Intracellular electrophysiological study of suprachiasmatic nucleus neurons in rodents: excitatory synaptic mechanisms.
1. To study the synaptic mechanisms of excitatory transmission in the suprachiasmatic nucleus (SCN), we assessed the effects of excitatory amino acid receptor antagonists on excitatory postsynaptic potentials (EPSPs) recorded from SCN neurons in horizontal and parasagittal hypothalamic slice preparations from rats and guinea-pigs. The EPSPs were evoked by electrical stimulation of either optic nerve or a site near the SCN. 2. When evoked at membrane potentials between -60 and -100 mV, the EPSPs from optic nerve stimulation were conventional in shape; they rose to the peak quickly (6.2 +/- 0.5 ms, mean +/- S.E.M.; n = 45) and decayed gradually over 50-250 ms. When evoked at membrane potentials between -20 and -55 mV after blockade of outward K+ currents and fast Na+ spikes by intracellular injection of Cs+ and QX-314 (n = 5 neurons), a slow depolarizing potential emerged near the fast peak of the EPSP. This slow potential, unlike the fast peak, was not linearly related to membrane potential. 3. An antagonist for kainate- and quisqualate-type excitatory amino acid receptors, 6,7-dinitroquinoxaline-2,3-dione (DNQX 1-10 microM), depressed in a concentration-dependent and reversible manner the EPSPs evoked by optic nerve stimulation at membrane potentials between -60 and -100 mV (n = 9). The effects of DNQX were not associated with any significant changes in the baseline input resistance or membrane potential of the postsynaptic neurons. The selective N-methyl-D-aspartate (NMDA) receptor antagonist, DL-2-amino-5-phosphonopentanoic acid (AP5, 50-100 microM), did not affect significantly and consistently the EPSPs evoked at these membrane potentials (n = 7). On the other hand, AP5 (50 microM) blocked or depressed the slow depolarizing component of the EPSPs evoked at membrane potentials between -20 and -55 mV (n = 4). No significant changes in baseline input resistance or membrane potential accompanied the effects of AP5. 4. Stimulation of a site lateral or dorsocaudal to the SCN evoked EPSPs distinct from those evoked by optic nerve stimulation. Again, DNQX (0.3-10 microM) depressed the EPSPs evoked at membrane potentials between -60 and -100 mV (n = 4) whereas AP5 (50 microM) had no effect (n = 5). When evoked at less negative membrane potentials (i.e. -20 to -55 mV) after intracellular injection of Cs+ and QX-314, the EPSPs had a slow depolarizing potential, similar to the EPSPs from optic nerve stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)
Mental Retardation Research Center, UCLA School of Medicine 90024.
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D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D004558:Electric Stimulation; D004594:Electrophysiology; D005071:Evoked Potentials / Q000187:drug effects*; D006168:Guinea Pigs; D008564:Membrane Potentials / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D009900:Optic Nerve / Q000502:physiology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D013493:Suprachiasmatic Nucleus / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission
D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; C056723:FG 9041; D015763:2-Amino-5-phosphonovalerate