Synaptic and membrane properties of neurons in the dorsomedial hypothalamus.
Studies in intact rats have shown that the dorsomedial hypothalamus (DMH) plays a key role in generating stress-induced physiologic changes, including activation of the hypothalamic-pituitary-adrenal axis through direct projections to paraventricular hypothalamic nucleus (PVN). However, little is known about the cellular properties of DMH neurons. We employed whole-cell patch-clamp recording techniques to characterize membrane properties and spontaneous post-synaptic currents (PSCs) in DMH neurons, including those projecting to PVN (identified by prior injection of DiI into PVN), in rat hypothalamic slices. DMH neurons (n=86 total) had uniform membrane properties. However, PVN-projecting neurons (n=32) had higher action potential (AP) thresholds, and fired fewer APs in response to current injection. Spontaneous PVN-projecting neurons (n=20) also fired APs at lower rates (4.8+/-0.6 Hz) than spontaneous neurons of unknown projection (n=38; 7.3+/-1.1 Hz). Spontaneous PSCs were observed in all neurons: One population expressed rapid decay characteristics (1.5-2.0 ms) and was blocked by non-NMDA ionotropic glutamate receptor antagonists NBQX or CNQX. Remaining PSCs reversed near E(Cl), were blocked by the GABA(A) receptor antagonists picrotoxin or bicuculline methiodide (BMI), and had longer decay time constants (4.5-6.0 ms) that were modulated by pentobarbital. Tetrodotoxin markedly reduced the frequency of PSCs sensitive to NBQX but not to BMI. Thus, DMH is made up of electrophysiologically similar neurons and PVN-projecting neurons are less excitable than neurons of unknown projection. Furthermore, as suggested by studies in intact rats, neurons in the DMH, including those projecting to the PVN, are regulated by tonic GABA(A) and non-NMDA glutamate receptor-mediated synaptic transmission.
Bailey
Timothy W
TW
Department of Pharmacology and Toxicology, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, IN 46202, USA.
Nicol
Grant D
GD
Schild
John H
JH
DiMicco
Joseph A
JA
D000596:Amino Acids / Q000493:pharmacokinetics; D000704:Analysis of Variance; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001640:Bicuculline / Q000031:analogs & derivatives* / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology*; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009431:Neural Conduction / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000596:Amino Acids; D000779:Anesthetics, Local; D001640:Bicuculline; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D010852:Picrotoxin; D013779:Tetrodotoxin; D014633:Valine; C098463:dolaisoleucine; C017069:bicuculline methiodide; C056639:2-amino-5-phosphopentanoic acid