T Shew

University of British Columbia - Vancouver, Vancouver, British Columbia, Canada

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Publications (3)14.93 Total impact

  • T Shew, S Yip, B R Sastry
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    ABSTRACT: In the present study, possible mechanisms involved in the tetanus-induced potentiation of gamma-aminobutyric acid-A (GABA-A) receptor-mediated inhibitory postsynaptic currents (IPSCs) were investigated using the whole cell voltage-clamp technique on CA1 neurons in rat hippocampal slices. Stimulations (100 Hz) of the stratum radiatum, while voltage-clamping the membrane potential of neurons, induces a long-term potentiation (LTP) of evoked fast IPSCs while increasing the number but not the amplitude of spontaneous IPSCs (sIPSCs). The potentiation of fast IPSCs was input specific. During the period of IPSC potentiation, postsynaptic responses produced by 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol hydrochloride and baclofen, GABA-A and GABA-B agonists respectively, were not significantly different from control. CGP 36742, a GABA-B antagonist, blocked the induction of tetanus-induced potentiation of evoked and spontaneous IPSCs, while GTPgammaS, an activator of G proteins, substitution for GTP in the postsynaptic recording electrode did not occlude potentiation. Since GABA-B receptors work through G proteins, our results suggest that pre- but not postsynaptic GABA-B receptors are involved in the potentiation of fast IPSCs. A tetanus delivered when GABA-A responses were completely blocked by bicuculline suggests that GABA-A receptor activation during tetanus is not essential for the induction of potentiation. Rp-cAMPs, an antagonist of protein kinase A (PKA) activation, blocks the induction of potentiation of fast IPSCs. Forskolin, an activator of PKA, increases baseline evoked IPSCs as well as the number of sIPSCs, and a tetanic stimulation during this enhancement uncovers a long-term depression of the evoked IPSC. Sulfhydryl alkylating agents, N-ethylmaleimide and p-chloromercuribenzoic acid, which have been found to presynaptically increase GABA release and have been suggested to have effects on proteins involved in transmitter release processes occurring in nerve terminals, occlude tetanus-induced potentiation of evoked and spontaneous IPSCs. Taken together our results suggest that LTP of IPSCs originates from a presynaptic site and that GABA-B receptor activation, cyclic AMP/PKA activation and sulfhydryl-alkylation are involved. Plasticity of IPSCs as observed in this study would have significant implications for network behavior in the hippocampus.
    Journal of Neurophysiology 07/2000; 83(6):3388-401. · 3.30 Impact Factor
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    ABSTRACT: gamma-Aminobutyric acid (GABA) is the inhibitory transmitter released at Purkinje cell axon terminals in deep cerebellar nuclei (DCN). Neurons in DCN also receive excitatory glutamatergic inputs from the inferior olive. The output of DCN neurons, which depends on the balance between excitation and inhibition on these cells, is involved in cerebellar control of motor coordination. Plasticity of synaptic transmission observed in other areas of the mammalian central nervous system (CNS) has received wide attention. If GABA-ergic and/or glutamatergic synapses in DCN also undergo plasticity, it would have major implications for cerebellar function. In this review, literature evidence for GABA-ergic synaptic transmission in DCN as well as its plasticity are discussed. Studies indicate that fast inhibitory postsynaptic potentials (IPSPs) and currents (IPSCs) in neurons of DCN are mediated by GABAA receptors. While GABAB receptors are present in DCN, they do not appear to be activated by Purkinje cell axons. The IPSPs undergo paired-pulse, as well as frequency-dependent, depressions. In addition, tetanic stimulation of inputs can induce a long-term depression (LTD) of the IPSPs and IPSCs. Excitatory synapses do not appear to undergo long-term potentiation or LTD. The LTD of the IPSP is not input-specific, as it can be induced heterosynaptically and is associated with a reduced response of DCN neurons to a GABAA receptor agonist. Postsynaptic Ca2+ and protein phosphatases appear to contribute to the LTD. The N-methyl-D-aspartate receptor-gated, as well as the voltage-gated Ca2+ channels are proposed to be sources of the Ca2+. It is suggested that LTD of GABA-ergic transmission, by regulating DCN output, can modulate cerebellar function.
    Progress in Neurobiology 11/1997; 53(2):259-71. · 9.04 Impact Factor
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    ABSTRACT: A grease-gap recording technique which allows the monitoring of presynaptic d. c. potentials without contamination of potentials from postsynaptic elements was used to examine presynaptic actions of glutamate agonists in the CA1 region of rat hippocampus. Presynaptic depolarizations through the activation of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)- and 2-amino-5-phosphonovaleric acid (APV)-sensitive receptors could be induced by applied agonists. In addition, the N-methyl-D-aspartate (NMDA)-induced depolarization was smaller in the presence of extracellular Mg2+ suggesting some similarity to postsynaptic NMDA receptors. The (1S,3R)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (t-ACPD)-induced depolarization was antagonized by L-2-amino-3-phosphonopropionic acid (L-AP3) but was also sensitive to APV+CNQX, creating ambiguity as to the type of receptors involved. These results suggest that the activation of glutamate autoreceptors leads to a presynaptic depolarization.
    European Journal of Pharmacology 10/1995; 284(1-2):93-9. · 2.59 Impact Factor

Publication Stats

60 Citations
14.93 Total Impact Points

Institutions

  • 1995–2000
    • University of British Columbia - Vancouver
      • Department of Anesthesiology, Pharmacology and Therapeutics
      Vancouver, British Columbia, Canada