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 (I (h)). In addition, the maximal firing frequency upon depolarizing stimuli was decreased. The increase in I (h) amplitude was paralleled by the appearance of somatic HCN channels in immunohistochemical staining and the occurrence of somatic I (h) 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.