Homeostatic increase in excitability in area CA1 after Schaffer collateral transection in vivo

Epilepsy is a significant long-term consequence of traumatic brain injury (TBI) and is likely to result from multiple mechanisms. One feature that is common to many forms of TBI is denervation. We asked whether chronic partial denervation in vivo would lead to a homeostatic increase in the excitability of a denervated cell population.

To answer this question, we took advantage of the unique anatomy of the hippocampus where the input to the CA1 neurons, the Schaffer collaterals, could be transected in vivo with preservation of their outputs and only minor cell death.

We observed a delayed increase in neuronal excitability, as apparent in extracellular recordings from hippocampal brain slices prepared 14 days (but not 3 days) post lesion. Although population spikes in slices from control and lesioned animals were comparable under resting conditions, application of solutions that were mildly proconvulsive (high K(+) , low Mg(2+) , low concentrations of bicuculline) produced increases in the number of population spikes in slices from lesioned rats, but not in slices from unlesioned sham controls. Denervation did not produce changes in several markers of γ-aminobutyric acid (GABA)ergic synaptic inhibition, including the number of GABAergic neurons, α1 GABA(A) receptor subunits, the vesicular GABA transporter, or miniature inhibitory postsynaptic currents.

We conclude that chronic partial denervation does lead to a delayed homeostatic increase in neuronal excitability, and may, therefore, contribute to the long-term neurologic consequences of TBI.