Changes in firing rate and pattern of GABAergic neurons in subregions of the substantia nigra pars reticulata in rat models of Parkinson's disease

Wang, Yong; Zhang, Qiao Jun; Liu, Jian; Ali, Umar; Gui, Zhen; Hui, Yan Ping; Chen, Li; Wang, Tao

doi:10.1016/j.brainres.2010.02.008

Cited by 38 publications

(36 citation statements)

References 32 publications

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“…As shown previously, bath application of the GABA B receptor agonist baclofen (5 μM) induced membrane hyperpolarization (Fig 1B). Sustained uncaging of Rubi-GABA (5 μM) in the presence of the GABA A receptor antagonist SR-95531 (gabazine, 25 μM) [44,45] also induced a consistent membrane hyperpolarization (Fig 1D). These effects are in agreement with the previously described coupling of GABA B receptors through G i/o proteins to K ir 3 K + channels [30,46].…”

Section: Resultsmentioning

confidence: 99%

Transient Activation of GABAB Receptors Suppresses SK Channel Currents in Substantia Nigra Pars Compacta Dopaminergic Neurons

et al. 2016

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Dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc) are richly innervated by GABAergic neurons. The postsynaptic effects of GABA on SNc DA neurons are mediated by a mixture of GABAA and GABAB receptors. Although activation of GABAA receptors inhibits spike generation, the consequences of GABAB receptor activation are less well characterized. To help fill this gap, perforated patch recordings were made from young adult mouse SNc DA neurons. Sustained stimulation of GABAB receptors hyperpolarized SNc DA neurons, as previously described. However, transient stimulation of GABAB receptors by optical uncaging of GABA did not; rather, it reduced the opening of small-conductance, calcium-activated K+ (SK) channels and increased the irregularity of spiking. This modulation was attributable to inhibition of adenylyl cyclase and protein kinase A. Thus, because suppression of SK channel activity increases the probability of burst spiking, transient co-activation of GABAA and GABAB receptors could promote a pause-burst pattern of spiking.

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Section: Resultsmentioning

confidence: 99%

Transient Activation of GABAB Receptors Suppresses SK Channel Currents in Substantia Nigra Pars Compacta Dopaminergic Neurons

et al. 2016

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“…We hypothesize that the diverse impairments characteristic of pathological disruption of basal ganglia function could reflect, in part, a control system operating outside of a stable regime. Although there is evidence of perturbed dynamics in the SNr in disease models (Ibanez-Sandoval et al, 2007; Samadi et al, 2008; Wang et al, 2010), the specific contribution of the intranigral microcircuit to the diverse behavioral impairments observed in diseases afflicting the basal ganglia circuit remains unclear.…”

Section: Discussionmentioning

confidence: 99%

The inhibitory microcircuit of the substantia nigra provides feedback gain control of the basal ganglia output

Brown

Pan

Dudman

2014

eLife

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Dysfunction of the basal ganglia produces severe deficits in the timing, initiation, and vigor of movement. These diverse impairments suggest a control system gone awry. In engineered systems, feedback is critical for control. By contrast, models of the basal ganglia highlight feedforward circuitry and ignore intrinsic feedback circuits. In this study, we show that feedback via axon collaterals of substantia nigra projection neurons control the gain of the basal ganglia output. Through a combination of physiology, optogenetics, anatomy, and circuit mapping, we elaborate a general circuit mechanism for gain control in a microcircuit lacking interneurons. Our data suggest that diverse tonic firing rates, weak unitary connections and a spatially diffuse collateral circuit with distinct topography and kinetics from feedforward input is sufficient to implement divisive feedback inhibition. The importance of feedback for engineered systems implies that the intranigral microcircuit, despite its absence from canonical models, could be essential to basal ganglia function. DOI: http://dx.doi.org/10.7554/eLife.02397.001

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“…Ideally, one would like to study the function of SN neurons in healthy human subjects, but at present such recordings may not be ethically obtained in any other human population. Converging evidence from histochemical (Damier et al, 1999b) and electrophysiological studies (Zaghloul et al, 2009; Ramayya et al, 2014) in patients with Parkinson's disease and in animals (Hollerman and Grace, 1990; Zigmond et al, 1990; Wang et al, 2010) indicate that a significant population of viable DA neurons remain in the Parkinsonian SN. We suggest that the observed DA and GABA responses reflect activity from the subpopulation of healthy neurons that remain in the SN.…”

Section: Discussionmentioning

confidence: 99%

Electrophysiological evidence for functionally distinct neuronal populations in the human substantia nigra

Ramayya

Zaghloul

Weidemann

et al. 2014

Front. Hum. Neurosci.

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The human substantia nigra (SN) is thought to consist of two functionally distinct neuronal populations—dopaminergic (DA) neurons in the pars compacta subregion and GABA-ergic neurons in the pars reticulata subregion. However, a functional dissociation between these neuronal populations has not previously been demonstrated in the awake human. Here we obtained microelectrode recordings from the SN of patients undergoing deep brain stimulation (DBS) surgery for Parkinson's disease as they performed a two-alternative reinforcement learning task. Following positive feedback presentation, we found that putative DA and GABA neurons demonstrated distinct temporal dynamics. DA neurons demonstrated phasic increases in activity (250–500 ms post-feedback) whereas putative GABA neurons demonstrated more delayed and sustained increases in activity (500–1000 ms post-feedback). These results provide the first electrophysiological evidence for a functional dissociation between DA and GABA neurons in the human SN. We discuss possible functions for these neuronal responses based on previous findings in human and animal studies.

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Changes in firing rate and pattern of GABAergic neurons in subregions of the substantia nigra pars reticulata in rat models of Parkinson's disease

Cited by 38 publications

References 32 publications

Transient Activation of GABAB Receptors Suppresses SK Channel Currents in Substantia Nigra Pars Compacta Dopaminergic Neurons

Transient Activation of GABAB Receptors Suppresses SK Channel Currents in Substantia Nigra Pars Compacta Dopaminergic Neurons

The inhibitory microcircuit of the substantia nigra provides feedback gain control of the basal ganglia output

Electrophysiological evidence for functionally distinct neuronal populations in the human substantia nigra

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