title: Enhancement of inhibitory synaptic transmission in large aspiny neurons after transient cerebral ischemia.
abstract: Large aspiny neurons and most of the GABAergic interneurons survive transient cerebral ischemia while medium spiny neurons degenerate in 24 h. Expression of a long-term enhancement of excitatory transmission in medium spiny neurons but not in large aspiny neurons has been indicated to contribute to this selective vulnerability. Because neuronal excitability is determined by the counterbalance of excitation and inhibition, the present study examined inhibitory synaptic transmission in large aspiny neurons after ischemia in rats. Transient cerebral ischemia was induced for 22 min using the four-vessel occlusion method and whole-cell voltage-clamp recording was performed on striatal slices. The amplitudes of evoked inhibitory postsynaptic currents in large aspiny neurons were significantly increased at 3 and 24 h after ischemia, which was mediated by the increase of presynaptic release. Postsynaptic responses were depressed at 24 h after ischemia. Inhibitory postsynaptic currents could be evoked in large aspiny neurons at 24 h after ischemia, suggesting that they receive GABAergic inputs from the survived GABAergic interneurons. Muscimol, a GABA(A) receptor agonist, presynaptically facilitated inhibitory synaptic transmission at 24 h after ischemia. Such facilitation was dependent on the extracellular calcium and voltage-gated sodium channels. The present study demonstrates an enhancement of inhibitory synaptic transmission in large aspiny neurons after ischemia, which might reduce excitotoxicity and contribute, at least in part, to the survival of large aspiny neurons. Our data also suggest that large aspiny neurons might receive inhibitory inputs from GABAergic interneurons.
authors.affiliation: Department of Anatomy and Cell Biology, Indiana University School of Medicine, 635 Barnhill Drive, MS 507, Indianapolis, IN 46202, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: Z
authors.initials: Z
authors.lastname: Lei
authors.forename: Z C
authors.initials: ZC
authors.lastname: Xu
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D001640:Bicuculline / Q000031:analogs & derivatives / Q000494:pharmacology; D001703:Biophysics; D001710:Biotin / Q000031:analogs & derivatives / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003342:Corpus Striatum / Q000473:pathology; D004195:Disease Models, Animal; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D005968:Glutamate Decarboxylase / Q000378:metabolism; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D002546:Ischemic Attack, Transient / Q000473:pathology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009118:Muscimol / Q000494:pharmacology; D009474:Neurons / Q000145:classification / Q000502:physiology*; D034445:Ovulation Inhibition / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D026941:Sodium Channel Blockers / Q000494:pharmacology; D009435:Synaptic Transmission / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000494:pharmacology
chemical_list: D018691:Excitatory Amino Acid Antagonists; D018755:GABA Agonists; D018756:GABA Antagonists; D026941:Sodium Channel Blockers; C070614:neurobiotin; D009118:Muscimol; C017069:bicuculline methiodide; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D001710:Biotin; D015763:2-Amino-5-phosphonovalerate; D002795:Choline O-Acetyltransferase; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; D002118:Calcium; D001640:Bicuculline