title: Synaptic reorganization of inhibitory hilar interneuron circuitry after traumatic brain injury in mice.
abstract: Functional plasticity of synaptic networks in the dentate gyrus has been implicated in the development of posttraumatic epilepsy and in cognitive dysfunction after traumatic brain injury, but little is known about potentially pathogenic changes in inhibitory circuits. We examined synaptic inhibition of dentate granule cells and excitability of surviving GABAergic hilar interneurons 8-13 weeks after cortical contusion brain injury in transgenic mice that express enhanced green fluorescent protein in a subpopulation of inhibitory neurons. Whole-cell voltage-clamp recordings in granule cells revealed a reduction in spontaneous and miniature IPSC frequency after head injury; no concurrent change in paired-pulse ratio was found in granule cells after paired electrical stimulation of the hilus. Despite reduced inhibitory input to granule cells, action potential and EPSC frequencies were increased in hilar GABA neurons from slices ipsilateral to the injury versus those from control or contralateral slices. Furthermore, increased excitatory synaptic activity was detected in hilar GABA neurons ipsilateral to the injury after glutamate photostimulation of either the granule cell or CA3 pyramidal cell layers. Together, these findings suggest that excitatory drive to surviving hilar GABA neurons is enhanced by convergent input from both pyramidal and granule cells, but synaptic inhibition of granule cells is not fully restored after injury. This rewiring of circuitry regulating hilar inhibitory neurons may reflect an important compensatory mechanism, but it may also contribute to network destabilization by increasing the relative impact of surviving individual interneurons in controlling granule cell excitability in the posttraumatic dentate gyrus.
authors.affiliation: Department of Physiology, University of Kentucky, Lexington, Kentucky 40536-0298, USA.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Hunt
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Scheff
authors.forename: Bret N
authors.initials: BN
authors.lastname: Smith
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000503:physiopathology*; D018891:Dentate Gyrus / Q000503:physiopathology*; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005260:Female; D053444:Inhibitory Postsynaptic Potentials / Q000502:physiology; D007395:Interneurons / Q000502:physiology*; D008297:Male; D051379:Mice; D055369:Miniature Postsynaptic Potentials / Q000502:physiology; D009415:Nerve Net / Q000503:physiopathology*; D018709:Statistics, Nonparametric; D013569:Synapses / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D005680:gamma-Aminobutyric Acid