Chronic stress attenuates GABAergic inhibition and alters gene expression of parvocellular neurons in rat hypothalamus

JM Verkuyl, SE Hemby, M Joels*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

112 Citations (Scopus)

Abstract

Chronic stress causes disinhibition of the hypothalamus-pituitary-adrenal axis. Consequently, the brain is overexposed to glucocorticoids which in humans may precipitate stress-related disorders, e.g. depression. The hypothalamus-pituitary-adrenal activity is strongly regulated by GABAergic input to parvocellular neurons in the hypothalamic paraventricular nucleus. We here report a reduced frequency of miniature inhibitory postsynaptic currents (mIPSCs) in parvocellular neurons of rats exposed to 3 weeks of unpredictable stress. The mIPSC amplitude and kinetic properties were unchanged, pointing to a presynaptic change caused by chronic stress. Because paired-pulse inhibition was unaffected by chronic stress, the number of functional GABAergic synaptic contacts rather than the release probability seems to be reduced after chronic stress. Linearly amplified RNA from postsynaptic cells was hybridized with multiple cDNA clones of interest, including most GABA(A) receptor subunits. In agreement with the electrophysiological observations, relative expression of the prevalent GABA(A)alpha1, alpha3, gamma1 and gamma2 receptor subunits, which largely contribute to the recorded responses, was not altered after chronic stress. However, expression of the extra-synaptic GABA(A)alpha5 subunit, earlier linked to depression in humans, and of the delta receptor subunit were found to be significantly changed. In conclusion, chronic stress leads to presynaptic functional alterations in GABAergic input to the paraventricular nucleus which could contribute to the observed disinhibition of the hypothalamus-pituitary-adrenal axis; additionally other aspects of GABAergic transmission may also be changed due to transcriptional regulation of specific receptor subunits in the parvocellular neurons.

Original languageEnglish
Pages (from-to)1665-1673
Number of pages9
JournalEuropean Journal of Neuroscience
Volume20
Issue number6
DOIs
Publication statusPublished - Sep-2004
Externally publishedYes

Keywords

  • corticosterone
  • evoked response
  • miniature inhibitory postsynaptic current
  • single cell RNA amplification
  • whole cell voltage clamp
  • PITUITARY-ADRENAL AXIS
  • RECEPTOR SUBUNIT EXPRESSION
  • DENTATE GRANULE CELLS
  • CA1 PYRAMIDAL NEURONS
  • GABA(A) RECEPTOR
  • PARAVENTRICULAR NUCLEUS
  • DELTA-SUBUNIT
  • POSTSYNAPTIC CURRENTS
  • NEUROSTEROID MODULATION
  • ADRENOCORTICAL AXIS

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