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

Chudomel, Ondřej; Herman, Howard; Nair, Kala P.; Moshé, Solomon L.; Galanopoulou, Aristea S.

doi:10.1016/j.neuroscience.2009.06.025

Cited by 37 publications

(37 citation statements)

References 52 publications

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“…There have been numerous reports of the kinetics of GABAergic events increasing over development (Hollrigel and Soltesz, 1997;Huntsman and Huguenard, 2000;Okada et al, 2000). Consistent with our findings for evoked responses in SNr neurons, recently Chudomel et al (2009) reported that the kinetics of spontaneous IPSCs in nigral neurons increase with age. Furthermore, the authors report an exchange of ␣3 subunits at perisomatic GABA A receptors with ␣1 subunits.…”

Section: Discussionsupporting

confidence: 93%

Differential Short-Term Plasticity at Convergent Inhibitory Synapses to the Substantia Nigra Pars Reticulata

Connelly¹,

Schulz²,

Lees³

et al. 2010

J. Neurosci.

129

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Inhibitory projections from the striatum and globus pallidus converge onto GABAergic projection neurons of the substantia nigra pars reticulata (SNr). Based on existing structural and functional evidence, these pathways are likely to differentially regulate the firing of SNr neurons. We sought to investigate the functional differences in inhibitory striatonigral and pallidonigral traffic using whole-cell voltage clamp in brain slices with these pathways preserved. We found that striatonigral IPSCs exhibited a high degree of paired-pulse facilitation. We tracked this facilitation over development and found the facilitation as the animal aged, but stabilized by postnatal day 17 (P17), with a paired pulse ratio of 2. We also found that the recovery from facilitation accelerated over development, again, reaching a stable phenotype by P17. In contrast, pallidonigral synapses show paired-pulse depression, and this depression could be solely explained by presynaptic changes. The mean paired-pulse ratio of 0.67 did not change over development, but the recovery from depression slowed over development. Pallidonigral IPSCs were significantly faster than striatonigral IPSCs when measured at the soma. Finally, under current clamp, prolonged bursts of striatal IPSPs were able to consistently silence the pacemaker activity of nigral neurons, whereas pallidal inputs depressed, allowing nigral neurons to reinstate firing. These findings highlight the importance of differential dynamics of neurotransmitter release in regulating the circuit behavior of the basal ganglia.

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Section: Discussionsupporting

confidence: 93%

Differential Short-Term Plasticity at Convergent Inhibitory Synapses to the Substantia Nigra Pars Reticulata

Connelly¹,

Schulz²,

Lees³

et al. 2010

J. Neurosci.

129

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“…We previously described that the properties of spontaneous inhibitory postsynaptic GABA A receptor (GABA A R) mediated currents (sIPSCs) in GABAergic neurons of the SNR A are age- and sex-dependent, in part explained by different types of α GABA A R subunits [8–11]. …”

Section: Introductionmentioning

confidence: 99%

Age- and Sex-Related Characteristics of Tonic Gaba Currents in the Rat Substantia Nigra Pars Reticulata

et al. 2015

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Previous studies have shown that the pharmacologic effects of GABAergic drugs and the postsynaptic phasic GABAAergic inhibitory responses in the anterior part of the rat substantia nigra pars reticulata (SNRA) are age- and sex-specific. Here, we investigate whether there are age- and sex-related differences in the expression of the δ GABAA receptor (GABAAR) subunit and GABAAR mediated tonic currents. We have used δ-specific immunochemistry and whole cell patch clamp to study GABAAR mediated tonic currents in the SNRA of male and female postnatal day (PN) PN5-9, PN11-16, and PN25-32 rats. We observed age-related decline, but no sex-specific changes, in bicuculline (BIM) sensitive GABAAR tonic current density, which correlated with the decline in δ subunit in the SNRA between PN15 and 30. Furthermore, we show that the GABAAR tonic currents can be modified by muscimol (GABAAR agonist; partial GABACR agonist), THIP (4,5,6,7-tetrahydroisoxazolo (5,4-c)pyridin-3-ol: α4β3δ GABAARs agonist and GABACR antagonist), and zolpidem (α1-subunit selective GABAAR agonist) in age-and sex-dependent manner specific for each drug. We propose that the emergence of the GABAAR-sensitive anticonvulsant effects of the rat SNRA during development may depend upon the developmental decline in tonic GABAergic inhibition of the activity of rat SNRA neurons, although other sex-specific factors are also involved.

