Abstracts

Rationale: Reduced excitatory input to cortical interneurons may decrease the strength of synaptic inhibition, and contribute to epileptogenesis following traumatic brain injuries. Axonal sprouting and enhanced excitatory synaptic input onto layer V pyramidal neurons is present in rodent partially isolated (“undercut”) neocortex, a model of post-traumatic epileptogenesis. We hypothesized that sprouted axons of cortical layer V pyramidal neurons also make stronger excitatory connections onto interneurons and affect network interactions. We used laser scanning photostimulation to assess the strength and distribution of excitatory and inhibitory synaptic inputs to cortical layer V fast-spiking (FS) interneurons.Methods: Coronal cortical slices were prepared from transgenic mice expressing GAD67-GFP in FS interneurons, and submerged in re-circulating ACSF containing 200 µM caged glutamate. Glutamate uncaging was accomplished by gating a pulsed 355 nm laser beam for 200-400 μs at each grid spot. Cortical layers II ~ VI were stimulated in grids of 500~550 x 800~1000 µm with 50 µm spacing. Evoked excitatory synaptic currents (EPSCs) were recorded from layer V GFP-expressing neurons that were voltage clamped at -70 mV and +20 mV. Results: In control mice, most EPSCs in FS neurons were evoked from layer V, within a radius of 200 µm of somata. The cumulative EPSC amplitudes, evoked by uncaging within 150 µm radii of somata, increased significantly in FS cells of slices from undercut cortex, indicating that these interneurons received stronger excitatory input from pyramidal neurons in layer V. The frequencies and amplitudes of spontaneous EPSCs were unaltered in FS cells, but these events were slower with longer rise times and decay time constants, suggesting increased eletrotonic filtering.Conclusions: These findings suggest that in this model of posttraumatic epilepsy, excitatory synaptic input to FS interneurons is enhanced, and may in part balance the enhanced excitatory synaptic connectivity between pyramidal neurons within the cortical network. Enhanced excitation of FS interneurons may also facilitate synchronization of cortical circuits and contribute to epileptogenesis. Supported by NIH grants NS12151 and NS 39579-06 from the NINDS.