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McNabb, M. C.

Publications and source records attributed to McNabb, M. C..

2 recordsLinked to original sources

Astrocyte coverage of excitatory synapses correlates to measures of synapse structure and function in primary visual cortex

Most excitatory synapses in the mammalian brain are contacted by astrocytes, forming the tripartite synapse. This interface is thought to be critical for glutamate turnover and structural or functional dynamics of synapses. While the degree of synaptic contact of astrocytes is known to vary across brain regions and animal species, the implications of this variability remain unknown. Furthermore, precisely how astrocyte coverage of synapses relates to in vivo functional properties of individual dendritic spines has yet to be investigated. Here, we characterized perisynaptic astrocyte processes (PAPs) contacting synapses of pyramidal neurons of the ferret visual cortex and, using correlative light and electron microscopy, examined their relationship to synaptic strength and to sensory-evoked Ca2+ activity. Nearly all synapses were contacted by PAPs, and most were contacted along the axon-spine interface (ASI). Structurally, we found that the degree of PAP coverage scaled with synapse size and complexity. Functionally, we found that PAP coverage scaled with the selectivity of Ca2+ responses of individual synapses to visual stimuli and, at least for the largest synapses, scaled with the reliability of visual stimuli to evoke postsynaptic Ca2+ events. Our study shows astrocyte coverage is highly correlated with structural properties of excitatory synapses in the visual cortex and implicates astrocytes as a contributor to reliable sensory activation.

neuroscience↗

A multi-faceted analysis of synapses reveals the role of neuroligin-1 cleavage in presynaptic vesicle accumulation in the lateral amygdala

Neuroligin-1 (NLGN1) is a cell adhesion molecule found at excitatory glutamatergic synapses in the brain which regulates synaptic function and maturation. Extracellular cleavage of NLGN1 by proteases has been shown to control vesicle release in cultured neurons, but nothing is known about the underlying changes to synapse structure that accompany this, or how synapse function is affected in brain tissue. We found that prevention of NLGN1 cleavage through mutation to the extracellular stalk domain increases synaptic vesicle docking and miniature excitatory post-synaptic current frequency at synapses of the lateral amygdala. Using a novel volume electron microscopy (vEM) analysis pipeline based on deep learning extraction of thousands of synapses and vesicles clouds and subsequent spatial analyses, we found that the total pool of synaptic vesicles shifts closer to the synapse in mutants. Furthermore, we observed an increased frequency of incomplete synapses that lack vesicle accumulation, pointing towards disruption of synaptic pruning and accumulation of putatively non-functioning synapses. Our study provides evidence of a structural and functional role of NLGN1 cleavage in native brain tissue, and establishes a foundation for vEM analysis of synapse-vesicle spatial relationships in other animal models of dysfunction and disease.

neuroscience↗