear ensemble and fear recall-activated cells. Our results confirm the suppressive effects of extinction in the dorsal and ventral dentate gyrus and demonstrate that this same effect extends to fear ensemble cells located in the dorsal CA1. Interestingly, the extinction-induced suppression of fear ensemble activity was not detected in ventral CA1. Our snRNA-seq analysis demonstrates that extinction training markedly changes transcription patterns in fear ensemble cells and that cells activated during recall of fear and recall of extinction have distinct transcriptomic profiles. Together, our results indicate that extinction training suppresses a broad portion of the fear ensemble in the hippocampus, and this suppression is accompanied by changes in the transcriptomes of fear ensemble cells and the emergence of a transcriptionally unique extinction ensemble.

neuroscience↗

bioRxiv2022

Patterns of Arc mRNA expression in the rat brain following dual recall of fear- and reward-based socially acquired information

The ability to learn new information and behaviors is a vital component of survival in most animal species. This learning can occur via direct experience or through observation of another individual (i.e., social learning). While research focused on understanding the neural mechanisms of direct learning is prevalent, less work has aimed at understanding the brain circuitry mediating the acquisition and recall of socially acquired information. We aimed to further elucidate the mechanisms underlying recall of socially acquired information by having rats sequentially recall a socially transmitted food preference (STFP) and a fear association via fear conditioning by-proxy (FCbP). Brain tissue was processed for mRNA expression of the immediate early gene (IEG) Arc, which reliably expresses in the cell nucleus following transcription before migrating to the cytoplasm over the next 25 minutes. Given this timeframe, we were able to identify whether Arc transcription was triggered by STFP recall, FCbP recall, or following recall of both memories. Surprisingly - and contrary to past research examining expression of other IEGs following STFP or FCbP recall separately - we found no differences in any of the Arc expression measures across a number of prefrontal regions and the vCA3 of the hippocampus between controls, demonstrators, and observers, though we did detect an overall effect of sex in a number of regions. We theorize that these results may indicate that relatively little Arc-dependent neural restructuring is taking place in the prefrontal cortices following recall of a recently socially acquired information or directly acquired fear associations in these areas.

neuroscience↗

bioRxiv2021

Expression patterns of Arc mRNA after renewal of appetitive behavior in female rats.

Renewal of appetitive behavior depends on the gonadal hormonal state of the female rat. In this experiment the effect of female rat estrous cycle stage on renewal of appetitive behaviors is replicated and extended upon to understand how endogenous hormonal states around the estrous cycle drive renewal at the neuronal population level. Estrous cycle stage (i.e., proestrus (P, high hormone) or metestrus/diestrus (M/D, low hormone)) was considered during two important learning and behavioral expression windows: at extinction training and during LTM/renewal testing. First, rats in P during context-dependent extinction training but in some other stage of the estrous cycle during long-term memory and renewal testing (Different) were shown to exhibit more renewal of conditioned foodcup (but not conditioned orienting) behavior compared to rats in other estrous cycle groups. Next, cellular compartment analysis of temporal activity using fluorescence in situ hybridization (catFISH) was used to examine immediate early gene activity of Arc mRNA in neuronal populations after distinct context-stimulus exposures (i.e., extinction and acquisition test contexts). Arc mRNA expression patterns were examined in the prefrontal cortex (PFC), amygdala, hippocampus (HPC), and paraventricular nucleus of the thalamus. P-different rats showed differential neuronal population activity in the infralimbic cortex of the PFC, the lateral amygdaloid nucleus, and both CA1 and CA3 regions of the dorsal HPC. In each region P-different rats exhibited more co-expression and less specificity of Arc mRNA compared to other hormonal groups, indicating that renewal of appetitive foodcup behavior induces Arc mRNA in overlapping neuronal populations in female rats.

animal behavior and cognition↗