TY - JOUR
T1 - Presynaptic and postsynaptic GABAA receptors in rat suprachiasmatic nucleus
AU - Belenky, M. A.
AU - Sagiv, N.
AU - Fritschy, J. M.
AU - Yarom, Y.
PY - 2003/6/6
Y1 - 2003/6/6
N2 - The mammalian suprachiasmatic nucleus (SCN), the brain's circadian clock, is composed mainly of GABAergic neurons, that are interconnected via synapses with GABAA receptors. Here we report on the subcellular localization of these receptors in the SCN, as revealed by an extensively characterized antibody to the α3 subunit of GABAA receptors in conjunction with pre- and postembedding electron microscopic immunocytochemistry. GABAA receptor immunoreactivity was observed in neuronal perikarya, dendritic processes and axonal terminals. In perikarya and proximal dendrites, GABAA receptor immunoreactivity was expressed mainly in endoplasmic reticulum and Golgi complexes, while in the distal part of dendrites, immunoreaction product was associated with postsynaptic plasma membrane. Many GABAergic axonal terminals, as revealed by postembedding immunogold labeling, displayed GABAA receptor immunoreactivity, associated mainly with the extrasynaptic portion of their plasma membrane. The function of these receptors was studied in hypothalamic slices using whole-cell patch-clamp recording of the responses to minimal stimulation of an area dorsal to the SCN. Analysis of the evoked inhibitory postsynaptic currents showed that either bath or local application of 100 μM of GABA decreased GABAergic transmission, manifested as a two-fold increase in failure rate. This presynaptic effect, which was detected in the presence of the glutamate receptor blocker 6-cyano-7-nitroquinoxaline-2,3-dione and the selective GABAB receptor blocker CGP55845A, appears to be mediated via activation of GABAA receptors. Our results thus show that GABAA receptors are widely distributed in the SCN and may subserve both pre- and postsynaptic roles in controlling the mammalian circadian clock.
AB - The mammalian suprachiasmatic nucleus (SCN), the brain's circadian clock, is composed mainly of GABAergic neurons, that are interconnected via synapses with GABAA receptors. Here we report on the subcellular localization of these receptors in the SCN, as revealed by an extensively characterized antibody to the α3 subunit of GABAA receptors in conjunction with pre- and postembedding electron microscopic immunocytochemistry. GABAA receptor immunoreactivity was observed in neuronal perikarya, dendritic processes and axonal terminals. In perikarya and proximal dendrites, GABAA receptor immunoreactivity was expressed mainly in endoplasmic reticulum and Golgi complexes, while in the distal part of dendrites, immunoreaction product was associated with postsynaptic plasma membrane. Many GABAergic axonal terminals, as revealed by postembedding immunogold labeling, displayed GABAA receptor immunoreactivity, associated mainly with the extrasynaptic portion of their plasma membrane. The function of these receptors was studied in hypothalamic slices using whole-cell patch-clamp recording of the responses to minimal stimulation of an area dorsal to the SCN. Analysis of the evoked inhibitory postsynaptic currents showed that either bath or local application of 100 μM of GABA decreased GABAergic transmission, manifested as a two-fold increase in failure rate. This presynaptic effect, which was detected in the presence of the glutamate receptor blocker 6-cyano-7-nitroquinoxaline-2,3-dione and the selective GABAB receptor blocker CGP55845A, appears to be mediated via activation of GABAA receptors. Our results thus show that GABAA receptors are widely distributed in the SCN and may subserve both pre- and postsynaptic roles in controlling the mammalian circadian clock.
KW - Circadian clock
KW - Electrophysiology
KW - GABA
KW - GABA receptors
KW - Immunocytochemistry
KW - Suprachiasmatic nucleus
UR - http://www.scopus.com/inward/record.url?scp=0038066573&partnerID=8YFLogxK
U2 - 10.1016/S0306-4522(03)00062-9
DO - 10.1016/S0306-4522(03)00062-9
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
C2 - 12732237
AN - SCOPUS:0038066573
SN - 0306-4522
VL - 118
SP - 909
EP - 923
JO - Neuroscience
JF - Neuroscience
IS - 4
ER -