Presynaptic inhibition by baclofen of retinohypothalamic excitatory synaptic transmission in rat suprachiasmatic nucleus.
Optic nerve stimulation evoked monosynaptic excitatory postsynaptic currents in suprachiasmatic nucleus neurons maintained in vitro. These currents were completely blocked by a combination of glutamate receptor antagonists, 6-cyano-7-nitroquinoxaline-2,3-dione and 4-aminophosphonovaleric acid. Stimulation of the ipsilateral or contralateral suprachiasmatic nucleus produced a biphasic response consisting of an excitatory postsynaptic current followed by an bicuculline-sensitive inhibitory postsynaptic current. Most suprachiasmatic nucleus neurons had spontaneous inhibitory and excitatory synaptic currents produced by action potential-independent and, less frequently, action potential-dependent release of GABA and glutamate. Baclofen reversibly reduced the amplitude of excitatory postsynaptic currents evoked by optic nerve stimulation and the effect was antagonized by 2-hydroxysaclofen. In addition, baclofen reduced the frequency but not the amplitude of the spontaneous miniature excitatory postsynaptic currents. In a subset of suprachiasmatic nucleus neurons, baclofen induced an outward current, probably by increasing a potassium conductance. Baclofen had no effect on either evoked or spontaneous inhibitory postsynaptic currents or on currents activated by pulse application of glutamate. These data indicate that activation of GABAB receptors can inhibit suprachiasmatic nucleus neurons by two mechanisms. The first is to inhibit the release of glutamate from terminals of the retinohypothalamic tract. The second is the postsynaptic activation of a potassium conductance in a portion of these neurons.
Jiang
Z G
ZG
Vollum Institute for Advanced Biomedical Research, Oregon Health Sciences University, Portland 97201-3098, USA.
Allen
C N
CN
North
R A
RA
D015763:2-Amino-5-phosphonovalerate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D001640:Bicuculline; D004594:Electrophysiology; D018698:Glutamic Acid / Q000187:drug effects; D008297:Male; D009897:Optic Chiasm / Q000502:physiology; D009900:Optic Nerve / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000502:physiology; D013493:Suprachiasmatic Nucleus / Q000187:drug effects* / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D018080:Receptors, GABA-B; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D001418:Baclofen; D001640:Bicuculline