[Abstract Title]. - Society for Neuroscience

Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 250.6/V18
Topic: C.06.f. Circuits and systems
Support: NIH Grant R37 NS-32403
Title: Epilepsy-associated dysregulation of recurrent feedback inhibition in hippocampal area
ca1
Authors: C. YUE, C.-W. ANG, *F. WEISSINGER, D. COULTER;
Children's Hosp. Philadelphia, Philadelphia, PA
Abstract: Temporal lobe epilepsy (TLE) is the most prevalent seizure disorder in adults. It is an
acquired disorder, defined by seizures involving limbic structures, including the hippocampus.
Most studies examining mechanisms of TLE have focused on changes in the synaptic and
intrinsic properties of hippocampal neurons. However, it is not clear how reorganization in the
local circuitry affects integration of cortical inputs into the hippocampus. In the normal rodent,
direct cortical input into the hippocampus, the temporoammonic (TA) pathway, is highly
segregated to the distal apical tuft of CA1 pyramidal neurons by feedforward inhibition mediated
by stratum lacunosum moleculare intereneuons, and TA interaction with Schaffer collateral
EPSPs is regulated by feedback inhibition, mediated by a population of stratum oriens
interneurons. Previous studies showed that, in pilocarpine-treated rats exhibiting spontaneous
seizures, the disruption of feedforward inhibitory control of the TA pathway results in a loss of
spatial segregation of TA EPSPs to CA1 stratum lacunosum moleculare, with propagation of the
TA EPSPs to stratum radiatum and stratum pyramidale. To examine how alterations in feedback
inhibitory regulation may further dysregulate TA inputs after pilocarpine-induced SE, we used
voltage sensitive dye imaging combined with dendritic whole cell recording. To compare the
spatiotemporal patterns of feedback inhibition mediated by oriens/alveus interneurons in control
and chronic epileptic animals, we stimulated CA1 pyramidal cell axons antidromically by
activating the alveus, using varying stimulation frequencies. We found that, in slices from
epileptic rats, there was a significant lack of oriens/alveus mediated inhibition in response to
alvear stimulation, both in proximal and distal dendritic areas. This deficit in oriens/alveus
mediated recurrent inhibition results in an inability of CA1 circuitry to restrict and/or gate TA
inputs impinging onto CA1 distal dendrites, allowing propagation of TA EPSPs to the CA1
soma. These changes in the local circuitry contribute further to persistent hyperexcitability in the
hippocampal area CA1 that may underlie the generation of paroxysmal activity in the
hippocampus.
Disclosures: C. Yue, None; F. Weissinger, None; C. Ang, None; D. Coulter, None.
Poster