Pharmacologically defined M1 and M2 muscarinic cholinergic binding sites in the cat's substantia nigra: development and maturity

Nastuk, Mary A.; Graybiel, Ann M.

doi:10.1016/0165-3806(91)90108-u

Cited by 27 publications

(5 citation statements)

References 55 publications

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“…Both [3H]acetylcholine and [3H]nicotine display a high binding affinity in the substantia nigra of rats (Clarke and Pert, 1985;Clarke et al, 1985a). Cholinergic receptors of both nicotinic and muscarinic types are known to be present at substantia nigra levels, some being preferentially located on dopaminergic neurons of the SNc (Rotter et al, 1979;Clarke and Pert, 1985;Nastuk and Graybiel., 1991). An increase in the activity of SNc cells is observed after either electrical stimulation of the PPN neurons or exogenous application of acetylcholine and nicotine (Lichensteiger et al, 1976(Lichensteiger et al, , 1982Scarnati et al, 1984;Clarke et al, 198510,1987;Niijima and Yoshida, 1988).…”

Section: Discussionmentioning

confidence: 99%

Pedunculopontine nucleus in the squirrel monkey: Cholinergic and glutamatergic projections to the substantia nigra

Lavoie

Parent

1994

J of Comparative Neurology

210

102

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The distribution and chemospecificity of the pedunculonigral neurons have been studied in squirrel monkeys (Saimiri sciureus) with cholera toxin subunit B (CTb) and fluorogold (FG) as retrograde tracers combined with immunohistochemistry for choline acetyltransferase (ChAT), glutamate, and the calcium binding protein calbindin D-28k. The injection of either CTb or FG into the substantia nigra produces prominent retrograde cell labeling in the mesopontine tegmentum. Labeled neurons are particularly numerous at the level of the decussation of the superior cerebellar peduncle, where they abound principally in the pars dissipata of the pedunculopontine nucleus (PPN). A significant proportion of retrogradely labeled neurons in the PPN display ChAT immunoreactivity. Within the entire PPN, approximately 25% of the retrogradely labeled neurons express ChAT immunoreactivity, but proportions of doubly labeled neurons are about 35%, 25%, and 15% in the rostral, middle, and caudal thirds of the PPN, respectively. These doubly labeled neurons are scattered among numerous retrogradely labeled neurons that are ChAT-negative and whose number increases along the rostrocaudal extent of the PPN. Several retrogradely labeled neurons in the PPN display glutamate immunoreactivity, but very few express calbindin. This study provides the first direct evidence for the involvement of cholinergic and glutamatergic neurons in the pedunculonigral projection in primates. Furthermore, the fact that some neurons of the PPN display both ChAT and glutamate immunoreactivity indicates that single neurons in the mesopontine tegmentum may exert a two-fold effect upon dopaminergic neurons of the substantia nigra. This dual cholinergic and glutamatergic pedunculonigral projection may play a crucial role in the functional organization of primate basal ganglia.

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Section: Discussionmentioning

confidence: 99%

Pedunculopontine nucleus in the squirrel monkey: Cholinergic and glutamatergic projections to the substantia nigra

Lavoie

Parent

1994

J of Comparative Neurology

210

102

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“…Anatomical observations show that the mesencephalic DA nuclei receive a cholinergic innervation from the pedunculopontine tegmental nuclei (PPN) and the laterodorsal tegmental nucleus (Woolf and Butcher, 1986;Spencer, 1987, 1988;Gould et al, 1989;Tokuno et al, 1988, but see Lee et al, 1988). High densities of muscarinic (Nastuk and Graybiel, 1991) and nicotinic receptors have been observed in the SNpc (see above), with a pattern resembling that of acetylcholinesterase (AChE) (Paxinos et al, 1980). There is also functional evidence for cholinergic innervation (Clarke et al, 1987).…”

