Biology subjects

Anacker, C.

Publications and source records attributed to Anacker, C..

3 recordsLinked to original sources

bioRxiv2025

Maturation of Hippocampus-Medial Prefrontal Cortex Projections Defines a Pathway-Specific Sensitive Period for Cognitive Flexibility

The septotemporal axis of the hippocampus separates it into domains with unique molecular, cellular, downstream connectivity and behavioral profiles, and yet very little is known about the ontogenesis of these highly specialized subcircuits. Here, we used viral tracing, optogenetic-assisted patch clamping, chemogenetics and behavior in mice to examine changes in domain-defined hippocampus efferent projections from postnatal day (P)10 to P60. We found distinct anatomical and synaptic developmental signatures in ventral and intermediate CA1 downstream connectivity, with unique contributions to the prelimbic and infralimbic subregions of the medial prefrontal cortex (mPFC). Juvenile inhibition of the ventral and intermediate CA1-mPFC pathways led to opposing modulation of adult cognitive flexibility, establishing a sex- and pathway-specific sensitive period preceding the stabilization of CA1-mPFC synaptic transmission. Our data elucidate domain- and target-defined postnatal maturation of hippocampus efferents, identifying juvenility as a CA1-mPFC sensitive period with crucial implications for early life influences on adult cognition.

neuroscience↗

bioRxiv2024

Resilience to Early Life Adversity Effects on Stress Reactivity by Postnatal Knockdown of 5-HT1A Autoreceptors

Early Life Adversity (ELA) predisposes to stress hypersensitivity in adulthood, but neurobiological mechanisms that protect from the enduring effects of ELA are poorly understood. Serotonin 1A (5HT1A) autoreceptors in the raphe nuclei regulate adult stress vulnerability, but whether 5HT1A could be targeted to prevent ELA effects on susceptibility to future stressors is unknown. Here, we exposed mice with postnatal knockdown of 5HT1A autoreceptors to the limited bedding and nesting model of ELA from postnatal day (P)3-10 and tested behavioral, neuroendocrine, neurogenic, and neuroinflammatory responses to an acute swim stress in male and female mice in adolescence (P35) and in adulthood (P56). In females, ELA decreased raphe 5HT neuron activity in adulthood and increased passive coping with the acute swim stress, corticosterone levels, neuronal activity, and corticotropin-releasing factor (CRF) levels in the paraventricular nucleus (PVN) of the hypothalamus. ELA also reduced neurogenesis in the ventral dentate gyrus (vDG) of the hippocampus, an important mediator of individual differences in stress susceptibility, and increased microglia activation in the PVN and vDG. These effects of ELA were specific to females and manifested predominantly in adulthood, but not earlier on in adolescence. Postnatal knockdown of 5HT1A autoreceptors prevented these effects of ELA on 5HT neuron activity, stress reactivity, neurogenesis, and neuroinflammation in adult female mice. Our findings demonstrate that ELA induces long-lasting and sex-specific impairments in the serotonin system, stress reactivity, and vDG function, and identify 5HT1A autoreceptors as potential targets to prevent these enduring effects of ELA.

neuroscience↗

bioRxiv2021

Mouse brain-wide mitochondrial connectivity anchored in gene, brain and behavior

The brain and behavior are under energetic constraints, limited by mitochondrial energy transformation capacity. However, the mitochondria-behavior relationship has not been systematically studied on a brain-wide scale. Here we examined the association between multiple features of mitochondrial respiratory chain capacity and stress-related behaviors in mice with diverse behavioral phenotypes. Miniaturized assays of mitochondrial respiratory chain enzyme activities and mitochondrial DNA (mtDNA) content were deployed on 571 samples across 17 brain areas, defining specific patterns of mito-behavior associations. By applying multi-slice network analysis to our brain-wide mitochondrial dataset, we identified three large-scale networks of brain areas with shared mitochondrial signatures. A major network composed of cortico-striatal areas exhibited the strongest mitochondria-behavior correlations, accounting for up to 50% of animal-to-animal behavioral differences, suggesting that this mito-based network is functionally significant. The mito-based brain networks also overlapped with regional gene expression and structural connectivity and quantitatively diverged in their molecular mitochondrial phenotype signatures. Therefore, this work provides convergent multimodal evidence anchored in enzyme activities, gene expression, and animal behavior that distinct, behaviorally-relevant mitochondrial phenotypes exist across the mouse brain.

neuroscience↗