Abstract
The possible role of GABAergic mechanisms in the control of the basal ganglia output structures, the globus pallidus (GP) and the entopeduncular nucleus (EP), was studied in cats performing a conditioned flexion movement triggered by an auditory stimulus. The effects of discrete unilateral microinjections of low doses of the GABAA receptor agonist (muscimol 5–100 ng/ 0.5 μl) and antagonist (bicuculline methiodide 25–150 ng/0.5 μl) in the GP and the EP were tested on the motor performance of eight animals trained to release a lever in a simple reaction time (RT) schedule after an auditory stimulus. Control injections in neighboring structures did not induce any effect except with five- to tenfold higher doses in the closest injection sites. The dose of 20 ng muscimol injected into the ventral and medial part of the GP produced an arrest of the performance after a few unsuccessful trials (over the RT reinforcement limit of 500 ms), while muscimol injected in sites located in the lateral GP resulted in a dose-dependent lengthening in RTs, with a concomitant increase in the force change latency. In most of the subjects, the force exerted on the lever was higher after muscimol than after vehicle injection. Force change velocity was then significantly increased. In contrast, muscimol injected in the ventral and rostral region of the EP produced a decrease in RTs or a complete cessation of responding after a high number of anticipatory responses (release of the lever before the trigger stimulus). No significant changes in the force change latency could be observed while there was a non-significant tendency for the force levels to be lowered. Bicuculline injections in the EP were found to increase RTs with a concomitant increase in force change latency and a slowness of velocity, while no significant effect was observed following injections in the GP. These results suggest that a balance between GABAergic activity in the two output nuclei of the basal ganglia, the GP and the EP, is crucial for the correct initiation and execution of the conditioned motor task.
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References
Alamy M, Trouche E, Nieoullon A, Legallet E (1994) Globus pallidus and motor initiation: the bilateral effects of unilateral quisqualic acid induced-lesion on reaction times in monkeys. Exp Brain Res 99:247–258
Albin RL, Young AB, Penney JB (1989) The functional anatomy of basal ganglia disorders. Trends Neurosci 12:366–375
Alexander GE, DeLong MR, Strick PL (1986) Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annu Rev Neurosci 9:357–381
Amalric M, Koob GF (1987) Depletion of dopamine in the caudate nucleus but not nucleus accumbens impairs reaction time performance in rats. J Neurosci 7:2129–2134
Amalric M, Koob GF (1989) Dorsal pallidum as a functional motor output of the corpus striatum. Brain Res 483:389–394
Amalric M, Schmied A, Farin D, Dormont JF (1989) Motor impairments produced by modulation of GABAergic afferences of the pallidum in the cat. Soc Neurosci Abstr 15:912
Anderson ME, Horak FB (1985) Influence of the globus pallidus on arm movements in monkeys. III. Timing of movement-related information. J Neurophysiol 54:433–448
Anderson ME, Turner RS (1991) A quantitative analysis of pallidal discharge during targeted reaching movement in the monkey. Exp Brain Res 86:623–632
Beaubaton D, Trouche E, Amato G, Legallet E (1981) Perturbations du déclenchement et de l'exécution d'un mouvement visuellement guidé chez le babouin au cours du refroidissement ou après lésion du segment interne du globus pallidus. J Physiol (Paris) 77:107–118
Beckstead RM, Cruz CJ (1986) Striatal axons to the globus pallidus, entopeduncular nucleus and substantia nigra corne mainly from separate cell populations in cat. Neuroscience 19:147–158
Bénita M, Condé H, Dormont JF, Schmied A (1979a) Effects of ventrolateral thalamic nucleus cooling on initiation of forelimb ballistic flexion movements by conditioned cats. Exp Brain Res 34:435–452
Bénita M, Condé H, Dormont JF, Schmied A (1979b) Effects of caudate nucleus cooling on the performance of conditioned movements in cats. Neurosci Lett 14:25–30
