Evidence for a GABAergic nigrothalamic pathway in the rat

Macleod, Neil; James, Thomas A.; Kilpatrick, Ian C.; Starr, Michael S.

doi:10.1007/bf00236662

Cited by 161 publications

(46 citation statements)

References 27 publications

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“…Our study confirms these earlier studies by demonstrating the dense innervation present in the ventral thalamic region. The observation that the SN inhibits the VPL is also consistent with numerous studies that have established that the net effect of SN activation is the inhibition of relay neurons in the thalamus, and that reductions in the spontaneous firing of SNR neurons result in the reduction of GABA release and the disinhibition of thalamic neurons (Ueki et al, 1977;MacLeod et al, 1980;Timmerman and Westerink, 1997).…”

Section: Sn Inhibits Vplsupporting

confidence: 85%

“…The SN also contains dopaminergic neurons in the pars compacta (SNC) that modulate synapses and excitability in the thalamus (Lavin and Grace, 1998;Sánchez-González et al, 2005;Yagüe et al, 2013). SNR neurons fire spontaneously at 30 -60 Hz, and the prevailing view is that they tonically inhibit thalamic neurons MacLeod et al, 1980;Chevalier andDeniau, 1984, 1990;Chevalier et al, 1985;Deniau et al, 2007;Berényi et al, 2009). Suppression of SNR activity disinhibits the thalamus, and thereby elevates thalamic and cortical activity (Chevalier andDeniau, 1984, 1990;Chevalier et al, 1985;Deniau et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

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The Substantia Nigra Conveys Target-Dependent Excitatory and Inhibitory Outputs from the Basal Ganglia to the Thalamus

Antal

Beneduce

Regehr

2014

Journal of Neuroscience

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The basal ganglia (BG), which influence cortical activity via the thalamus, play a major role in motor activity, learning and memory, sensory processing, and many aspects of behavior. The substantia nigra (SN) consists of GABAergic neurons of the pars reticulata that inhibit thalamic neurons and provide the primary output of the BG, and dopaminergic neurons of the pars compacta that modulate thalamic excitability. Little is known about the functional properties of the SN3thalamus synapses, and anatomical characterization has been controversial. Here we use a combination of anatomical, electrophysiological, genetic, and optogenetic approaches to re-examine these synaptic connections in mice. We find that neurons in the SN inhibit neurons in the ventroposterolateral nucleus of the thalamus via GABAergic synapses, excite neurons in the thalamic nucleus reticularis, and both excite and inhibit neurons within the posterior nucleus group. Glutamatergic SN neurons express the vesicular glutamate receptor transporter vGluT2 and receive inhibitory synapses from striatal neurons, and many also express tyrosine hydroxylase, a marker of dopaminergic neurons. Thus, in addition to providing inhibitory outputs, which is consistent with the canonical circuit, the SN provides glutamatergic outputs that differentially target thalamic nuclei. This suggests that an increase in the activity of glutamatergic neurons in the SN allows the BG to directly excite neurons in specific thalamic nuclei. Elucidating an excitatory connection between the BG and the thalamus provides new insights into how the BG regulate thalamic activity, and has important implications for understanding BG function in health and disease.

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Section: Sn Inhibits Vplsupporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

The Substantia Nigra Conveys Target-Dependent Excitatory and Inhibitory Outputs from the Basal Ganglia to the Thalamus

Antal

Beneduce

Regehr

2014

Journal of Neuroscience

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“…L-DOPA and J-113397 reduced GABA release in the VMTh (experiment 5) SNr is known to send GABAergic projections to the VMTh (Di Chiara et al, 1979;MacLeod et al, 1980), which represents the motor output of the basal ganglia. Thus, we hypothesized that the attenuation of motor disabilities could be associated with inhibition of nigrothalamic transmission.…”

Section: Interaction Between Submaximal Doses (Experiments 3)mentioning

confidence: 99%

“…To investigate the mechanisms underlying this interaction, GLU and GABA release was analyzed by microdialysis in the SNr of rats undergoing behavioral testing (bar test; experiment 4). To determine whether changes in SNr neurotransmitter release correlated with changes of activity of nigrothalamic GABAergic neurons (i.e., the basal ganglia motor output), GABA release was also measured in the ventromedial thalamus (VMTh) (experiment 5), one of the main targets of nigrothalamic GABAergic neurons (Di Chiara et al, 1979;MacLeod et al, 1980). Finally, to confirm that both antiakinetic action and the changes in thalamic GABA release after J-113397 and L-DOPA coadministration were attributable to inhibition of nigrothalamic GABAergic transmission, neurochemical and behavioral analysis were performed during reverse dialysis of the voltage-dependent Na ϩ channel blocker tetrodotoxin (TTX) (experiment 6) or the GABA A receptor antagonist bicuculline (experiment 7) in the SNr.…”

