GABAergic transmission in the rat paraventricular nucleus of the hypothalamus is suppressed by corticosterone and stress.
Parvocellular neurons in the hypothalamic paraventricular nucleus receive hormonal inputs mediated by corticosterone as well as neuronal inputs, prominent among which is a GABAergic inhibitory projection. In the present study we examined the functional properties of this GABAergic innervation when corticosteroid levels fluctuate. Frequency, amplitude and kinetic properties of miniature inhibitory postsynaptic potentials (mIPSCs), mediated by gamma amino butyric acid (GABA) were studied with whole cell recording in parvocellular neurons. Injection of a high dose of corticosterone in vivo suppressed the frequency but did not change the amplitude and kinetic properties of mIPSCs recorded 1-5 h later in vitro. Similar effects were observed after restraint stress. The corticosteroid actions do not require involvement of extrahypothalamic brain regions, because in vitro administration of 100 nM corticosterone (20 min) directly to a hypothalamic slice also suppressed the frequency of mIPSCs recorded several hours later. Corticosterone administration to hypothalamic slices from restraint rats did not result in stronger reduction of mIPSC frequency than either treatment alone, pointing to a common underlying mechanism. Paired pulse response inhibition was reduced by corticosterone, suggesting that the hormone decreases the release probability of GABA-containing vesicles. Unlike neurosteroids, corticosterone induced no rapid effects on mIPSC properties. These results indicate that increases in glucocorticoid level due to stress can slowly but persistently inhibit the GABAergic tone on parvocellular hypothalamic neurons via a hitherto unknown local mechanism independent of limbic projections.
Verkuyl
J Martin
JM
Swammerdam Institute for Life Sciences, section Neurobiology, University of Amsterdam, Kruislaan 320, 1098 SM Amsterdam, The Netherlands.
Karst
Henk
H
Joëls
Marian
M
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D003345:Corticosterone / Q000494:pharmacology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D016202:N-Methylaspartate / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects*; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology* / Q000187:drug effects; D018408:Patch-Clamp Techniques / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D012149:Restraint, Physical / Q000379:methods; D013312:Stress, Physiological; D009435:Synaptic Transmission / Q000187:drug effects*; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism* / Q000494:pharmacology
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D003345:Corticosterone