Biology subjects

Natale, S.

Publications and source records attributed to Natale, S..

3 recordsLinked to original sources

bioRxiv2025

Immediate early genes act in the medial hypothalamus to promote adaptation to social defeat

Territorial animals must moderate their social aggression and avoidance behaviors in a manner that maximizes their access to resources and fitness. The ventrolateral division of the ventromedial hypothalamic nucleus (VMHvl) has been shown to control both social aggression and avoidance in mice, and emerging data show that neural plasticity within VMHvl can drive the experience-dependent adaptation of these behaviors. Here, we investigated the contribution of immediate early gene (IEG) function in supporting this plasticity. In initial experiments, we found that downregulation of the IEG cFos in VMHvl did not significantly moderate the long-term increase in social avoidance seen following an experience of social defeat. However, local knockout of the IEG master regulator Serum Response Factor (SRF, Srf) was able to blunt the impact of social defeat on social avoidance and prevented the effect of social defeat on local optogenetic-evoked social avoidance behavior, demonstrating a critical role for subcortical IEG activity in social defeat-induced behavioral plasticity. To test whether NMDA receptor dependent plasticity might be involved in this effect, we locally infused the NMDA receptor antagonist MK-801 into VMHvl and assessed the impact of social defeat. Unexpectedly, MK-801 treatment led to an increase in social defeat-induced avoidance, pointing to the existence of opposing IEG and NMDA receptor-dependent adaptive mechanisms in medial hypothalamus. These findings suggest that multiple neural plasticity mechanisms are likely to be at play in the hypothalamic nuclei supporting innate behavior adaptation and show how IEG blockade can be used as a genetic tool to systematically map neural plasticity in the brain. Significance StatementThe role of IEGs in experience-dependent plasticity has not been investigated in subcortical structures until now. Our findings suggest IEGs expression is essential for adaptive behavioral changes in the VMHvl following social defeat and can potentially be used to map behavioral adaptation across brain regions. Our study also indicates a potential use of IEGs as targets of gene therapy for mitigating maladaptive behavioral adaptations.

neuroscience↗

bioRxiv2021

Microglia complement signaling promotes neuronal elimination and normal brain functional connectivity

Complement signaling is thought to serve as an opsonization signal to promote the phagocytosis of synapses by microglia. However, while its role in synaptic remodeling has been demonstrated in the retino-thalamic system, it remains unclear whether complement signaling mediates synaptic pruning in the brain more generally. Here we show that mice lacking the complement 3 receptor (C3r), the major microglia complement receptor, fail to show a deficit in either synaptic pruning or axon elimination in the developing mouse cortex. Instead, mice lacking C3r show a deficit in the perinatal elimination of neurons, both in the retina as well as in the cortex, a deficit that is associated with increased cortical thickness and enhanced functional connectivity in these regions in adulthood. These data demonstrate a preferential role for complement in promoting neuronal elimination in the developing brain and argue for a reconsideration of the role of complement in synaptic pruning.

neuroscience↗

bioRxiv2020

A role for cerebral cortex in the suppression of innate defensive behavior

The cerebral cortex is involved in the control of cognition and the processing of learned information and it appears to have a role in the adaptation of behavior in response to unpredictable circumstances. In addition, the cortex may have a role in the regulation of innate responses since rodents, cats or primates with surgical removal or accidental destruction of cortical regions show excessive irritability, aggression and rage elicited by threatening stimuli. However, it remains unclear whether cortex has an acute role in suppressing innate threat responses because the imprecision and chronic nature of these lesions leaves open the possibility that compensatory processes may underlie some of these phenotypes. In the present study we used pharmacogenetic inhibition to precisely, rapidly and reversibly suppress cortical pyramidal neuron function and examine its contribution to defensive behaviors elicited by a variety of innately aversive stimuli. Inhibition of cortex caused an increase of defensive responses elicited by an aggressive conspecific, a novel prey, and a physically stressful stimulus. These findings are consistent with a role of cortex in the acute inhibition of innate defensive behaviors.

neuroscience↗