Functional Alterations in Parvalbumin-Positive Interneurons after Traumatic Brain Injury in Somatosensory Cortex of Mice.

Traumatic brain injury (TBI) can lead to long-lasting cognitive deficits in the human brain, with a considerable contribution of secondary morphological and functional sequela in cortical regions distant to the lesion site. In order to uncover the role of early functional alterations in parvalbumin-positive basket cells (PV-BCs), an interneuron population required to maintain inhibition of neocortical circuits, to this dysfunctional plasticity, we investigated anatomical and electrophysiological properties of PV-BCs in PV-IRES-Cre-tdTomato mice of both sexes 24 h after a cortical impact. These experiments revealed that the number of PV-BCs was moderately decreased around the cortical impact site, while their morphology was unaffected. Patch-clamp experiments demonstrated that TBI increased the input resistance of PV-BCs and the amplitude of hyperpolarization-activated inward currents ( ). In addition, the maximal firing frequency upon depolarizing stimuli was decreased. The increase in amplitude was paralleled by the appearance of somatic HCN channels in immunohistochemical staining and the occurrence of somatic in nucleated patch recordings, suggesting that TBI induced a redistribution of HCN channels from a purely axonal to an additional somatodendritic expression. Pharmacological experiments showed that inhibition of axonal HCN-mediated currents impairs the maximal firing frequency of PV-BCs. Additional in silico simulations disclosed the general importance of axonal HCN channels to maintain high-frequency firing of PV-BCs by counteracting Na-K-pump associated hyperpolarizing currents. In summary, our results suggest that the early loss of PV-BCs and the TBI-induced distinct alterations in their electrophysiological properties can contribute to the establishment of disturbed network activity following TBI.