Section: Introductionmentioning

confidence: 99%

The Nociceptin/Orphanin FQ Receptor Antagonist J-113397 and l-DOPA Additively Attenuate Experimental Parkinsonism through Overinhibition of the Nigrothalamic Pathway

Marti¹,

Trapella²,

Viaro³

et al. 2007

J. Neurosci.

126

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By using a battery of behavioral tests, we showed that nociceptin/orphanin FQ receptor (NOP receptor) antagonists attenuated parkinsonian-like symptoms in 6-hydroxydopamine hemilesioned rats (Marti et al., 2005). We now present evidence that coadministration of the NOP receptor antagonist 1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1,3-dihydro-2H benzimidazol-2-one (J-113397) and L-DOPA to 6-hydroxydopamine hemilesioned rats produced an additive attenuation of parkinsonism. To investigate the neurobiological substrates underlying this interaction, in vivo microdialysis was used in combination with behavioral measurements (bar test). J-113397 and L-DOPA alone reduced the time on bars (i.e., attenuated akinesia) and elevated GABA release selectively in the lesioned substantia nigra reticulata. J-113397 also reduced nigral glutamate levels, whereas L-DOPA was ineffective. J-113397 and L-DOPA coadministration produced additive antiakinetic effect, which was associated with additive increase in nigral GABA release but no additional reductions in glutamate levels. To investigate whether the increase in nigral GABA release could translate to changes in nigrothalamic transmission, GABA release was monitored in the ventromedial thalamus (one of the main target areas of the nigrothalamic projections). J-113397 and L-DOPA decreased thalamic GABA release and attenuated akinesia, their combination resulting in a more profound effect. These actions were prevented by perfusing the voltage-dependent Na ϩ channel blocker tetrodotoxin or the GABA A receptor antagonist bicuculline in the substantia nigra reticulata. These data demonstrate that J-113397 and L-DOPA exert their antiparkinsonian action through overinhibition of nigrothalamic transmission and suggest that NOP receptor antagonists may be useful as an adjunct to L-DOPA therapy for Parkinson's disease.

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“…Evidence for converging projections of basal ganglia and cerebellum in rodents can be found in several electrophysiological studies (MacLeod et al 1980;Chevalier and Deniau 1982;Buee et al 1986;MacLeod and James 1984). MacLeod et al (1980) placed stimulating electrodes in various areas and extracellularly recorded the spiking behavior in VM and Pf neurons.…”

Section: Rats Electrophysiological Evidencementioning

confidence: 99%

Thalamic interactions of cerebellum and basal ganglia

2017

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Cerebellum and basal ganglia are reciprocally interconnected with the neocortex via oligosynaptic loops. The signal pathways of these loops predominantly converge in motor areas of the frontal cortex and are mainly segregated on subcortical level. Recent evidence, however, indicates subcortical interaction of these systems. We have reviewed literature that addresses the question whether, and to what extent, projections of main output nuclei of basal ganglia (reticular part of the substantia nigra, internal segment of the globus pallidus) and cerebellum (deep cerebellar nuclei) interact with each other in the thalamus. To this end, we compiled data from electrophysiological and anatomical studies in rats, cats, dogs, and non-human primates. Evidence suggests the existence of convergence of thalamic projections originating in basal ganglia and cerebellum, albeit sparse and restricted to certain regions. Four regions come into question to contain converging inputs: (1) lateral parts of medial dorsal nucleus (MD); (2) parts of anterior intralaminar nuclei and centromedian and parafascicular nuclei (CM/Pf); (3) ventromedial nucleus (VM); and (4) border regions of cerebellar and ganglia terminal territories in ventral anterior and ventral lateral nuclei (VA-VL). The amount of convergences was found to exhibit marked interspecies differences. To explain the rather sparse convergences of projection territories and to estimate their physiological relevance, we present two conceivable principles of anatomical organization: (1) a "core-and-shell" organization, in which a central core is exclusive to one projection system, while peripheral shell regions intermingle and occasionally converge with other projection systems and (2) convergences that are characteristic to distinct functional networks. The physiological relevance of these convergences is not yet clear. An oculomotor network proposed in this work is an interesting candidate to examine potential ganglia and cerebellar subcortical interactions.

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Evidence for a GABAergic nigrothalamic pathway in the rat

Cited by 161 publications

References 27 publications

The Substantia Nigra Conveys Target-Dependent Excitatory and Inhibitory Outputs from the Basal Ganglia to the Thalamus

The Substantia Nigra Conveys Target-Dependent Excitatory and Inhibitory Outputs from the Basal Ganglia to the Thalamus

The Nociceptin/Orphanin FQ Receptor Antagonist J-113397 and l-DOPA Additively Attenuate Experimental Parkinsonism through Overinhibition of the Nigrothalamic Pathway

Thalamic interactions of cerebellum and basal ganglia

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