Age- and gender-related differences in GABAA receptor-mediated postsynaptic currents in GABAergic neurons of the substantia nigra reticulata in the rat

Neuroscience. 2009 Sep 29;163(1):155-67. doi: 10.1016/j.neuroscience.2009.06.025. Epub 2009 Jun 13.

Abstract

The responsiveness of the rat anterior substantia nigra pars reticulata (SNR) GABAergic neurons to GABA(A)ergic drugs changes with age and gender, altering its role in seizure control. To determine whether maturational and gender-specific differences in the properties of spontaneous GABA(A)Rs-mediated inhibitory postsynaptic currents (sIPSCs) underlie these events, we studied sIPSCs at baseline and after application of the alpha1 GABA(A)Rs subunit selective agonist zolpidem, at postnatal days (PN) 5-9, PN12-15, and PN28-32. Results were correlated with the alpha1 and alpha 3 GABA(A)Rs subunit immunoreactivity (-ir) at PN5, PN15, and PN30, using immunochemistry. The mean frequency, amplitude and charge transfer increased whereas the 10-90% rise time and decay time accelerated with age in both genders. The faster sIPSC kinetics in older rats were paralleled by increased alpha1-ir and decreased alpha 3-ir. At PN5-9, males had more robust sIPSCs (frequency, amplitude, charge carried per event and charge transfer) than females. At PN28-32, males exhibited higher amplitudes and faster kinetics than females. The zolpidem-induced increase of decay times, amplitude and charge transfer and alpha1-ir expression were the lowest in PN5-9 males but increased with age, in both genders. Our findings demonstrate that alterations in GABA(A)Rs subunit expression partially underlie age- and gender-specific sIPSC changes in SNR neurons. However, the observation of gender differences in sIPSC kinetics that cannot be attributed to changes in perisomatic alpha1 expression suggests the existence of additional gender-specific factors that control the sIPSC kinetics in rat SNR.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism
  • Animals
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Female
  • GABA Agonists / pharmacology
  • GABA-A Receptor Agonists
  • Immunohistochemistry
  • Inhibitory Postsynaptic Potentials / drug effects
  • Inhibitory Postsynaptic Potentials / physiology
  • Male
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Organ Culture Techniques
  • Patch-Clamp Techniques
  • Pyridines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, GABA-A / drug effects
  • Receptors, GABA-A / metabolism*
  • Sex Characteristics
  • Substantia Nigra / drug effects
  • Substantia Nigra / growth & development
  • Substantia Nigra / metabolism*
  • Synaptic Potentials / drug effects
  • Synaptic Potentials / physiology*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*
  • Zolpidem
  • gamma-Aminobutyric Acid / metabolism*

Substances

  • GABA Agonists
  • GABA-A Receptor Agonists
  • Gabra1 protein, rat
  • Gabra3 protein, rat
  • Pyridines
  • Receptors, GABA-A
  • gamma-Aminobutyric Acid
  • Zolpidem