The role of substantia nigra pars reticulata in modulating clonic seizures is determined by testosterone levels during the immediate postnatal period

Filippo S. Giorgi, Jana Velíšková, Ondřej Chudomel, Andreas Kyrozis, Solomon L. Moshé

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

GABAergic activation of substantia nigra pars reticulata (SNR) at postnatal day (PN) 15 has sex-specific features on seizure control in vivo and electrophysiological responses in vitro. In males, the GABAA-receptor agonist muscimol has proconvulsant effects and induces depolarizing responses. In females, muscimol has no effect on seizures and evokes hyperpolarizing responses. We determined the time period during which sex hormones must be present to produce the sex-specific muscimol effects on seizures and their influence on SNR GABAA receptor-mediated postsynaptic currents. Exposure to testosterone or its metabolites (estrogen or dihydrotestosterone) during PN0-2 in females or males castrated at PN0 was sufficient to produce proconvulsant muscimol effects but did not affect the in vitro GABA responses, which remained hyperpolarizing. The data suggest that the PN0-2 period is critical for the development of the seizure-controlling SNR system; the hormonal effect on seizure control is independent from their effect on GABA conductance.

Original languageEnglish (US)
Pages (from-to)73-79
Number of pages7
JournalNeurobiology of Disease
Volume25
Issue number1
DOIs
StatePublished - Jan 1 2007

Keywords

  • GABA
  • Muscimol infusions
  • Patch clamp
  • Seizure
  • Sex hormones
  • Substantia nigra

ASJC Scopus subject areas

  • Neurology

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