Natale, S. | bioRxiv Science

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↗