Section: The Cholinergic Circuits In the Mesencephalic Dopaminergic Nmentioning

confidence: 99%

Ultrastructural Localization of the α4-Subunit of the Neuronal Acetylcholine Nicotinic Receptor in the Rat Substantia Nigra

et al. 1999

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The distribution of the alpha4-subunit of the neuronal nicotinic acetylcholine receptor (nAChR) in the rat brain was examined at light and electron microscopy levels using immunohistochemical staining. In the present study we demonstrate the specificity, in both tissue homogenates and brain sections, of a polyclonal antibody raised against the rat nAChR alpha4-subunit. The characterization of this antibody involved: (1) Western blot analysis of rat brain homogenates and membrane extracts from cells previously transfected with diverse combinations of neuronal nAChR subunits, and (2) immunohistochemistry using transfected cells and rat brain tissue. At the light microscope level, the alpha4-subunit-like-immunoreactivity (LI) was widely distributed in the rat brain and matched the distribution of the alpha4-subunit transcripts observed previously by in situ hybridization. Strong immunohistochemical labeling was detected in the mesencephalic dopaminergic nuclei. The nAChRs in this region are thought to be responsible for the modulation of dopaminergic transmission. The neurotransmitter identity of alpha4-immunolabeled neurons in the substantia nigra pars compacta (SNpc) and the ventral tegmental area was thus assessed by investigating the possible colocalization of the nAChR alpha4-subunit with tyrosine hydroxylase using confocal microscopy. The double labeling experiments unambiguously indicated that the alpha4-subunit-LI is present in dopaminergic neurons. At the electron microscope level, the neurons in the SNpc exhibited alpha4-subunit-LI in association with a minority of postsynaptic densities, suggesting that the alpha4-subunit may be a component of functional nAChRs mediating synaptic transmission between midbrain cholinergic neurons and mesencephalic dopaminergic neurons.

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“…Neurons in the SNr express nicotinic and muscarinic ACh receptors (nAChRs and mAChRs) (Nastuk and Graybiel, 1991; Klink et al, 2001; Wooltorton et al, 2003; Michel et al, 2004; Poisik et al, 2008). Locally applied ACh causes excitation of SNr GABA neurons in vivo (Collingridge and Davies, 1981; Pinnock and Dray, 1982).…”

Section: Synaptic Inputs To Snr Gaba Projection Neurons and Their mentioning

confidence: 99%

Intrinsic and integrative properties of substantia nigra pars reticulata neurons

Zhou

Lee

2011

Neuroscience

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The GABA projection neurons of the substantia nigra pars reticulata (SNr) are output neurons for the basal ganglia and thus critical for movement control. Their most striking neurophysiological feature is sustained, spontaneous high frequency spike firing. A fundamental question is: what are the key ion channels supporting the remarkable firing capability in these neurons? Recent studies indicate that these neurons express tonically active TRPC3 channels that conduct a Na-dependent inward current even at hyperpolarized membrane potentials. When the membrane potential reaches −60 mV, a voltage-gated persistent sodium current (INaP) starts to activate, further depolarizing the membrane potential. At or slightly below −50 mV, the large transient voltage-activated sodium current (INaT) starts to activate and eventually triggers the rapid rising phase of action potentials. SNr GABA neurons have a higher density of (INaT), contributing to the faster rise and larger amplitude of action potentials, compared with the slow-spiking dopamine neurons. INaT also recovers from inactivation more quickly in SNr GABA neurons than in nigral dopamine neurons. In SNr GABA neurons, the rising phase of the action potential triggers the activation of high-threshold, inactivation-resistant Kv3-like channels that can rapidly repolarize the membrane. These intrinsic ion channels provide SNr GABA neurons with the ability to fire spontaneous and sustained high frequency spikes. Additionally, robust GABA inputs from direct pathway medium spiny neurons in the striatum and GABA neurons in the globus pallidus may inhibit and silence SNr GABA neurons, whereas glutamate synaptic input from the subthalamic nucleus may induce burst firing in SNr GABA neurons. Thus, afferent GABA and glutamate synaptic inputs sculpt the tonic high frequency firing of SNr GABA neurons and the consequent inhibition of their targets into an integrated motor control signal that is further fine-tuned by neuromodulators including dopamine, serotonin, endocannabinoids, and H2O2.

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Pharmacologically defined M1 and M2 muscarinic cholinergic binding sites in the cat's substantia nigra: development and maturity

Cited by 27 publications

References 55 publications

Pedunculopontine nucleus in the squirrel monkey: Cholinergic and glutamatergic projections to the substantia nigra

Pedunculopontine nucleus in the squirrel monkey: Cholinergic and glutamatergic projections to the substantia nigra

Ultrastructural Localization of the α4-Subunit of the Neuronal Acetylcholine Nicotinic Receptor in the Rat Substantia Nigra

Intrinsic and integrative properties of substantia nigra pars reticulata neurons

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