Biology subjects

Dias, B. G.

Publications and source records attributed to Dias, B. G..

5 recordsLinked to original sources

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↗

bioRxiv2023

RNA in extracellular vesicles during adolescence reveal immune, energetic and microbial imprints of early life adversity.

Exposure to early life adversity (ELA), including childhood maltreatment, is one of the most significant risk factors for the emergence of neuropsychiatric disorders in adolescence and adulthood. Despite this relationship being well established, the underlying mechanisms remain unclear. One way to achieve this understanding is to identify molecular pathways and processes that are perturbed as a consequence of childhood maltreatment. Ideally, these perturbations would be evident as changes in DNA, RNA or protein profiles in easily accessible biological samples collected in the shadow of childhood maltreatment. In this study, we isolated circulating extracellular vesicles (EVs) from plasma collected from adolescent rhesus macaques that had either experienced nurturing maternal care (CONT) or maternal maltreatment (MALT) in infancy. RNA sequencing of RNA in plasma EVs and gene enrichment analysis revealed that genes related to translation, ATP synthesis, mitochondrial function and immune response were downregulated in MALT samples, while genes involved in ion transport, metabolism and cell differentiation were upregulated. Interestingly, we found that a significant proportion of EV RNA aligned to the microbiome and that MALT altered the diversity of microbiome-associated RNA signatures found in EVs. Part of this altered diversity suggested differences in prevalence of bacterial species in CONT and MALT animals noted in the RNA signatures of the circulating EVs. Our findings provide evidence that immune function, cellular energetics and the microbiome may be important conduits via which infant maltreatment exerts effects on physiology and behavior in adolescence and adulthood. As a corollary, perturbations of RNA profiles related to immune function, cellular energetics and the microbiome may serve as biomarkers of responsiveness to ELA. Our results demonstrate that RNA profiles in EVs can serve as a powerful proxy to identify biological processes that might be perturbed by ELA and that may contribute to the etiology of neuropsychiatric disorders in the aftermath of ELA.

zoology↗

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↗

bioRxiv2019

Proximate causes and consequences of intergenerational influences of salient sensory experience.

Salient sensory environments experienced by a parental generation can exert intergenerational influences on offspring, including offspring not conceived at the time of the parental experience. While these data provide an exciting new perspective on biological inheritance, questions remain about causes and consequences of intergenerational influences of salient sensory experience. We have previously shown that exposing male mice to a salient olfactory experience like olfactory fear conditioning results in offspring demonstrating a sensitivity to the odor used to condition the paternal generation and possessing an enhanced neuroanatomical representation for that odor. In this study, we first injected RNA extracted from sperm of male mice that underwent olfactory fear conditioning into naive single cell zygotes and found that both male and female adults that develop from these embryos have increased sensitivity and enhanced neuroanatomical representation for the odor (Odor A) with which the paternal male had been conditioned. Next, we found that female, but not male offspring sired by males conditioned with Odor A show enhanced freezing when presented with Odor A after being exposed to a sub-threshold olfactory fear conditioning protocol that consisted of only a single Odor A + shock pairing. Our data provide evidence that RNA found in the paternal germline after exposure to salient sensory experiences can contribute to intergenerational influences of such experiences, and that such intergenerational influences confer an element of adaptation to the filial generation. In so doing, our work suggests that some causes (sperm RNA) and consequences (behavioral flexibility) of intergenerational influences of parental experiences are conserved across experiences as diverse as stressors, dietary manipulations, and sensory experiences.

zoology↗

bioRxiv2018

Modulation of fear generalization by the zona incerta

Fear expressed towards threat-associated stimuli is an adaptive behavioral response. In contrast, the generalization of fear responses toward non-threatening cues is maladaptive and a debilitating dimension of trauma- and anxiety-related disorders. Expressing fear to appropriate stimuli and suppressing fear generalization requires integration of relevant sensory information and motor output. While thalamic and sub-thalamic brain regions play important roles in sensorimotor integration, very little is known about the contribution of these regions to the phenomenon of fear generalization. In this study, we sought to determine whether fear generalization could be modulated by the zona incerta (ZI), a sub-thalamic brain region that influences sensory discrimination, defensive responses, and retrieval of fear memories. To do so, we combined differential intensity-based auditory fear conditioning protocols in mice with C-FOS immunohistochemistry and DREADD-based manipulation of neuronal activity in the ZI. C-FOS immunohistochemistry revealed an inverse relationship between ZI activation and fear generalization - the ZI was less active in animals that generalized fear. In agreement with this relationship, chemogenetic inhibition of the ZI resulted in fear generalization, while chemogenetic activation of the ZI suppressed fear generalization. Furthermore, targeted stimulation of GABAergic cells in the ZI reduced fear generalization. To conclude, our data suggest that stimulation of the ZI could be used to treat fear generalization in the context of trauma- and anxiety-related disorders.

neuroscience↗