title: Shift from phasic to tonic GABAergic transmission following laser-lesions in the rat visual cortex.
abstract: Reduction in the strength of GABAergic neurotransmission has often been reported following brain lesions. This weakened inhibition is believed to influence neurological deficits, neuronal hyperexcitability and functional recovery after brain injuries. Uncovering the mechanisms underlying the altered inhibition is therefore crucial. In the present study we used an ex vivo-in vitro model of laser lesions in the rat visual cortex to characterize the cellular correlates of changes in GABAergic transmission in the tissue adjacent to the injury. In the first week post-injury the number of VGAT positive GABAergic terminals as well as the expression level of the GABA synthesizing enzymes GAD67 and GAD65 remained unaltered. However, a reduced frequency of miniature inhibitory postsynaptic currents (mIPSCs) together with an increased paired-pulse ratio (PPR) of evoked IPSCs suggested a functional reduction of phasic GABA release. In parallel, we found an enhancement in the GABAA receptor-mediated tonic inhibition. On the basis of these findings, we propose that cortical lesions provoke a shift in GABAergic transmission, decreasing the phasic and reinforcing the tonic component. We therefore suggest that it is not, as traditionally assumed, the overall inhibitory strength to be primarily compromised by a cortical lesion but rather the temporal accuracy of the GABAergic synaptic signaling.
authors.affiliation: Institute of Physiology and Pathophysiology, University Medical Center of the Johannes-Gutenberg University Mainz, Duesbergweg 6, 55128, Mainz, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Imbrosci
authors.forename: Ute
authors.initials: U
authors.lastname: Neubacher
authors.forename: Robin
authors.initials: R
authors.lastname: White
authors.forename: Ulf T
authors.initials: UT
authors.lastname: Eysel
authors.forename: Thomas
authors.initials: T
authors.lastname: Mittmann
mesh_terms: D000818:Animals; D059330:GABAergic Neurons / Q000378:metabolism / Q000502:physiology*; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000378:metabolism; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials; D007834:Lasers / Q000009:adverse effects; D055369:Miniature Postsynaptic Potentials; D051381:Rats; D020318:Rats, Long-Evans; D013569:Synapses / Q000378:metabolism / Q000502:physiology; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000235:genetics / Q000378:metabolism; D014793:Visual Cortex / Q000293:injuries / Q000473:pathology / Q000503:physiopathology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: C118623:Slc32a1 protein, rat; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; C401141:glutamate decarboxylase 2