Convergence of pre- and postsynaptic influences on glucosensing neurons in the ventromedial hypothalamic nucleus.
Glucosensing neurons in the ventromedial hypothalamic nucleus (VMN) were studied using visually guided slice-patch recording techniques in brain slices from 14- to 21-day-old male Sprague-Dawley rats. Whole-cell current-clamp recordings were made as extracellular glucose levels were increased (from 2.5 to 5 or 10 mmol/l) or decreased (from 2.5 to 0.1 mmol/l). Using these physiological conditions to define glucosensing neurons, two subtypes of VMN glucosensing neurons were directly responsive to alterations in extracellular glucose levels. Another three subtypes were not directly glucose-sensing themselves, but rather were presynaptically modulated by changes in extracellular glucose. Of the VMN neurons, 14% were directly inhibited by decreases in extracellular glucose (glucose-excited [GE]), and 3% were directly excited by decreases in extracellular glucose (glucose-inhibited [GI]). An additional 14% were presynaptically excited by decreased glucose (PED neurons). The other two subtypes of glucosensing neurons were either presynaptically inhibited (PIR; 11%) or excited (PER; 8%) when extracellular glucose was raised to > 2.5 mmol/l. GE neurons sensed decreased glucose via an ATP-sensitive K(+) (K(ATP)) channel. The inhibitory effect of increased glucose on PIR neurons appears to be mediated by a presynaptic gamma-aminobutyric acid-ergic glucosensing neuron that probably originates outside the VMN. Finally, all types of glucosensing neurons were both fewer in number and showed abnormal responses to glucose in a rodent model of diet-induced obesity and type 2 diabetes.
Song
Z
Z
Department of Pharmacology and Physiology, New Jersey Medical School (UMDNJ), Newark, New Jersey 07103, USA.
Levin
B E
BE
McArdle
J J
JJ
Bakhos
N
N
Routh
V H
VH
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002452:Cell Count; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology / Q000503:physiopathology*; D004032:Diet; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D009765:Obesity / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000502:physiology*; D014697:Ventromedial Hypothalamic Nucleus / Q000473:pathology / Q000503:physiopathology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D015221:Potassium Channels; D005680:gamma-Aminobutyric Acid; D000255:Adenosine Triphosphate; D005947:Glucose