Brotchie P, Iansek R, Horne MK (1991a) Motor function of the monkey globus pallidus. 1. Neuronal discharge and parameters of movement. Brain 114:1667–1683
Brotchie P, Iansek R, Horne MK (1991b) Motor function of the monkey globus pallidus. 2. Cognitive aspects of movement. Brain 114:1685–1702
Brown VJ, Robbins TW (1989) Elementary processes of responses selection mediated by distant regions of the striatum. J Neurosci 9:3761–3765
Cheruel F, Dormont JF, Amalric M, Schmied A, Farin D (1994) The role of putamen and pallidum in motor initiation in the cat. I. Timing of movement-related single unit activity. Exp Brain Res 100:250–266
Condé H, Bénita M, Dormont JF, Schmied A, Cadoret A (1981) Control of reaction time performance involves the striatum. J Physiol (Paris) 77:97–105
Cools AR, Spooren W, Bezemer R, Cuypers E, Jaspers R, Groenewegen H (1989) Anatomically distinct output channels of the caudate nucleus and orofacial dyskinesia: critical role of the subcommissural part of the globus pallidus in oral dyskinesia. Neuroscience 33:535–542
Crossman AR (1987) Primate models of dyskinesia: experimental approach to the study of basal ganglia-related involuntary movement disorders. Neuroscience 21:1–40
DeLong MR (1971) Activity of pallidal neurons during movement. J Neurophysiol 34:414–427
DeLong MR (1990) Primate models of movement disorders of basal ganglia origin. Trends Neurosci 13:281–285
DeLong MR, Georgopoulos AP (1981) Motor functions of the basal ganglia. In: Brooks VB (Handbook of physiology, sect 1. The nervous system, vol II, part 2) Bethesda, Md. Motor control. Am Physiol Soc, Chap. 21, pp 1017–1061
DeLong MR, Crutcher MD, Georgopoulos AP (1985) Primate globus pallidus and subthalamic nucleus: functional organization. J Neurophysiol 53:530–543
Di Chiara G, Porceddu M, Imperato A, Morelli M (1981) Role of GABA neurons in the expression of striatal motor functions. In: Di Chiara G, Gessa G (eds) GABA and the basal ganglia. Raven, New York, pp 129–163
Dormont JF, Farin D, Rougui Z, Schmied A, Amalric M, Cheruel F (1991) Single unit activity related to motor initiation in the cat pallidum. Eur J Neurosci [Suppl] 4:152
Faull RLM, Waldvogel HJ, Nicholson LFB, Synek BJL (1993) The distribution of GABAA-benzodiazepine receptors in the basal ganglia in Huntington's disease and in the quinolonic acid-lesioned rat. Prog Brain Res. 99:105–123
Gardiner TW, Kitai ST (1992) Single-unit activity in the globus pallidus and neostriatum of the rat during performance of a trained head movement. Exp Brain Res 88:517–530
Georgopoulos AP, DeLong MR, Crutcher MD (1983) Relations between parameters of strep-tracking movements and single cell discharge in the globus pallidus and subthalamic nucleus of the behaving monkey. J Neurosci 3:1586–1598
Gerfen CR (1984) The neostriatal mosaïc: compartmentalization of cortico-striatal input and striatonigral output systems. Nature 311:461–464
Hamada I, DeLong MR, Mano NI (1990) Activity of identified wrist-related pallidal neurons during step and ramp wrist movements in the monkey. J Neurophysiol 64:1892–1906
Hedreen JC, DeLong M (1991) Organization of striatopallidal, striatonigral and nigrostriatal projections in the macaque. J Comp Neurol 304:569–595
Horak FB, Anderson ME (1984) Influence of globus pallidus on arm movements in monkeys. I. Effects of kainic acid-induced lesions. J Neurophysiol 52:290–304
Hore J, Vilis T (1980) Arm movement performance during reversible basal ganglia lesions in the monkey. Exp Brain Res 39:217–228
Itoh M (1983) Effect of haloperidol on glutamate decarboxylase activity in discrete brain areas of the rat. Psychopharmacology 79:169–172
Jasper HH, Ajmone-Marsan C (1954) A stereotaxic atlas of the diencephalon of the cat. National Res Council of Canada, Ottawa
Kato M, Kimura M (1992) Effects of reversible blockade of basal ganglia on a voluntary arm movement. J Neurophysiol 68:1516–1534
Kelly J, Rothstein J, Grossman SP (1979) GABA and hypothalamic feeding system. I. Topographic analysis of the effects of microinjections of muscimol. Physiol Behav 23:1123–1134
Kimura M, Kato M, Shimazaki H (1990) Physiological properties of projection neurons in the monkey striatum to the globus pallidus. Exp Brain Res 82:672–676
Marsden CD (1982) The mysterious motor function of the basal ganglia. Neurology 32:514–539
Marsden CD (1992) Dopamine and basal ganglia disorders in humans. Semin Neurosci 4:171–178
Mink JW, Thach WT (1991) Basal ganglia motor control. III. Pallidal ablation: normal reaction time, muscle cocontraction, and slow movement. J Neurophysiol 65:330–351
Mitchell SL, Richardson RT, Baker FH, DeLong MR (1987) The primate globus pallidus: neuronal activity related to direction of movement. Exp Brain Res 68:491–505
Moriizuri T, Hattori T (1992) Separate neuronal populations of the rat globus pallidus projecting to the subthalamic nucleus, auditory cortex and pedunculopontine tegmental area. Neuroscience 46:701–710
Moriizumi T, Nakamura Y, Okoyama S, Kitao Y (1987) Synaptic organization of the cat entopeduncular nucleus with special reference to the relationship between the afferents to entopedunculothalamic projection neurons: an electron microscope study by a combined degeneration and horseradish peroxidase tracing technique. Neuroscience 20:797–816
Nambu A, Yoshida SI, Jinnai K (1990) Discharge patterns of pallidal neurons with input from various cortical areas during movement in the monkey. Brain Res 519:183–191
Neafsey EJ, Hull CD, Buchwald NA (1978) Preparation for movement in the cat. II. Unit activity in the basal ganglia and thalamus. Electroencephalogr Clin Neurophysiol 44:714–723
Nieoullon A, Kerkerian-LeGoff L (1992) Cellular interactions in the striatum involving neuronal systems using “classical” neurotransmitters: possible functional implications. Mov Disord 7:311–325
Nishino H, Ono T, Muramoto KI, Fukuda M, Sasaki K (1985) Movement and non-movement related pallidal unit activity during bar press feeding behavior in the monkey. Behav Brain Res 15:27–42
Pycock CJ, Horton RW, Marsden CD (1976) The behavioural effects of manipulating GABA function in the globus pallidus. Brain Res 116:353–359
Reavill C, Jenner P, Marsden CD (1984) Gamma-aminobutyric acid and basal ganglia outflow pathways. In: Evered D, O'Connor M (eds) Functions of the basal ganglia. Pittman, London, pp 164–171
Scheel-Krüger J (1986) Dopamine-GABA interactions: evidence that GABA transmits, modulates and mediates dopaminergic functions in the basal ganglia and the limbic system. Acta Neurol Scand 73:9–54
Scheel-Krüger J, Magelund G (1981) GABA in the entopeduncular nucleus and the subthalamic nucleus participates in mediating dopaminergic striatal output functions. Life Sci 29:1555–1562
Scheel-Krüger J, Magelund G, Olianas MC (1981) Role of GABA in the striatal output systems: globus pallidus, nucleus entopeduncularis, substantia nigra and nucleus subthalamicus. In: Di Chiara G, Gessa GL (eds) GABA and the basal ganglia Raven, New-York, pp 165–186
Schmied A, Amalric M, Dormont JF, Farin D (1990) GABAergic mechanisms in the cat red nucleus: effects of intracerebral microinjections of muscimol or bicuculline on a conditioned motor task. Exp Brain Res 81:523–532
Schmied A, Amalric M, Dormont JF, Farin D (1991) GABAergic control of rubral single unit activity during a reaction time task. Exp Brain Res 84:285–296
Schmued L, Phermsangngam P, Lee H, Thio S, Chen E, Truong P, Colton E, Fallon J (1989) Collaterization and GAD immunoreactivity of descending pallidal efferents. Brain Res 487:131–142
Trouche E, Beaubaton D, Amato G, Viallet F, Legallet E (1984) Changes in reaction time after pallidal or nigral lesion in the monkey. Adv Neurol 40:29–38
Winer BJ (1971) Statistical principles in experimental design. McGraw-Hill, New York, p 672
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Amalric, M., Farin, D., Dormont, J.F. et al. GABA-receptor activation in the globus pallidus and entopeduncular nucleus: opposite effects on reaction time performance in the cat. Exp Brain Res 102, 244–258 (1994). https://doi.org/10.1007/BF00227512
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DOI: https://doi.org/10.1007/BF00227512