Activity-dependent determinants of neuronal vulnerability in Traumatic Brain Injury

Orateur : Francesco ROSELLI (Universität Ulm, Allemagne)

Excessive excitation has been hypothesized to subsume a significant part of the acute damage oc-curring after Traumatic Brain Injury (TBI). However, reduced neuronal excitability, loss of neuronal firing and a disturbed excitation/inhibition balance have been detected. Parvalbumin (PV) interneu-rons are major regulators of perisomatic inhibition, principal neurons firing and overall cortical ex-citability. However, their role in acute TBI pathogenic cascades is unclear. We exploited the che-mogenetic PSAM/PSEM control of PV-Cre+ neurons and the DREADDs control of principal neu-rons in a blunt model of TBI to explore the role of inhibition in shaping neuronal vulnerability to TBI. We demonstrated that inactivation of PV interneurons at the instance or soon after trauma en-hances survival of principal neurons and reduces gliosis at 7dpi whereas, activation of PV interneu-rons decreased neuronal survival. The protective effect of PV inactivation was suppressed by ex-pressing the nuclear calcium buffer PV-NLS in principal neurons, implying an activity-dependent neuroprotective signal. In fact, protective effects were obtained by increasing the excitability of principal neurons directly using DREADDs. Thus, we show that sustaining neuronal excitation in the early phases of TBI may reduce neuronal vulnerability by increasing activity-dependent survival, while excess activation of perisomatic inhibition is detrimental to neuronal integrity.

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