Hippocampal and hypothalamic function after chronic stress

M Joels*, JM Verkuyl, E Van Riel

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingConference contributionAcademicpeer-review

30 Citations (Scopus)

Abstract

Hyperactivity of the hypothalamo-pituitary-adrenal (HPA) axis is often observed in association with and even prior to the onset of major depression. It is presently unclear (1) which molecular and cellular processes contribute to hyperactivity of parvocellular hypothalamic neurons (key regulators of the HPA system) and (2) how HPA axis hyperactivity can lead to attenuation of central serotonergic transmission, a crucial factor in the onset of clinical symptoms. In an attempt to address these issues in an experimental model we used rats exposed to chronic unpredictable stressors, a paradigm causing prolonged HPA-axis hyperactivity. In the first study spontaneous and evoked GABA-mediated input to parvocellular neurons in the paraventricular hypothalamic nucleus was recorded with the whole cell patch-clamp technique. The frequency, but not other properties, of spontaneous GABA-mediated inhibitory postsynaptic currents was reduced after chronic stress, resulting in a reduced amplitude of the evoked GABA current. This potentially would disinhibit parvocellular neurons, provided that other inputs are unchanged. In the second study, responses of CA1 hippocampal neurons to serotonin were recorded with microelectrodes. It appeared that the membrane hyperpolarization caused by activation of serotonin-1A receptors is attenuated in tissue from chronically stressed rats. However, no apparent changes in expression of the serotonin-1A or corticosteroid receptors were observed. This supports the notion that chronic stress eventually results in attenuation of serotonergic responsiveness by a mechanism not involving transcriptional regulation of the receptor. Follow-up studies will need to examine whether treatment with corticosteroid receptor antagonists can normalize the attenuated transmission after chronic stress.

Original languageEnglish
Title of host publicationSTEROIDS AND THE NERVOUS SYSTEM
EditorsG Panzica, RC Melcangi
PublisherNew York Academy of Sciences
Pages367-378
Number of pages12
ISBN (Print)1-57331-486-2
DOIs
Publication statusPublished - 2003
Externally publishedYes
Event2nd International Meeting on Steroids and the Nervous System - Turin, Italy
Duration: 22-Feb-200326-Feb-2003

Publication series

NameANNALS OF THE NEW YORK ACADEMY OF SCIENCES
PublisherNEW YORK ACAD SCIENCES
Volume1007
ISSN (Print)0077-8923

Conference

Conference2nd International Meeting on Steroids and the Nervous System
Country/TerritoryItaly
CityTurin
Period22/02/200326/02/2003

Keywords

  • corticosterone
  • electrophysiology
  • GABA
  • serotonin
  • depression
  • PITUITARY-ADRENAL AXIS
  • CORTICOSTEROID RECEPTOR BALANCE
  • PYRAMIDAL NEURONS
  • GLUCOCORTICOID RECEPTOR
  • GENE-EXPRESSION
  • PARAVENTRICULAR NUCLEUS
  • MEDIATED RESPONSE
  • GABA(A) RECEPTOR
  • APICAL DENDRITES
  • RAT HIPPOCAMPUS

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