Response of dopamine neurons in substantia nigra to muscimol

Macneil, Donald A.; Gower, Marie; I, Szymańska

doi:10.1016/0006-8993(78)90713-8

Cited by 64 publications

(18 citation statements)

References 9 publications

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“…PFC terminals, however, form direct contacts with some VTA GABA neurons, raising the possibility that part of PFC influence on DA neurons is indirectly mediated through these inhibitory cells. Consistent with this possibility, the GABA A agonist muscimol, which has been shown to preferentially inhibit GABA neurons in the VTA and the substantia nigra (MacNeil et al, 1978;Walters and Lakoski, 1978;Grace and Bunney, 1979;Tepper et al, 1995), inhibits the SO in DA neurons (Shi et al, 2004). Also consistent with this possibility, a subset of VTA non-DA neurons was found to fire in synchrony with the active, up states of PFC cells.…”

Section: Evidence For An Inhibitory Influence Of the Pfc On Da Neuronsmentioning

confidence: 61%

Functional Coupling between the Prefrontal Cortex and Dopamine Neurons in the Ventral Tegmental Area

Gao

Liu²,

Shen³

et al. 2007

J. Neurosci.

114

120

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Stimulation of the prefrontal cortex (PFC) has been shown to have an excitatory influence on dopamine (DA) neurons. We report here that, under nonstimulated conditions, the activity of DA neurons in the ventral tegmental area (VTA) also covaries, on a subsecond timescale, with the activity of PFC cells. Thus, in 67% of VTA DA neurons recorded in chloral hydrate-anesthetized rats, the firing of the cell displayed a slow oscillation (SO) that was highly coherent with the activity of PFC neurons. The SO was suppressed by transections immediately caudal to the PFC or by intra-PFC infusion of tetrodotoxin, suggesting that it depends on inputs derived from the PFC. Unexpectedly, the SO in most VTA DA neurons was reversed in phase relative to PFC cell activity, suggesting that at least part of PFC information is transferred to DA neurons indirectly through inhibitory relay neurons. These results, together with those reported previously, suggest that the PFC can act through multiple pathways to exert both excitatory and inhibitory influences on DA neurons. The observed functional coupling between DA and PFC neurons further suggests that these pathways not only allow a bidirectional control of DA neurons by the PFC, but also enable action potential-dependent DA release to be coordinated, on a subsecond timescale, with glutamate release from PFC terminals. Further understanding of this coordinated activity may provide important new insights into brain functions and disorders thought to involve both VTA DA and PFC neurons.

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Section: Evidence For An Inhibitory Influence Of the Pfc On Da Neuronsmentioning

confidence: 61%

Functional Coupling between the Prefrontal Cortex and Dopamine Neurons in the Ventral Tegmental Area

Gao

Liu²,

Shen³

et al. 2007

J. Neurosci.

114

120

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“…We suggest that SN LFPs represent mainly the synaptic activities in SN non-DA neurons because the firing of most DA neurons had a nearly antiphase relation with SN LFP. Furthermore, muscimol, which preferentially inhibits SN non-DA neurons (MacNeil et al, 1978;Walters and Lakoski, 1978;Grace and Bunney, 1979;Waszczak and Walters, 1980), consistently suppressed the SO in SN LFP. The finding that muscimol also inhibits the SO in DA neurons (Gao et al, 2007 and present study) further supports the suggestion that the SO is relayed through SN/VTA non-DA neurons to DA cells.…”

Section: Discussionmentioning

confidence: 81%

“…The GABA A agonist muscimol is known to preferentially inhibit VTA/SN non-DA neurons when given systemically (MacNeil et al, 1978;Walters and Lakoski, 1978;Grace and Bunney, 1979;Waszczak and Walters, 1980). If SN LFPs represent synaptic activities in non-DA neurons, muscimol would differ from L-DOPA and apomorphine, inhibiting LFP SO in the SN.…”

Section: Effects Of L-dopa On Dopamine Neurons 535mentioning

confidence: 99%

“…5). This increase is believed to be secondary to the inhibition of non-DA neurons by muscimol (MacNeil et al, 1978;Walters and Lakoski, 1978;Grace and Bunney, 1979;Waszczak and Walters, 1980).…”

