Posterior Midbrain-Induced Locomotion E. GARCIA-RILL, N, KINJO, Y. ATSUTA, Y. ISHIKAWA, M. WEBBER AND R. D. SKINNER
Received I6 October
1989
GARCIA-RILL, E., N. KINJO, Y. ATSUTA, Y. ISHIKAWA, M. WEBBBR AND R. I). SKINNER. Posrerior ~~r~jR-i~uce~ ~~c~~uti~~. BRAIN RES BULL 24(3) 499-508, 1990. -The purpose af thii study was to determine the nature of the neurochemical signals which impinge on the mesencephalic locomotor region fMk.Ri to produce locomotion in the rat. Injections of GABA antagonists into NADPH diaphorase-positive regions (PPN) were found to induce locomotion for short episodes (S-30 secf which were repeated for severat minutes (l-40 mitt). Such activity was blocked by injections of CABA and the GABA agonist, muscimoi. Locomotion was induced by injection of substance P (SP). which also produced short, repeated episodes of locomation. The more potent excitatory amino acid aganist, n-methyl-d-asp&c acid (NMDA), however. did produce dose-dependent, long-lasting (20 seed tin) locomotor episodes wbicb were repeated over prolonged periods at the higher concentrations used (2-24 minf. Additional injections of NMDA could drive stepping from a walk to a trot to a gallop. The effects of NMDA were block& by injections of the excitatory amino acid antagonist. ~nop~phonovaie~on~c acid (APV) (l-10 m.M). Preiiminary evidence suggests that carbachol 110-50 n&41. a cholineraic anon&. inhibits MDA-induced increases in muscle tone and epi.scdesof stepping. The effect of carbacbol was blacked by the chorineriic antagonist. a&opine. Locomotion
Me~nceph~~ic locomotor region
P~dunculo~ntine nucleus
NMDA
EtECTRfCAt stimulation of the me~ncephal~& Iocomotor region IMLR), a region of the posterior midbrain, long ago was reported to induce locomotion on a treadmill in decerebrate (33) and intact (38) cats. More recently, the MLR also was described in the rat (29, 35, 36). Localized injections of putative neu~~ansm~tte~ into the MLR have been found to induce locomotion in the cat (17). These studies established that neuron& elements and not axons of passage were responsible for the observed effects following MLR stimulation. They also established that the MLR in the cat was under GABAergic control since injections of GABA antagonists into the region were found to induce locomotion, while injections of GABA and GABA agonists were found to block electrical- and GABA an~gonist-induce l~omotion (17). hrjections of other putative ne~transmitte~ either were ineffective or partiahy effective. Later studies showed that substance P (SP) also induced locomotion when injected into the MLR of the cat (16). Preliminary studies have been carried out in the rat testing the effects of injections of putative ne~o~~smitters, their agonists and antagonists into the physiolo~~c~ly identified MLR (12,14). Studies using freely moving rats have shown that injections of GABA antagonists into the MLR increased locomotor activity (4). These studies confirmed our results on GABAergic control of stepping in the decerebrate rat and point to a functional roie for the PPNlMLR in locomotor control in the intact animal. A recent report describes the effects of injections of carbachol, a cholinergic agonist, into the ~duncu~o~ntine nucleus (PPN) as decreasing spontaneous locomotor activity in the intact rat (5). This suggests that the choiinergic input to the PPN. which pa&y may arise from recutmnt collaterals, the contralateral PPN an&or the nearby chofinergic laterodorsal tegmental nucleus (10,32), may have a net inhibitory effect on locomotion. Work in the guinea pig slice preparation also showed cholinergic PPN neurons to be inhibited by cholinergic agents (24).
