Biology subjects

Cain, R. E.

Publications and source records attributed to Cain, R. E..

2 recordsLinked to original sources

bioRxiv2025

Nano-organization of synapses defines synaptic release properties at cortical neuron dendritic spines

Visualization of the submicron organization of excitatory synapses has revealed an unexpectedly ordered architecture consisting of nanocolumns of synaptic proteins that group into nanomodules which scale in number as spine size increases. How these features are related to synaptic function has remained unclear. Here, using super-resolution followed by live-cell line-scan imaging, we find that the size of the smallest miniature calcium and glutamate events are the same, regardless of whether spines have one or two nanopuncta of PSD-95, and that miniature synaptic response in all spines are best fit by a three term Poisson. Two nanomodule spines exhibit more large events without a significant change in event frequency, with the number of the largest events increasing disproportionately. These data support a model where nanomodules define sites of synaptic release and where the nanoarchitecture of synaptic proteins specifies subtypes of excitatory synapses, with increasing numbers of nanomodules increasing coordinated multivesicular release.

neuroscience↗

bioRxiv2023

EphrinB2 knockdown in spinal cord astrocytes preserves diaphragm innervation in a mutant SOD1 mouse model of ALS

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by motor neuron loss. Importantly, non-neuronal cell types such as astrocytes also play significant roles in disease pathogenesis. However, mechanisms of astrocyte contribution to ALS remain incompletely understood. Astrocyte involvement suggests that transcellular signaling may play a role in disease. We examined contribution of transmembrane signaling molecule ephrinB2 to ALS pathogenesis, in particular its role in driving motor neuron damage by spinal cord astrocytes. In symptomatic SOD1G93A mice (a well-established ALS model), ephrinB2 expression was dramatically increased in ventral horn astrocytes. Reducing ephrinB2 in the cervical spinal cord ventral horn via viral-mediated shRNA delivery reduced motor neuron loss and preserved respiratory function by maintaining phrenic motor neuron innervation of diaphragm. EphrinB2 expression was also elevated in human ALS spinal cord. These findings implicate ephrinB2 upregulation as both a transcellular signaling mechanism in mutant SOD1-associated ALS and a promising therapeutic target.

neuroscience↗