Sex-dependent maturation of GABAA receptor-mediated synaptic events in rat substantia nigra reticulata

The substantia nigra pars reticulata (SNR) plays important roles in movement and, in an age- and sex-dependent manner, in seizure control. GABAergic synaptic transmission is critical in both normal development and seizures. In many neuronal types it is excitatory early in development and later switches to the mature hyperpolarizing type. We assessed the time course of the switch of GABAA receptor-mediated postsynaptic currents (PSCs) in anterior SNR neurons of male and female developing rats using the gramicidin perforated patch clamp technique. The switch occurred in males around postnatal day (PN) 17 and in females around PN10. This sex dimorphism may play a role in several other recognized sex differences in the development of SNR and in its regulatory role in seizures. © 2006

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

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. © 2006 Elsevier Inc. All rights reserved

The role of the substantia nigra pars reticulata in kindling resistance in rats with genetic absence epilepsy

WOS: 000363884100025PubMed ID: 26471261ObjectiveGenetic Absence Epilepsy Rats from Strasbourg (GAERS) show a resistance to secondary generalization of focal limbic seizures evoked by kindling. The substantia nigra pars reticulata (SNR) is involved in the propagation and modulation of seizures in kindling. We first examined the role of the SNRanterior and SNRposterior subregions in the resistance to the development of kindling in GAERS. Subsequently, to determine whether kindling resistance relates to differential sensitivity of -aminobutyric acid -aminobutyric acid (GABA)ergic or dopaminergic SNR neurons to kindling, we studied the effects of kindling-inducing stimulations on parvalbumin (PRV; GABAergic neuron marker) or tyrosine hydroxylase (TH; dopaminergic neuron marker) immunoreactivity (ir), respectively, in GAERS and in nonepileptic control (NEC) Wistar rats that lack kindling resistance. MethodsAdult male GAERS were implanted with a stimulation electrode in the amygdala, and bilateral injection cannulas for lidocaine or saline injection (30 min before each kindling stimulation until the animals reached three stage 5 seizures or the 22 stimulations) into the SNRanterior or SNRposterior. In another experiment, PRV-ir in SNRanterior and SNRposterior and TH-ir in SNRposterior only were densitometrically compared in GAERS-SHAM, NEC-SHAM GAERS-STIM, and NEC-STIM animals (6 kindling stimulations). ResultsBilateral SNRposterior infusions of lidocaine eliminated the kindling resistance and resulted in stage 5 generalized motor seizures in all kindled rats. Bilateral lidocaine infusions in the SNRanterior failed to alter the kindling resistance in GAERS. PRV-ir in the SNRposterior was unaltered in GAERS-STIM but increased in NEC-STIM group. Cellular TH-ir in the SNRposterior significantly increased by kindling stimulations in both NEC-STIM and GAERS-STIM groups. SignificanceThe kindling resistance in GAERS is mediated by the SNRposterior in a lidocaine-sensitive manner. The insensitivity to kindling stimulation of PRV-ir in SNRposterior of GAERS but not NEC rats, implicate GABAergic SNRposterior neurons in kindling resistance. In contrast, the observed stimulation-specific increase in TH-ir in the SNRposterior is unrelated to kindling resistance.Scientific and Technological Research Council of Turkey (TUBITAK) [111S209]; Marmara University Research Council; National Institute of Neurological Disorders and Stroke (NINDS) [NS078333, NS020253]; U.S. Department of Defense [W81XWH-13-1-0180]; Citizens United for Research in Epilepsy (CURE), UCB; Heffer Family Foundation; Barry Segal Family Foundation; Abbe Goldstein/Joshua Lurie and Laurie Marsh/Dan Levitz families; NINDS [NS078333, NS091170]; CURE, UCBThis study was supported by The Scientific and Technological Research Council of Turkey (TUBITAK), Project No: 111S209, and Marmara University Research Council. SLM received research grants from the National Institute of Neurological Disorders and Stroke (NINDS; NS078333, NS020253), U.S. Department of Defense (W81XWH-13-1-0180), Citizens United for Research in Epilepsy (CURE), UCB, the Heffer Family and Barry Segal Family Foundations, and the Abbe Goldstein/Joshua Lurie and Laurie Marsh/Dan Levitz families. ASG received research grants from NINDS (NS078333, NS091170), U.S. Department of Defense (W81XWH-13-1-0180), CURE, UCB, the Heffer Family and Barry Segal Family Foundations, and the Abbe Goldstein/Joshua Lurie and Laurie Marsh/Dan Levitz families

2017 International League Against Epilepsy classifications of seizures and epilepsy are steps in the right direction.

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