Abstract TP105: Increaed GABAA Mediated Synaptic Activity and Structural Remodeling in Peri-infarct Cortex Layer 5 in the Post-stroke Rodent Brain.

Introduction: The mechanisms of functional recovery after stroke are thought to be based on structural and functional changes in brain circuits adjacent to or connected with the stroke site. Deciphering these changes at the synaptic level is key to understanding the re-organization of the synaptic circuitry. Here we use a combined approach of i) array tomography to determine the composition of GABA synapses in the post-stroke mouse brain, with ii) electrophysiology to determine whether stroke leads to functional changes in GABA A receptor-mediated neurotransmission. Methods: A cortical lesion was induced in 12-week-old C57BL/6J male mice using the distal middle cerebral artery occlusion model of ischemia. For array tomography, small tissue was removed from the peri-infarct cortex and ribbons of serial ultrathin sections were obtained. Ribbons were stained with antibodies for synaptic markers. Analysis of the resultant staining pattern was used to quantify GABAergic synapses. In addition, whole-cell patch clamp recordings from acute neocortical brain slices were performed to evaluate GABA-mediated synaptic signaling in the peri-infarct cortex. Behavior was evaluated weekly. Results: At 1 week post-stroke, the array tomography data revealed an increase in the density and proportion of alpha1 subunit-containing GABAergic synapses in layer 5 of the peri-infarct cortex (Density: 0.064 vs 0.036 synapses/μm3. Proportion: 15.3 vs 9.1 %, p A receptor-mediated currents were enhanced in layer 5, but not in layer 2/3. These changes were specific to the pyramidal neurons. Behavioral impairment after stroke was observed only at 1 week compared to sham mice (p Conclusion: Our results suggest that stroke leads to an increased expression of functional GABA A receptors in peri-infarct neocortex and that these changes are layer- and cell type-specific. These synaptic changes may represent a mechanism of post-stroke functional recovery and remapping of surviving circuits.