Previous ftndings in the cat had shown that injections of ghrtamic acid, while not inducing locomotion oufright, did produce an increase in postural tone and lowered the threshold for electrically induced locomotion (17). The present studies made use of excitatory amino acid reuptake inhibitors and potent receptor agonists and antagonists to demonstrate the presence of an excitatory amino acid input to the PPNIMLR. The locomotion induced by these agents proved to be the most consistent to date, Since the effects of injections of excitatory amino acid agonists and antagonists and of cholinergic agents into the PPN/MLR of the cat had not previously been described, the results obtained in the rat were confirmed in a short series of experiments in the cat. While these may appear to be straightforward experiments, there is considerable variability in the ~~~~zatjon of the MLR in both the cat and the rat. Part of the variation across laboratories appears to arise from differences in protocol such as, I) Lack of strict adherence to low threshold (
Received I6 October
1989
GARCIA-RILL, E., N. KINJO, Y. ATSUTA, Y. ISHIKAWA, M. WEBBBR AND R. I). SKINNER. Posrerior ~~r~jR-i~uce~ ~~c~~uti~~. BRAIN RES BULL 24(3) 499-508, 1990. -The purpose af thii study was to determine the nature of the neurochemical signals which impinge on the mesencephalic locomotor region fMk.Ri to produce locomotion in the rat. Injections of GABA antagonists into NADPH diaphorase-positive regions (PPN) were found to induce locomotion for short episodes (S-30 secf which were repeated for severat minutes (l-40 mitt). Such activity was blocked by injections of CABA and the GABA agonist, muscimoi. Locomotion was induced by injection of substance P (SP). which also produced short, repeated episodes of locomation. The more potent excitatory amino acid aganist, n-methyl-d-asp&c acid (NMDA), however. did produce dose-dependent, long-lasting (20 seed tin) locomotor episodes wbicb were repeated over prolonged periods at the higher concentrations used (2-24 minf. Additional injections of NMDA could drive stepping from a walk to a trot to a gallop. The effects of NMDA were block& by injections of the excitatory amino acid antagonist. ~nop~phonovaie~on~c acid (APV) (l-10 m.M). Preiiminary evidence suggests that carbachol 110-50 n&41. a cholineraic anon&. inhibits MDA-induced increases in muscle tone and epi.scdesof stepping. The effect of carbacbol was blacked by the chorineriic antagonist. a&opine. Locomotion
Me~nceph~~ic locomotor region
P~dunculo~ntine nucleus
NMDA
EtECTRfCAt stimulation of the me~ncephal~& Iocomotor region IMLR), a region of the posterior midbrain, long ago was reported to induce locomotion on a treadmill in decerebrate (33) and intact (38) cats. More recently, the MLR also was described in the rat (29, 35, 36). Localized injections of putative neu~~ansm~tte~ into the MLR have been found to induce locomotion in the cat (17). These studies established that neuron& elements and not axons of passage were responsible for the observed effects following MLR stimulation. They also established that the MLR in the cat was under GABAergic control since injections of GABA antagonists into the region were found to induce locomotion, while injections of GABA and GABA agonists were found to block electrical- and GABA an~gonist-induce l~omotion (17). hrjections of other putative ne~transmitte~ either were ineffective or partiahy effective. Later studies showed that substance P (SP) also induced locomotion when injected into the MLR of the cat (16). Preliminary studies have been carried out in the rat testing the effects of injections of putative ne~o~~smitters, their agonists and antagonists into the physiolo~~c~ly identified MLR (12,14). Studies using freely moving rats have shown that injections of GABA antagonists into the MLR increased locomotor activity (4). These studies confirmed our results on GABAergic control of stepping in the decerebrate rat and point to a functional roie for the PPNlMLR in locomotor control in the intact animal. A recent report describes the effects of injections of carbachol, a cholinergic agonist, into the ~duncu~o~ntine nucleus (PPN) as decreasing spontaneous locomotor activity in the intact rat (5). This suggests that the choiinergic input to the PPN. which pa&y may arise from recutmnt collaterals, the contralateral PPN an&or the nearby chofinergic laterodorsal tegmental nucleus (10,32), may have a net inhibitory effect on locomotion. Work in the guinea pig slice preparation also showed cholinergic PPN neurons to be inhibited by cholinergic agents (24).
Previous ftndings in the cat had shown that injections of ghrtamic acid, while not inducing locomotion oufright, did produce an increase in postural tone and lowered the threshold for electrically induced locomotion (17). The present studies made use of excitatory amino acid reuptake inhibitors and potent receptor agonists and antagonists to demonstrate the presence of an excitatory amino acid input to the PPNIMLR. The locomotion induced by these agents proved to be the most consistent to date, Since the effects of injections of excitatory amino acid agonists and antagonists and of cholinergic agents into the PPN/MLR of the cat had not previously been described, the results obtained in the rat were confirmed in a short series of experiments in the cat. While these may appear to be straightforward experiments, there is considerable variability in the ~~~~zatjon of the MLR in both the cat and the rat. Part of the variation across laboratories appears to arise from differences in protocol such as, I) Lack of strict adherence to low threshold (