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“…A developmental increase in perisomatic α1-ir and decrease in α3-ir was observed in both males and females, between PN5 and PN30 (Table 2). This developmental swap of α3 by α1 subunits is well known to occur in several brain regions, affecting the kinetics and drug sensitivity of GABA A R-IPSCs (Chudomel et al, 2009; Gingrich et al, 1995; Lavoie et al, 1997; Verdoorn, 1994). Indeed, in whole cell patch clamp experiments, the kinetics of IPSCs became faster with age and more responsive to the α1-preferring agonist zolpidem, consistent with the increase in α1-ir (Chudomel et al, 2009).…”

Section: Evidence For Sexual Dimorphism Of the Gabaar Expression In Tmentioning

confidence: 99%

“…This developmental swap of α3 by α1 subunits is well known to occur in several brain regions, affecting the kinetics and drug sensitivity of GABA A R-IPSCs (Chudomel et al, 2009; Gingrich et al, 1995; Lavoie et al, 1997; Verdoorn, 1994). Indeed, in whole cell patch clamp experiments, the kinetics of IPSCs became faster with age and more responsive to the α1-preferring agonist zolpidem, consistent with the increase in α1-ir (Chudomel et al, 2009). The only sex differences observed were a higher expression of α1-ir and α3-ir in female PN5 SNRa paralleled by a greater sensitivity of female PN5-9 SNRa neurons to zolpidem, compared with same age males.…”

Section: Evidence For Sexual Dimorphism Of the Gabaar Expression In Tmentioning

confidence: 99%

Sex dimorphism in seizure-controlling networks

Giorgi

Galanopoulou²,

Moshé

2014

Neurobiology of Disease

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Males and females show a different predisposition to certain types of seizures in clinical studies. Animal studies have provided growing evidence for sexual dimorphism of certain brain regions, including those that control seizures. Seizures are modulated by networks involving subcortical structures, including thalamus, reticular formation nuclei, and structures belonging to the basal ganglia. In animal models, the substantia nigra pars reticulata (SNR) is the best studied of these areas, given its relevant role in the expression and control of seizures throughout development in the rat. Studies with bilateral infusions of the GABAA receptor agonist muscimol have identified distinct roles of the anterior or posterior rat SNR in flurothyl seizure control, that follow sex-specific maturational patterns during development. These studies indicate that (a) the regional functional compartmentalization of the SNR appears only after the third week of life, (b) only the male SNR exhibits muscimol-sensitive proconvulsant effects which, in older animals, is confined to the posterior SNR, and (c) the expression of the muscimol-sensitive anticonvulsant effects become apparent earlier in females than in males. The first three postnatal days are crucial in determining the expression of the muscimol-sensitive proconvulsant effects of the immature male SNR, depending on the gonadal hormone setting. Activation of the androgen receptors during this early period seems to be important for the formation of this proconvulsant SNR region. We describe molecular/anatomical candidates underlying these age- and sex-related differences, as derived from in vitro and in vivo experiments, as well as by [14C]2-deoxyglucose autoradiography. These involve sex-specific patterns in the developmental changes in the structure or physiology or GABAA receptors or of other subcortical structures (e.g., locus coeruleus, hippocampus) that may affect the function of seizure-controlling networks.

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

Cited by 37 publications

References 52 publications

Differential Short-Term Plasticity at Convergent Inhibitory Synapses to the Substantia Nigra Pars Reticulata

Differential Short-Term Plasticity at Convergent Inhibitory Synapses to the Substantia Nigra Pars Reticulata

Age- and Sex-Related Characteristics of Tonic Gaba Currents in the Rat Substantia Nigra Pars Reticulata

Sex dimorphism in seizure-controlling networks

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