Dehydration-induced synaptic plasticity in magnocellular neurons of the hypothalamic supraoptic nucleus

Endocrinology. 2004 Nov;145(11):5141-9. doi: 10.1210/en.2004-0702. Epub 2004 Aug 5.


Norepinephrine plays a critical role in the regulation of hypothalamic neuroendocrine function, in large part through modulation of synaptic glutamate and gamma-aminobutyric acid (GABA) release. Hypothalamic magnocellular neuroendocrine cells undergo dramatic changes in synaptic organization under conditions of increased hormone release, including increased numbers of glutamatergic, GABAergic and noradrenergic synapses. We studied the functional plasticity of magnocellular neurons of the rat supraoptic nucleus induced by chronic dehydration using whole-cell recordings in hypothalamic slices. Dehydrated rats showed increases in glutamate and GABA release onto magnocellular neurons, as evidenced by an increase in the frequency of spontaneous excitatory (29%) and inhibitory (33%) postsynaptic currents. The change in glutamate release was likely due to increased numbers of release sites because paired-pulse facilitation analysis did not reveal a change in the probability of transmitter release. In untreated rats, norepinephrine facilitates glutamate release and attenuates GABA release onto magnocellular neurons. Dehydration resulted in a marked enhancement of norepinephrine's actions, doubling both the norepinephrine-induced increase in glutamate release and decrease in GABA release. The norepinephrine dose-response curve was shifted to the left with dehydration, revealing an increase in norepinephrine sensitivity. Thus, dehydration leads to an increase in glutamate and GABA release onto supraoptic magnocellular neurons as well as a marked enhancement of the facilitatory effect of norepinephrine on glutamate release and inhibitory effect on GABA release. This synaptic plasticity would be expected to increase the excitability of the magnocellular neurons and support the enhanced bursting capacity and facilitated hormone secretion observed in vivo with chronic dehydration.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Chronic Disease
  • Dehydration / physiopathology*
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • Glutamic Acid / metabolism
  • Male
  • Neuronal Plasticity / physiology*
  • Neurons / physiology
  • Norepinephrine / metabolism
  • Norepinephrine / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Supraoptic Nucleus / cytology
  • Supraoptic Nucleus / physiopathology*
  • Sympathomimetics / metabolism
  • Sympathomimetics / pharmacology
  • gamma-Aminobutyric Acid / metabolism


  • Sympathomimetics
  • Glutamic Acid
  • gamma-Aminobutyric Acid
  • Norepinephrine