Traumatic Brain Injury Diminishes Feedforward Activation of Parvalbumin-Expressing Interneurons in the Dentate Gyrus
Kaitlin A. Folweiler, Guoxiang Xiong, Kaitlin M. Best, Hannah Metheny, Gabriel D. Nah, Akiva S. Cohen
Abstract
Abstract Traumatic brain injury (TBI) is associated with aberrant network hyperexcitability in the dentate gyrus (DG). GABA A ergic parvalbumin-expressing interneurons (PV-INs) in the DG regulate network excitability with strong, perisomatic inhibition, although the posttraumatic effects on PV-IN function after TBI are not well understood. In this study, we investigated physiological alterations in PV-INs one week after mild lateral fluid percussion injury (LFPI) in mice. PV-IN cell loss was observed in the dentate hilus after LFPI, with surviving PV-INs showing no change in intrinsic membrane properties. Whole-cell voltage clamp recordings in PV-INs revealed alterations in both EPSCs and IPSCs (EPSCs/IPSCs). Evoked EPSCs (eEPSCs) in PV-INs from perforant path electrical stimulation were diminished after injury but could be recovered with application of a GABA A -receptor antagonist. Furthermore, current-clamp recordings using minimal perforant path stimulation demonstrated a decrease in evoked PV-IN action potentials (APs) after LFPI, which could be restored by blocking GABA A ergic inhibition. Together, these findings suggest that injury alters synaptic input onto PV-INs, resulting in a net inhibitory effect that reduces feedforward PV-IN activation in the DG. Decreased PV-IN activation suggests a potential mechanism of DG network hyperexcitability contributing to hippocampal dysfunction after TBI.