Section: Effects Of L-dopa On Dopamine Neurons 535mentioning

confidence: 99%

“…Previous studies in the ventral tegmental area (VTA) suggest that the SO is transferred from the forebrain to DA neurons through VTA GABA cells and LFPs in the VTA reflect the synchronized synaptic activities in these non-DA neurons (Gao et al, 2007). To test whether the SO in SN DA neurons is generated by a similar mechanism, we studied the effect of muscimol, a GABA A agonist previously shown to preferentially inhibit VTA/SN non-DA neurons (MacNeil et al, 1978;Walters and Lakoski, 1978;Grace and Bunney, 1979;Waszczak and Walters, 1980). We hypothesized that muscimol, by inhibiting SN non-DA cells, inhibits the SO in both DA cell firing and SN LFPs, whereas L-DOPA produces its effect primarily through DA autoreceptors and therefore has little or no effect on SN LFPs.…”

Section: Introductionmentioning

confidence: 99%

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Effects of l-DOPA on Nigral Dopamine Neurons and Local Field Potential: Comparison with Apomorphine and Muscimol

Xu¹,

Karain²,

Brantley³

et al. 2011

J Pharmacol Exp Ther

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L-DOPA is more effective than direct dopamine (DA) agonists in relieving the motor deficits in Parkinson's disease. Using in vivo recording, we compared the effect of L-DOPA and the direct DA agonist apomorphine on DA neurons in rat substantia nigra (SN). L-DOPA (50 -100 mg/kg i.v.) decreased the firing rate as well as the variability and slow oscillation (SO) of firing. All effects were blocked by raclopride and mimicked by quinpirole, suggesting that they are mediated through D2-like receptors. Autoreceptor-selective doses of apomorphine (5-20 g/kg i.v.) also inhibited all three parameters. The magnitude of the inhibition, however, was significantly greater than that induced by L-DOPA. Neither L-DOPA nor apomorphine had a consistent effect on SN local field potentials (LFPs). The GABA agonist muscimol, known to preferentially inhibit SN non-DA neurons, consistently inhibited the SO in both DA cell firing and LFPs. These results suggest that SN LFPs mainly reflect the synaptic potentials in non-DA neurons, and L-DOPA and apomorphine, unlike muscimol, affect DA neurons primarily through DA autoreceptors. DA autoreceptor activation is known to hyperpolarize DA cells by increasing the membrane conductance to K ϩ . This increase in membrane conductance would shunt synaptic input to DA neurons, thereby decreasing the variability and SO in DA cell firing. The low potency of L-DOPA to inhibit DA cell firing and reduce their responses to synaptic input may partially account for its superior therapeutic efficacy in Parkinson's disease compared with apomorphine and other direct DA agonists.

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Inhibition of dopamine re-uptake: Significance for nigral dopamine neuron activity

Engberg

Elverfors

Jonason

et al. 1997

Synapse

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In the present study the effect of inhibition of the re-uptake of dopamine (DA) was analysed with respect to DA release and to the firing pattern of DA neurons in the substantia nigra (SN). Intravenous administration of GBR 12909 (0.5-8 mg/kg), a specific and potent inhibitor of DA re-uptake, was found to dose-dependently increase the DA concentration both in the SN and in the striatum, as measured by microdialysis. However, the drug failed to significantly affect the firing rate of the nigral DA neurons. In contrast, GBR 12909 dose-dependently induced a regularisation of the firing pattern, concomitant with a reduction in burst activity. An acute hemisection of the brain, which by itself produced a slight regularisation of the firing pattern of the nigral DA neurons without changing the firing rate of the ability of the DA neurons to fire in bursts, was found to prevent the regulatory action of GBR 12909. Pretreatment with the selective GABAB-receptor antagonist CGP 35348 (200 mg/kg, i.v., 5 min) did not significantly affect the firing rate, the regularity of the DA neurons, or their ability to fire in bursts. However, CGP 35348 markedly antagonised the ability of GBR 12909 to induce pacemaker-like firing or a decrease in burst activity of the nigral DA neurons. The results of the present study suggest that a striatonigral feedback projection may serve to control the activity of nigral DA neurons not primarily by regulating the firing rate, but, preferably, by modulating the firing pattern of the neurons. In this regard, activation of somatodendritic GABAB-receptors may form the final link in this feedback inhibitory control system.

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Response of dopamine neurons in substantia nigra to muscimol

Cited by 64 publications

References 9 publications

Functional Coupling between the Prefrontal Cortex and Dopamine Neurons in the Ventral Tegmental Area

Functional Coupling between the Prefrontal Cortex and Dopamine Neurons in the Ventral Tegmental Area

Effects of l-DOPA on Nigral Dopamine Neurons and Local Field Potential: Comparison with Apomorphine and Muscimol

Inhibition of dopamine re-uptake: Significance for nigral dopamine neuron activity

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