Transient enhancement of inhibitory synaptic transmission in hippocampal CA1 pyramidal neurons after cerebral ischemia

• Published in: Neuroscience Vol. 160; no. 2; pp. 412 - 418
• Main Authors: Liang, R, Pang, Z.-P, Deng, P, Xu, Z.C
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 05.05.2009; Elsevier
• Subjects: Animals; Biological and medical sciences; Brain Ischemia - physiopathology; cell death; Evoked Potentials - physiology; excitotoxicity; Fundamental and applied biological sciences. Psychology; GABA A receptor; Hippocampus - cytology; Hippocampus - physiology; In Vitro Techniques; Inhibitory Postsynaptic Potentials - physiology; Male; Medical sciences; Miniature Postsynaptic Potentials - physiology; Neurology; Pyramidal Cells - metabolism; Pyramidal Cells - physiology; Rats; Rats, Wistar; Receptor, Adenosine A1 - physiology; Receptors, GABA-A - genetics; Receptors, GABA-A - metabolism; Reperfusion Injury - physiopathology; RNA, Messenger - analysis; Statistics, Nonparametric; stroke; Vascular diseases and vascular malformations of the nervous system; Vertebrates: nervous system and sense organs; 8-cyclopentyl-1,3-dipropylxanthine; inhibitory postsynaptic current; miniature inhibitory postsynaptic current; GABA A receptor; cell death; evoked inhibitory postsynaptic current; mIPSC; (−)-2-amino-5-phosphonopentanoic acid; PKA; 6-cyano-7-nitroquinoxaline-2,3-dione; ACSF; stroke; CNQX; D-APV; eIPSC; artificial cerebrospinal fluid; PPR; IPSC; TTX; tetrodotoxin; excitotoxicity; DPCPX; protein kinase A; paired-pulse ratio; Nervous system diseases; Stroke; Toxicity; Central nervous system; Cardiovascular disease; Cerebral disorder; Encephalon; Vascular disease; Cell death; Synaptic transmission; Excitotoxicity; Central nervous system disease; Brain ischemia; Pyramidal neuron; GABAA receptor; Gabaergic receptor A; Cerebrovascular disease; Hippocampus
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2009.02.046

Abstract Pyramidal neurons in hippocampal CA1 regions are highly sensitive to cerebral ischemia. Alterations of excitatory and inhibitory synaptic transmission may contribute to the ischemia-induced neuronal degeneration. However, little is known about the changes of GABAergic synaptic transmission in the hippocampus following reperfusion. We examined the GABAA receptor-mediated inhibitory postsynaptic currents (IPSCs) in CA1 pyramidal neurons 12 and 24 h after transient forebrain ischemia in rats. The amplitudes of evoked inhibitory postsynaptic currents (eIPSCs) were increased significantly 12 h after ischemia and returned to control levels 24 h following reperfusion. The potentiation of eIPSCs was accompanied by an increase of miniature inhibitory postsynaptic current (mIPSC) amplitude, and an enhanced response to exogenous application of GABA, indicating the involvement of postsynaptic mechanisms. Furthermore, there was no obvious change of the paired-pulse ratio (PPR) of eIPSCs and the frequency of mIPSCs, suggesting that the potentiation of eIPSCs might not be due to the increased presynaptic release. Blockade of adenosine A1 receptors led to a decrease of eIPSCs amplitude in post-ischemic neurons but not in control neurons, without affecting the frequency of mIPSCs and the PPR of eIPSCs. Thus, tonic activation of adenosine A1 receptors might, at least in part, contribute to the enhancement of inhibitory synaptic transmission in CA1 neurons after forebrain ischemia. The transient enhancement of inhibitory neurotransmission might temporarily protect CA1 pyramidal neurons, and delay the process of neuronal death after cerebral ischemia.