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Substantia nigra control of basal ganglia nuclei
No full textAbstract. The substantia nigra, located in the ventral mesencephalon,
is one of the five nuclei that constitute the basal
ganglia circuit, which controls voluntary movements.
It is divided into the pars compacta and the pars reticulata,
which mainly contain dopaminergic and GABAergic
cells respectively. Here we overview the electrophysiological
properties of these substantia nigra neurons in the pars
compacta and reticulata, together with their synaptic connections,
and discuss the functional effects of dopaminergic
and GABAergic inputs within the basal ganglia. We also
examine the phenomenon that when a deficiency of dopamine
(DA) occurs (e.g. in Parkinson’s disease), there is an
aberrant synaptic plasticity in the basal ganglia.
Moreover, we point out that the appearance of an altered
pattern of neuronal firing (beta-oscillations) and synchrony
among neurons in the subthalamic nucleus, the internal
globus pallidus, and the substantia nigra pars reticulata has
been related to motor symptoms and possibly, persistent
degeneration of DA-containing neurons.
Finally, we believe that, based on pathophysiological
data, new and significant targets for therapeutic intervention
can be identified and tested
Activation of quisqualate metabotropic receptors reduces glutamate and GABA-mediated synaptic potentials in the rat striatum.
No full textUn caso di ictus cerebrale causato da una dissecazione spontanea della carotide interna a rapida risoluzione. [A case of cerebral stroke caused by a spontaneous dissection of the internal carotid with rapid resolution]
No full textPhysiology and pharmacology of dopamine D2-receptors: their implications in dopamine-substitute therapy for Parkinson's disease.
No full textSynaptic and intrinsic control of membrane excitability of neostriatal neurons. II. An in vitro analysis.
No full textGroup I mGluRs coupled to G proteins are regulated by tyrosine kinase in dopamine neurons of the rat midbrain
No full textGroup I mGluRs coupled to G proteins are
regulated by tyrosine kinase in dopamine neurons of the rat midbrain.
J Neurophysiol 85: 2490–2497, 2001. Metabotropic glutamate receptors
(mGluRs) modulate neuronal function via different transduction
mechanisms that are either dependent or independent on G-protein
function. Here we investigated, using whole cell patch-clamp recordings
in combination with fluorimetric measurements of intracellular
calcium concentration ([Ca21]i), the metabolic pathways involved in
the responses induced by group I mGluRs in dopamine neurons of the
rat midbrain. The inward current and the [Ca21]i increase caused by
the group I mGluR agonist (S)-3,5-dihydroxyphenylglycine (DHPG,
100 mM) were permanently activated and subsequently abolished in
cells loaded with the nonhydrolizable GTP-analogue GTP-g-S (600
mM). In addition, when GDP-b-S (600 mM) was dialyzed into the
cells to produce the blockade of the G proteins, the DHPG-dependent
responses were reduced. When the tissue was bathed with the phospholipase
C inhibitor 1-[6[[(17b)-3-methoxyestra-1,3,5(10)-trien-17-
yl]amino]exyl]-1H-pyrrole-2,5-dione (10 mM), the DHPG-induced
calcium transients slightly diminished but the associated inward currents
were not affected. Interestingly, a substantial depression of the
DHPG-induced inward current and transient increase of [Ca21]i was
caused by the protein tyrosine kinase inhibitors tyrphostin B52 (40
mM) and 49,5,7-trihydroxyisoflavone (genistein; 40 mM), whereas
genistein’s inactive analogue 49,5,7-trihydroxyisoflavone-7-glucoside
(40 mM) was ineffective. The blockade of the Src family of tyrosine
kinase by 4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]-
pyrimidine (20 mM), mitogen-activated protein kinase by 29-amino-39
methoxyflavone (50 mM), and protein kinase C by staurosporine (1
mM) had no effect on the cellular responses caused by DHPG. The
mGluR5-selective antagonist 2-methyl-6-(phenylethynyl)-pyridine
(10–100 mM) did not affect the actions of DHPG. Thus our results
indicate that the responses, mainly mediated by mGluRs1 in dopamine
neurons, are activated by intracellular mechanisms coupled to G
proteins and regulated by tyrosine kinases
Responses of rat mesencephalic dopaminergic neurons to a prolonged period of oxygen deprivation.
No full textHeterogeneity of metabotropic glutamate receptors in the striatum: electrophysiological evidence.
No full textGroup I metabotropic glutamate receptors mediate an inward current in rat substantia nigra dopamine neurons that is independent from calcium mobilization
No full textMetabotropic glutamate receptors modulate neuronal excitabil- ity via a multitude of mechanisms, and they have been implicated in the pathogenesis of neurodegenerative processes. Here we investi- gated the responses mediated by group I metabotropic glutamate receptors (mGluRs) in dopamine neurons of the rat substantia nigra pars compacta, using whole cell patch-clamp recordings in combina- tion with microfluorometric measurements of [Ca2 ]i and [Na ]i. The selective group I mGluR agonist (S)-3,5-dihydroxyphenylglycine (3,5-DHPG) was bath-applied (20 M, 30 s to 2 min) or applied locally by means of short-lasting (2–4 s) pressure pulses, delivered through an agonist-containing pipette positioned close to the cell body of the neuron. 3,5-DHPG evoked an inward current characterized by a transient and a sustained component, the latter of which was un- covered only with long-lasting agonist applications. The fast compo- nent coincided with a transient elevation of [Ca2 ]i, whereas the total current was associated with a rise in [Na ]i. These responses were not affected either by the superfusion of ionotropic excitatory amino acid antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and D-2-amino-5-phosphono-pentanoic acid (D-APV), nor by the sodium channel blocker tetrodotoxin (TTX). (S)- -methyl-4-carboxyphenyl- glycine (S-MCPG) and the more selective mGluR1 antagonist 7(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate (CPCCOEt) de- pressed both 3,5-DHPG–induced inward current components and, al- though less effectively, the associated [Ca2 ]i elevations. On repeated agonist applications the inward current and the calcium transients both desensitized. The time constant of recovery from desensitization differed significantly between these two responses, being 67.4 4.4 s for the inward current and 28.6 2.7 s for the calcium response. Bathing the tissue in a calcium-free/EGTA medium or adding thapsigargin (1 M) to the extracellular medium prevented the generation of the [Ca2 ]i tran- sient, but did not prevent the activation of the inward current. These electrophysiological and fluorometric results show that the 3,5-DHPG– induced inward current and the [Ca2 ]i elevations are mediated by independent pathways downstream the activation of mGluR1
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