The rat ventromedial thalamic nucleus and motor control: role of N-methyl-D-aspartate-mediated excitation, GABAergic inhibition, and muscarinic transmission.
The rat ventromedial thalamic nucleus (VM) is a point of convergence of several pathways that are supposed to be involved in motor control. Cortical fibers terminating within this nucleus use an excitatory amino acid, possibly L-glutamate, as their transmitter. Excitatory amino acids are known to interact with N-methyl-D-aspartate (NMDA), kainate, and quisqualate receptors, the presence of which has been demonstrated within the thalamus, gamma-Amino-butyrate (GABA) has been identified as the transmitter of the basal ganglia afferents to the VM, whereas cerebellar afferents to the VM are supposed to release ACh acting on muscarinic receptors. The present study investigates the behavioral and motor consequences of local injections of drugs into the VM, which specifically interact with NMDA, GABA, and muscarine receptors. Both the NMDA antagonist (-)2-amino-7-phosphonoheptanoate [(-)AP7], and the GABA agonist muscimol, but not the muscarinic antagonist scopolamine, induced catalepsy and limb rigidity. Both the (-)AP7- and muscimol-induced catalepsy were antagonized by coadministration of NMDA and the GABA antagonist bicuculline. The (-)AP7-induced catalepsy was characterized as an akinetic-rigid syndrome, in which the ability to induce a phasic activation of a set of muscles is lost and replaced by exaggerated tonic muscular responses. NMDA, bicuculline, and the muscarinic agonist bethanechol induced an increase in locomotor activity. The present study provides evidence that an imbalance between NMDA-mediated excitation and GABAergic inhibition within the rat VM leads to disturbances of motility, whereas muscarinic transmission within this nucleus appears to be of minor importance.
Klockgether
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T
Schwarz
M
M
Turski
L
L
Sontag
K H
KH
D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D004576:Electromyography; D008124:Locomotion / Q000187:drug effects; D008297:Male; D009068:Movement / Q000187:drug effects*; D009118:Muscimol / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D016202:N-Methylaspartate; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology; D018377:Neurotransmitter Agents / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D009435:Synaptic Transmission / Q000187:drug effects*; D013787:Thalamic Nuclei / Q000187:drug effects* / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D018377:Neurotransmitter Agents; D009118:Muscimol; D001224:Aspartic Acid; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate