Michaelson, S. D. | bioRxiv Science

bioRxiv2020

Syngap1 Dynamically Regulates the Fine-Scale Reorganization of Cortical Circuits in Response to Sensory Experience

Experience induces complex, neuron-specific changes in population activity within sensory cortex circuits. However, the mechanisms that enable neuron-specific changes within cortical populations remain unclear. To explore the idea that synapse strengthening is involved, we studied fine-scale cortical plasticity in Syngap1 mice, a neurodevelopmental disorder model useful for linking synapse biology to circuit functions. Repeated functional imaging of the same L2/3 somatosensory cortex neurons during single whisker experience revealed that Syngap1 selectively regulated the plasticity of a low-active, or "silent", neuronal subpopulation. Syngap1 also regulated spike-timing-dependent synaptic potentiation and experience-mediated in vivo synapse bouton formation, but not synaptic depression or bouton elimination in L2/3. Adult re-expression of Syngap1 restored plasticity of "silent" neurons, demonstrating that this gene controls dynamic cellular processes required for population-specific changes to cortical circuits during experience. These findings suggest that abnormal experience-dependent redistribution of cortical population activity may contribute to the etiology of neurodevelopmental disorders.

neuroscience↗

bioRxiv2019

Reversible Reorganization Of Basolateral Amygdala Dendrites in Male Rats Accompanies Stress Resilience

Endogenous neuropeptide Y (NPY) and corticotrophin-releasing factor (CRF) modulate the responses of the Basolateral amygdala (BLA) to stress, and are associated respectively with the development of stress resilience and vulnerability. We characterized the persistent effects of repeated NPY and CRF treatment on the structure and function of BLA principal neurons (PN) in a novel organotypic slice culture (OTC) model of rat BLA, and examined the contributions of specific NPY receptor subtypes to these neural and behavioral effects. In BLA principal neurons within the OTCs, repeated NPY treatment caused persistent attenuation of excitatory input and induced dendritic hypotrophy via Y5 receptors; conversely, CRF increased excitatory input and induced hypertrophy of BLA PNs. Repeated treatment of OTCs with NPY followed by an identical treatment with CRF, or vice versa inhibited or reversed all structural changes in OTCs. These structural responses to NPY or CRF required calcineurin or CaMKII, respectively. Finally, repeated intra-BLA injections of NPY or a Y5 receptor agonist increased social interaction and recapitulated structural changes in BLA neurons seen in OTCs, while a Y5 receptor antagonist prevented NPYs effects both on behavior and on structure. These results implicate the Y5 receptor in the long-term, anxiolytic-like effects of NPY in the BLA, consistent with an intrinsic role in stress buffering, and highlight a remarkable mechanism by which BLA neurons may adapt to different levels of stress. Moreover, BLA OTCs offer a robust model to study mechanisms associated with resilience and vulnerability to stress in BLA.\n\nSignificance StatementWithin the basolateral amygdala (BLA), Neuropeptide Y (NPY) is associated with buffering the neural stress response induced by CRF, and promoting stress resilience. We used a novel organotypic slice culture (OTC) model of BLA, complemented with in vivo studies, to examine the cellular mechanisms associated with the actions of NPY. In OTCs, repeated NPY treatment reduces the complexity of the dendritic extent of anxiogenic BLA principal neurons, making them less excitable. NPY, via activation of Y5 receptors, additionally inhibits and reverses the increases in dendritic extent and excitability induced by the stress hormone, corticotropin releasing factor (CRF). This NPY-mediated neuroplasticity indicates that resilience or vulnerability to stress may thus involve neuropeptide-mediated dendritic remodeling in BLA PNs.

neuroscience↗