Evidence for a gabaergic projection from the substantia nigra to the ventromedial thalamus and to the superior colliculus of the rat

Chiara, G. Di; Porceddu, M.L.; Morelli, Micaela; Mulas, Ml; Gessa, G L

doi:10.1016/0006-8993(79)90983-1

Cited by 381 publications

(101 citation statements)

References 30 publications

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“…The co-activation of the VM during the pre-clonic state could be caused by changes in the SNR posterior , perhaps reflecting GABA or acetylcholine release through abundant GABAergic and cholinergic projection neurons (Di Chiara et al, 1979;Kha et al, 2001). However, pharmacological and lesion studies showed no involvement of VM in seizure control (Garant et al, 1993;Moshé et al, 1985).…”

Section: Discussionmentioning

confidence: 99%

Regional neural activity within the substantia nigra during peri-ictal flurothyl generalized seizure stages

Velı́šková

Miller

Nunes

et al. 2005

Neurobiology of Disease

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Structures responsible for the onset, propagation, and cessation of generalized seizures are not known. Lesion and microinfusion studies suggest that the substantia nigra pars reticulata (SNR) seizurecontrolling network could play a key role. However, the expression of neural activity within the SNR and its targets during discrete pre-and postictal periods has not been investigated. In rats, we used flurothyl to induce generalized seizures over a controlled time period and 2-deoxyglucose autoradiography mapping technique. Changes in neural activity within the SNR were region-specific. The SNR posterior was selectively active during the pre-clonic period and may represent an early gateway to seizure propagation. The SNR anterior and superior colliculus changed their activity during progression to tonic-clonic seizure, suggesting the involvement in coordinated regional activity that results in inhibitory effects on seizures. The postictal suppression state was correlated with changes in the SNR projection targets, specifically the pedunculopontine tegmental nucleus and superior colliculus.

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Section: Discussionmentioning

confidence: 99%

Regional neural activity within the substantia nigra during peri-ictal flurothyl generalized seizure stages

Velı́šková

Miller

Nunes

et al. 2005

Neurobiology of Disease

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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: 98%

“…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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Section: Abstract: Startle; Superior Colliculus; Bicuculline; Muscimmentioning

confidence: 99%

“…The deep SC/Me is a major target of the SNr (Faull and Mehler, 1978) and has a direct projection to the reticular formation where cells in the PnC are located (Meloni and Davis, 1999b). A number of studies have shown that the nigrotectal projection contains GABA (Di Chiara et al, 1979;Araki et al, 1984), and blockade of GABA transmission in the deep SC/Me elicits a constellation of motor behaviors, including an explosive jumping behavior Cools et al, 1983).On the basis of the above data and the observation that GABA levels are reduced in the deep SC/Me after systemic administration of dopamine agonists (Melis and Gale, 1983), we hypothesized that removal of GABA tone in this area may (1) enhance the acoustic startle response by itself and (2) mediate the enhancement of startle seen after systemic administration of D 1 agonists. To test the first hypothesis, we locally infused animals with the GABA A antagonist bicuculline into the deep SC/Me and tested them for their acoustic startle response.…”

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confidence: 99%

GABA in the Deep Layers of the Superior Colliculus/Mesencephalic Reticular Formation Mediates the Enhancement of Startle by the Dopamine D₁Receptor Agonist SKF 82958 in Rats

Meloni

Davis

2000

J. Neurosci.

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GABA transmission in the deep layers of the superior colliculus/ deep mesencephalic reticular formation (deep SC/Me) mediates several motor responses, including those expressed after systemic administration of dopamine agonists. In the present study we examined the role of the deep SC/Me in the modulation of the acoustic startle reflex and its enhancement by the dopamine D 1 agonist SKF 82958. Rats were implanted with bilateral cannulas into the deep SC/Me or superficial layers of the SC (super SC) and 1 week later were infused with various compounds. The GABA A antagonist bicuculline (0, 5, and 10 ng) produced a doseand time-dependent enhancement of startle after infusion into the deep SC/Me, but not the super SC. Infusion of the GABA A agonist muscimol (0.1 g) into the deep SC/Me, but not the super SC, blocked the enhancement of startle by systemic SKF 82958 (1 mg/kg) but had no effect on baseline startle by itself. This effect was not produced by infusion of the D 1 antagonist SCH 23390(1 g) or the glutamate antagonist NBQX (0.1 g). Deposits of FluoroGold into the deep SC/Me, combined with immunohistochemistry for glutamic acid decarboxylase (GAD), confirmed a direct GABAergic input from the substantia nigra pars reticulata (SNr) to the deep SC/Me. These results suggest that GABA tone in the deep SC/Me modulates the expression of startle as well as the enhancement of startle by dopamine D 1 agonists. On the basis of these data and previous work, we have proposed a striatonigral-tectal-reticular neural pathway mediating the effects of dopamine D 1 agonists on startle. Key words: startle; superior colliculus; bicuculline; muscimol; SKF 82958; D 1 receptorThe acoustic startle reflex in rats is a rapid sensorimotor response elicited by a sudden and intense auditory stimulus (cf. Davis, 1984) and is mediated by a simple neural pathway in the brainstem consisting of cochlear root neurons (CRNs), neurons in the nucleus reticularis pontis caudalis (PnC), and motoneurons in the spinal cord (Lee et al., 1996). The amplitude of this short-latency response can be quantified easily and has been used extensively to study the neurocircuitry and neurochemistry involved in the modulation of reflex/motor behavior (cf. Davis, 1980). Along these lines, we have found that systemic administration of dopamine D 1 receptor agonists markedly increases the acoustic startle response (Meloni and Davis, 1999a). This effect is mediated in part by the activation of D 1 receptors in the substantia nigra pars reticulata (SNr; Meloni and Davis, 1997), a major output structure of the basal ganglia to premotor areas in the midbrain (Graybiel, 1984). Hence, we have been using D 1 agonist-induced enhancement of the acoustic startle response to study the neural mechanisms underlying dopaminergic control of motor behavior. In particular, we are interested in how SNr-dependent D 1 receptor agonist effects get transmitted to the primary acoustic startle pathway in the brainstem.In the present study we have focused on the deep layers of the superior c...

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Evidence for a gabaergic projection from the substantia nigra to the ventromedial thalamus and to the superior colliculus of the rat

Cited by 381 publications

References 30 publications

Regional neural activity within the substantia nigra during peri-ictal flurothyl generalized seizure stages

Regional neural activity within the substantia nigra during peri-ictal flurothyl generalized seizure stages

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

GABA in the Deep Layers of the Superior Colliculus/Mesencephalic Reticular Formation Mediates the Enhancement of Startle by the Dopamine D₁Receptor Agonist SKF 82958 in Rats

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Evidence for a gabaergic projection from the substantia nigra to the ventromedial thalamus and to the superior colliculus of the rat

Cited by 381 publications

References 30 publications

Regional neural activity within the substantia nigra during peri-ictal flurothyl generalized seizure stages

Regional neural activity within the substantia nigra during peri-ictal flurothyl generalized seizure stages

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

GABA in the Deep Layers of the Superior Colliculus/Mesencephalic Reticular Formation Mediates the Enhancement of Startle by the Dopamine D1Receptor Agonist SKF 82958 in Rats

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GABA in the Deep Layers of the Superior Colliculus/Mesencephalic Reticular Formation Mediates the Enhancement of Startle by the Dopamine D₁Receptor Agonist SKF 82958 in Rats