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

O. Chudomel, H. Herman, K. Nair, Solomon L. Moshe, Aristea S. Galanopoulou

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21 Citations (Scopus)

Abstract

The responsiveness of the rat anterior substantia nigra pars reticulata (SNR) GABAergic neurons to GABAAergic 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 GABAARs-mediated inhibitory postsynaptic currents (sIPSCs) underlie these events, we studied sIPSCs at baseline and after application of the α1 GABAARs subunit selective agonist zolpidem, at postnatal days (PN) 5-9, PN12-15, and PN28-32. Results were correlated with the α1 and α3 GABAARs 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 α1-ir and decreased α3-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 α1-ir expression were the lowest in PN5-9 males but increased with age, in both genders. Our findings demonstrate that alterations in GABAARs 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 α1 expression suggests the existence of additional gender-specific factors that control the sIPSC kinetics in rat SNR.

Original languageEnglish (US)
Pages (from-to)155-167
Number of pages13
JournalNeuroscience
Volume163
Issue number1
DOIs
StatePublished - Sep 29 2009

Fingerprint

GABAergic Neurons
Inhibitory Postsynaptic Potentials
Synaptic Potentials
GABA-A Receptors
Immunochemistry
Pars Reticulata
Seizures
Observation
Neurons
Pharmaceutical Preparations

Keywords

  • development
  • immunohistochemistry
  • patch clamp
  • seizures
  • synaptic inhibition
  • zolpidem

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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title = "Age- and gender-related differences in GABAA receptor-mediated postsynaptic currents in GABAergic neurons of the substantia nigra reticulata in the rat",
abstract = "The responsiveness of the rat anterior substantia nigra pars reticulata (SNR) GABAergic neurons to GABAAergic 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 GABAARs-mediated inhibitory postsynaptic currents (sIPSCs) underlie these events, we studied sIPSCs at baseline and after application of the α1 GABAARs subunit selective agonist zolpidem, at postnatal days (PN) 5-9, PN12-15, and PN28-32. Results were correlated with the α1 and α3 GABAARs 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 α1-ir and decreased α3-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 α1-ir expression were the lowest in PN5-9 males but increased with age, in both genders. Our findings demonstrate that alterations in GABAARs 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 α1 expression suggests the existence of additional gender-specific factors that control the sIPSC kinetics in rat SNR.",
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T1 - Age- and gender-related differences in GABAA receptor-mediated postsynaptic currents in GABAergic neurons of the substantia nigra reticulata in the rat

AU - Chudomel, O.

AU - Herman, H.

AU - Nair, K.

AU - Moshe, Solomon L.

AU - Galanopoulou, Aristea S.

PY - 2009/9/29

Y1 - 2009/9/29

N2 - The responsiveness of the rat anterior substantia nigra pars reticulata (SNR) GABAergic neurons to GABAAergic 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 GABAARs-mediated inhibitory postsynaptic currents (sIPSCs) underlie these events, we studied sIPSCs at baseline and after application of the α1 GABAARs subunit selective agonist zolpidem, at postnatal days (PN) 5-9, PN12-15, and PN28-32. Results were correlated with the α1 and α3 GABAARs 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 α1-ir and decreased α3-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 α1-ir expression were the lowest in PN5-9 males but increased with age, in both genders. Our findings demonstrate that alterations in GABAARs 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 α1 expression suggests the existence of additional gender-specific factors that control the sIPSC kinetics in rat SNR.

AB - The responsiveness of the rat anterior substantia nigra pars reticulata (SNR) GABAergic neurons to GABAAergic 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 GABAARs-mediated inhibitory postsynaptic currents (sIPSCs) underlie these events, we studied sIPSCs at baseline and after application of the α1 GABAARs subunit selective agonist zolpidem, at postnatal days (PN) 5-9, PN12-15, and PN28-32. Results were correlated with the α1 and α3 GABAARs 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 α1-ir and decreased α3-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 α1-ir expression were the lowest in PN5-9 males but increased with age, in both genders. Our findings demonstrate that alterations in GABAARs 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 α1 expression suggests the existence of additional gender-specific factors that control the sIPSC kinetics in rat SNR.

KW - development

KW - immunohistochemistry

KW - patch clamp

KW - seizures

KW - synaptic inhibition

KW - zolpidem

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