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Activation of Presynaptic GABA_B Receptors Modulates Synaptic Transmission in Rat Medial Geniculate Body

Author: LuoBin
Tutor: ChenLin
School: University of Science and Technology of China
Course: Biophysics
Keywords: Medial geniculate body Presynaptic GABA_B receptor Brain slice Whole-cell patch-clamp Postsynaptic current
CLC: R338
Type: PhD thesis
Year: 2011
Downloads: 64
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Abstract

The medial geniculate body (MGB) is an important relay neuclues of the auditory thalamus, it receives ascending inputs from the inferior colliculus and other subcortical neuclei and it also receives descending inputs from the auditory cortex.Metabotropic G-protein coupled GABAB receptors, like ionotropic GABAa and GABAC receptors, function as the inhibitory receptors in the nervous system. Activation of postsynaptic GABAB receptors can hyperpolarize neurons via potassium conductance mediated by specific inwardly rectifying K+channels (GIRK or Kir3), while activation of GABAB receptors in the presynaptic terminals results in inhibition of N-and P/Q-type voltage-gated Ca2+channels and consequently weakens the neurotransmission.In the MGB, the presence of GABAB receptors has been shown by morphological studies. Functional postsynaptic GABAB receptors in the MGB have been demonstrated by electrophysiological studies. However, the presence and physiological function of the presynaptic GABAB receptors in this nucleus have not been examined. Is there any difference of the modulation of presynaptic GABAB receptors on neurotransmission between the ascending and descending pathways? Does the activation of presynaptic GABAB receptors modulate inhibitory and excitatory neurotransmission differentially? Can endogenously released GABA activate presynaptic GABAB receptors and hence modulate neurotransmission? Is this modulation developmentally regulated? The present thesis tried to answer these questions with whole-cell patch-clamp recordings in brain slices of the rat. I electrically stimulated the ascending and descending inputs to MGB neurons with bipolar electrodes placed on the brachium of the inferior colliculus and the superior thalamic radiation; kynurenic acid or picrotoxin was added in the bath solution to record inhibitory postsynaptic currents (IPSCs) or excitatory postsynaptic currents (EPSCs). To isolate presynaptic mechanisms, I blocked the effects of postsynaptic GABAb receptors by filling recording electrodes with the internal solution containing cesium and QX-314. The major findings are as following:(1) Baclofen, a GABAB receptor agonist, reversibly suppressed both IPSCs and EPSCs and this suppressive effect could be blocked by CGP35348, a GABAB receptor antagonist demonstrating that the depressive effect of baclofen was mediated by activation of GABAB receptors,(2) baclofen significantly increased the ratio of IPSCs or EPSCs elicited by paired-pulse stimulation, suggesting a presynaptic mechanism involved,(3) there was no significant difference in the effect of baclofen on the EPSCs or the IPSCs between the ascending and descending pathways; however, baclofen had stronger suppression on the EPSCs than the IPSCs in either ascending or descending pathways,(4) baclofen depressed IPSCs and EPSCs in response to repetitive stimulation and slowed or reversed their decrease over the stimulus pulses Moreover, baclofen significantly increased normalized response, and (5) CGP55845, another GABAB receptor antagonist, increased the ratio of IPSCs to paired-pulse stimulation in young (P8-10) rats, although not in juvenile (P15-18) rats, suggesting that endogenously released GABA can activate presynaptic GABAB receptors and is which is developmentally regulated.The present study provides electrophysiological evidence for the presence of functional presynaptic GABAB receptors in the MGB and suggests an age-dependent role of these receptors in the synaptic transmission in this central auditory region.

Activation of Presynaptic GABA_B Receptors Modulates Synaptic Transmission in Rat Medial Geniculate Body

Abstract

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