O'Connell, C. | Search bioRxiv

bioRxiv2024

Synaptic Proteomes of Cortical Interneuron Classes Revealed by Antibody Directed Proximity Labeling.

Subtypes of inhibitory interneurons play diverse roles within neural circuits in cerebral cortex. Defining the molecular underpinnings of interneuron functions within cortical circuits will require identification of interneuron synaptic proteomes. In this study, we first combined genetically directed expression of tdTomato-synaptophysin with antibody-directed proximity labeling and tandem mass spectrometry to identify synaptic proteomes of three major interneuron classes in mouse cortex: parvalbumin (PV), somatostatin (SS), and vasoactive intestinal peptide (VIP). After stringent filtering we identified 581 proteins: 228 identified in all cell classes and 353 in one or two of three classes. The PV class had the largest number of uniquely identified proteins (141), followed by VIP (30) and SST (20). Consistent with previously reported electrophysiological evidence, PV presynaptic proteomes were enriched for NMDA receptor subunits and scaffolding proteins. We used antibodies against synaptotagmin 2 (Syt2), a presynaptic protein present at PV synapses, to confirm NMDAR localization, and to find that the mu-opioid receptor agonist buprenorphine rapidly caused reorganization of the PV presynaptic proteome. Overall, our results reveal proteomes of PV, SST, and VIP interneurons in cortex that likely underlie distinct and dynamic interneuron synaptic properties.

neuroscience↗

bioRxiv2023

Model matters: Differential outcomes in traumatic optic neuropathy pathophysiology between blunt and blast-wave mediated head injuries.

Over 3 million people in the United States live with long-term disability as a result of a traumatic brain injury (TBI). The purpose of this study was to characterize and compare two different animal models of TBI (blunt head trauma and blast TBI) to determine common and divergent characteristics of these models. With recent literature reviews noting the prevalence of visual system injury in animal models of TBI, coupled with clinical estimates of 50-75% of all TBI cases, we decided to assess commonalities, if they existed, through visual system injury. Blast, repeat blast, and blunt injury were induced in adult male mice to observe and quantify visual deficits. Retinal ganglion cell loss and axonal degeneration in the optic tract, superior colliculus, and lateral geniculate nuclei were examined to trace injury outcomes throughout major vision-associated areas. Optokinetic response, immunohistochemistry, and western blots were analyzed. Where a single blunt injury produces significant visual deficits a single blast injury appears to have less severe visual consequences. Visual deficits after repeat blasts are similar to a single blast. Single blast injury induces contralateral damage to right optic chiasm and tract whereas bilateral injury follows a single blunt injury. Repeat blast injuries are required to see degeneration patterns in downstream regions similar to the damage seen in a single blunt injury. This finding is further supported by Amyloid Precursor Protein (APP) staining in injured cohorts. Blunt injured groups present with staining 1.2 mm of the optic nerve, indicating axonal breakage closer to the optic chiasm. In blast groups, APP was identifiable in a bilateral pattern only in the geniculate nucleus. Evidence for unilateral neuronal degeneration in brain tissue with bilateral axonal ruptures are pivotal discoveries in this model differentiation. Analysis of the two injury models suggest there is a significant difference in the histological outcomes dependent on injury type, though visual system injury is likely present in more cases than are currently diagnosed clinically.

neuroscience↗