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Posterior midbrain-induced locomotion
E Garcia-Rill1, N Kinjo, Y Atsuta
1Department of Anatomy, University of Arkansas for Medical Sciences, Little Rock 72205.
Abstract:
The purpose of this study was to determine the nature of the neurochemical signals which impinge on the mesencephalic locomotor region (MLR) to produce locomotion in the rat. Injections of GABA antagonists into NADPH diaphorase-positive regions (PPN) were found to induce locomotion for short episodes (5-30 sec) which were repeated for several minutes (1-40 min). Such activity was blocked by injections of GABA and the GABA agonist, muscimol. Locomotion was induced by injection of substance P (SP), which also produced short, repeated episodes of locomotion. The more potent excitatory amino acid agonist, n-methyl-d-aspartic acid (NMDA), however, did produce dose-dependent, long-lasting (20 sec-5 min) locomotor episodes which were repeated over prolonged periods at the higher concentrations used (2-24 min). Additional injections of NMDA could drive stepping from a walk to a trot to a gallop. The effects of NMDA were blocked by injections of the excitatory amino acid antagonist, aminophosphonovalerionic acid (APV) (1-10 mM). Preliminary evidence suggests that carbachol (10-50 mM), a cholinergic agonist, inhibits NMDA-induced increases in muscle tone and episodes of stepping. The effect of carbachol was blocked by the cholinergic antagonist, atropine.
Insights
Neurochemical signals in the rat
Area of Science:
- Neuroscience
- Motor Control
- Neuropharmacology
Background:
- Locomotion is a complex behavior controlled by the central nervous system.
- The mesencephalic locomotor region (MLR) plays a crucial role in initiating and maintaining locomotion.
- Understanding the neurochemical basis of MLR activation is essential for deciphering motor control.
Purpose of the Study:
- To investigate the specific neurochemical signals that trigger locomotion when acting on the mesencephalic locomotor region (MLR).
- To differentiate the roles of inhibitory and excitatory neurotransmission in MLR-driven locomotion.
Main Methods:
- Injections of various neurochemicals (GABA antagonists, GABA, muscimol, substance P, NMDA, carbachol, atropine) into specific brain regions of rats.
- Observation and quantification of locomotor activity (duration, frequency, intensity).
- Assessment of muscle tone changes.
Main Results:
- GABA antagonists in the NADPH diaphorase-positive regions (PPN) induced short, repeatable locomotion episodes.
- Substance P also initiated brief, repeated locomotion.
- N-methyl-d-aspartic acid (NMDA) produced dose-dependent, prolonged locomotion, including varied gaits (walk, trot, gallop).
- NMDA-induced locomotion was blocked by APV, an NMDA antagonist.
- Cholinergic agonist carbachol inhibited NMDA-driven locomotion and muscle tone, an effect reversed by atropine.
Conclusions:
- Both GABAergic and excitatory amino acid systems within the PPN are involved in MLR-mediated locomotion.
- NMDA receptor activation is a potent driver of sustained locomotion, capable of modulating gait.
- Cholinergic pathways appear to modulate, rather than initiate, locomotion driven by NMDA.
- These findings elucidate key neurochemical pathways controlling locomotion initiation and modulation.