Biology subjects

Taylor, W. W.

Publications and source records attributed to Taylor, W. W..

3 recordsLinked to original sources

bioRxiv2026

Adolescent blockade of complement signaling in the lateral septum increases social novelty seeking behavior in male mice

Social behaviors are critical for survival and change dramatically over the lifespan. Adolescence is a critical period of development during which social novelty seeking peaks before declining into adulthood. Adolescence is also a time of pronounced neural circuit refinement as excess synapses are eliminated. One critical mechanism supporting this maturation of neural circuits is microglial pruning of synapses through the classical complement signaling cascade. However, it remains unclear how microglial pruning of the neural circuitry supporting social novelty preference shapes the trajectory of this behavior during adolescence. To address this, we blocked microglial complement-dependent pruning during adolescence by injecting neutrophil inhibitory factor (NIF; blocks the adhesion of ligands to CD11b/C3 receptor) in the lateral septum (LS), a key node in the social circuitry supporting social novelty preference, in male mice. We found that NIF administration into the LS during adolescence increased preference for the novel social chamber over the familiar as compared to control PBS administration. LS-NIF treatment had no impact on anxiety-like behavior in the light-dark box test and no effect on sociability. LS-NIF treatment also decreased the expression of immune-related genes in the LS as compared to PBS treatment. These data support the hypothesis that complement-dependent microglial synaptic elimination in the LS is critical for the developmental progression of social novelty preference.

neuroscience↗

bioRxiv2025

Ensembles and engrams in mouse cortical and sub-thalamic brain regions supporting context and memory recall.

Associative learning supports learning about outcomes associated with contexts and cues. During learning, cellular ensembles that become active can be incorporated into a memory engram and later reactivated to support memory recall. Studies exploring engram formation and reactivation have primarily used contextual conditioning in mice and made little distinction between engrams encoding contextual information versus cue-associated learning and recall. Furthermore, often missing in such analyses is exploration of sex differences in engram profiles. Using auditory fear conditioning and activity-dependent tagging in mice, we set out to disaggregate context-associated engrams from those associated with learning and recall while also profiling potential sex differences. Specifically, we quantified cellular activity during context exposure, fear recall, extinction training, and extinction recall in cortical and subthalamic brain regions supporting learning and memory. We found that male mice had larger ensembles of cells active in the infralimbic prefrontal cortex (IL-PFC) during context exposure while female mice recalling a fear memory had a significantly greater proportion of cells that were active in the IL-PFC independent of context. Across sexes, we found greater reactivation of extinction engrams in the IL-PFC compared to contextual engrams. While we found ensembles and engrams in the prelimbic prefrontal cortex (PL-PFC) and zona incerta (ZI), no sex differences were noted in these regions. These results not only emphasize that there is a distinction to be made between ensembles and engrams encoding contextual information from those encoding cue-associated learning and recall, but also highlight sex differences in ensemble and engram allocation.

neuroscience↗

bioRxiv2020

Sex-specific calibration of memory recall by glucocorticoid receptors on cortical astrocytes

Dysfunctions in memory recall lead to pathological fear; a hallmark of trauma-related disorders, like Post-Traumatic Stress Disorder (PTSD). Heightened recall of an association between a cue and trauma, as well as impoverished recall that a previously trauma-related cue is no longer a threat both result in a debilitating fear toward the cue. Glucocorticoid-mediated action via the glucocorticoid receptor (GR) influences memory recall. This literature has primarily focused on GRs expressed in neurons or ignored cell-type specific contributions. To ask how GR action in non-neuronal cells influences memory recall, we combined auditory fear conditioning in mice and the knockout of GRs in astrocytes in the prefrontal cortex (PFC), a brain region implicated in memory recall. We found that GRs in astrocytes in the PFC calibrate recall in female but not male mice. Specifically, we found that knocking out GRs in astrocytes in the PFC of female mice (AstroGRKO) after fear conditioning resulted in higher recall of fear to the CS+ tone when compared to controls (AstroGRintact). While we did not find any differences in extinction of fear toward the CS+ between these groups, AstroGRKO female mice showed impaired recall of extinction training. We did not observe any significant results in male mice. These results suggest a sex-specific calibration of memory recall by GRs in astrocytes in the PFC. These data demonstrate the need to examine GR action in cortical astrocytes to elucidate the basic neurobiology underlying memory recall and potential mechanisms that underlie female-specific biases in the incidence of PTSD.

neuroscience↗