Summary
The spontaneous activity of neurons in the head of the striatum was studied in rats 3 days and more than 1 year after a 6-hydroxydopamine-induced lesion of the nigrostriatal dopamine system in comparison to unlesioned animals. Cells were detected and tracked by stimulating the excitatory corticostriatal pathway.
In unlesioned animals striatal cells discharged at very low frequencies, with a median of 0.04 impulses/second. The activity was increased to 0.28 impulses/second 3 days after the lesion. This increase was related to the degree of dopamine depletion. More than 1 year after the lesion, the frequency had decreased to a level indistinguishable from that measured in unlesioned animals, with a median of 0.03 impulses/second. Cells in 3-day lesioned animals discharged a higher number of bursts at shorter intervals as compared to unlesioned animals, while in long-term denervated animals the bursting pattern was similar to that in unlesioned animals.
This demonstrates that removal of the dopaminergic input results in increased activity only during an initial phase and that adaptive processes subsequently occur. The data from this Parkinsonian model suggest that symptoms of this disease cannot simply be related to an increased striatal cellular activity. The fact that the initially increased spontaneous activity adapted indicates that functional effects of a lesion can only be evaluated when studying the resulting changes throughout a time course.
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References
Bloom, F.E.: Fine structural changes in rat brain after intracisternal injection of 6-hydroxy-dopamine. In: 6-Hydroxydopamine and Catecholamine Neurons (eds. T. Malmfors and H. Thoenen), pp. 135–150. Amsterdam: North-Holland 1971
Bloom, F.E., Costa, E., Salmoiraghi, G.C.: Anesthesia and the responsiveness of individual neurons of the caudate nucleus of the rat to acetylcholine, norepinephrine and dopamine administered by microelectrophoresis. J Pharmacol Exp Ther 150, 244–252 (1965)
Buchwald, N.A., Price, D.D., Vernon, L., Hull, C.D.: Caudate intracellular response to thalamic and cortical inputs. Exp Neurol 38, 311–323 (1973)
Bunney, B.S., Walters, J.R., Roth, R.H., Aghajanian, G.K.: Dopamine neurons: Effect of antipsychotic drugs and amphetamine on single cell activity. J Pharmacol Exp Ther 185, 560–571 (1973)
Connor, J.D.: Caudate nucleus neurons: Correlation of the effects of substantia nigra stimulation with iontophoretic dopamine. J Physiol (Lond) 208, 691–703 (1970)
DeLong, M.: Putamen: Activity of single units during slow and rapid movements. Science 179, 1240–1242 (1973)
Feltz, P.: Dopamine, amino acids and caudate unitary responses to nigral stimulation. J Physiol (Lond) 205, 8–9P (1970)
Feltz, P., De Champlain, J.: Enhanced sensitivity of caudate neurons to microiontophoretic injections of dopamine in 6-hydroxydopamine treated rats. Brain Res 43, 601–605 (1972)
Fuxe, K., Hökfelt, T., Jonsson, G., Ungerstedt, U.: Fluorescence microscopy in neuroanatomy. In: Contemporary Research Methods in Neuroanatomy (eds. S. Ebbeson and W. Nauta), pp. 275–314. New York: Springer 1970
Gonzalez-Vegas, J.A.: Antagonism of dopamine-mediated inhibition in the nigro-striatal pathway: a mode of action of some catatonia inducing drugs. Brain Res. 80, 219–228 (1974)
Hattori, T., Fibiger, H.C., McGeer, P.L., Malwr, L.: Analysis of the fine structure of the dopaminergic nigrostriatal projection by electron microscopic autoradiography. Exp Neurol 41, 599–611 (1973)
Herz, A., Zieglgänsberger, W.: The influence of microelectrophoretically applied biogenic amines, cholinomimetics and procain on synaptic excitation in the corpus striatum. Int J Neuropharmacol 7, 221–230 (1968)
Hoffer, B.J., Siggins, G.R., Woodward, D.J., Bloom, F.E.: Spontaneous discharge of Purkinje neurons after destruction of catecholamine-containing afferents by 6-hydroxydopamine. Brain Res 30, 425–430 (1971)
Hökfelt, T., Ungerstedt, U.: Specificity of 6-hydroxydopamine induced degeneration of central monoamine neurons. An electron and fluorescence microscopic study with special reference to intracerebral injection on the nigrostriatal dopamine system. Brain Res 60, 269–298 (1973)
Hornykiewicz, O.: Dopamine (3-hydroxytyramine) and brain function. Pharmacol Rev 18, 925–964 (1966)
Hull, C.D., Levine, M.S., Buchwald, N.A., Heller, A., Browning, R.A.: The spontaneous firing pattern of forebrain neurons. I. The effects of dopamine and non-dopamine depleting lesions on caudate firing patterns. Brain Res. 73, 241–262 (1974)
Keller, R., Oke, A., Mefford, I., Adams, R.N.: Liquid chromatographic analysis of catecholamines. Routine assay for regional brain mapping. Life Sci 19, 995–1004 (1976)
Kemp, J.M., Powell, T.P.S.: The site of termination of afferent fibres in the caudate nucleus. Phil Trans Roy Soc Lond B 262, 413–427 (1971)
Kitai, S.T., Kocsis, J.D., Preston, R.J., Sugimori, M.: Monosynaptic inputs to caudate neurons identified by intracellular injection of horseradish peroxidase. Brain Res 109, 601–606 (1976a)
Kitai, S.T., Sugimori, M., Kocsis, J.D.: Excitatory nature of dopamine in the nigro-caudate pathway. Exp. Brain Res 24, 351–363 (1976b)
König, J.F.R., Klippel, R.A.: The Rat Brain: A Stereotaxic Atlas of the Forebrain and Lower Parts of the Brain Stem. Baltimore: Williams and Wilkins 1963
McGeer, P.L., McGeer, E.G.: Evidence for glutamic acid decarboxylase-containing interneurons in the neostriatum. Brain Res 91, 331–335 (1975)
McLennan, H., York, D.H.: The action of dopamine on neurons of the caudate nucleus. J Physiol (Lond) 189, 393–402 (1967)
Niki, H., Sakai, M., Kubota, K.: Delayed alternation performance and unit activity of the caudate head and medial orbitofrontal gyrus in the monkey. Brain Res 38, 343–353 (1972)
Norcross, K., Spehlmann, R.: Selective blockade of excitatory caudate responses to nigral stimulation by microiontophoretic application of dopamine antagonists. Neurosci Letters 6, 323–328 (1977)
Ohye, C., Bouchard, R., Boucher, R., Poirier, L.J.: Spontaneous activity of the putamen after chronic interruption of the dopaminergic pathway: Effect of L-dopa. J Pharmacol Exp Ther 175, 700–708 (1970)
Ranje, C., Ungerstedt, U.: High correlations between number of dopamine cells, dopamine levels and motor performance. Brain Res 134, 83–93 (1977)
Raisman, G.: Neuronal plasticity in the septal nuclei of the adult rat. Brain Res 14, 25–48 (1969)
Richardson, T.L., Miller, J.J., McLennan, H.: Mechanisms of excitation and inhibition in the nigrostriatal system. Brain Res 127, 219–234 (1977)
Schultz, W., Ungerstedt, U.: A method to detect and record from striatal cells of low spontaneous activity by stimulating the corticostriatal pathway. Brain Res 142, 357–362 (1978a)
Schultz, W., Ungerstedt, U.: Striatal cell supersensitivity to apomorphine in dopamine lesioned rats correlated to behaviour. Neuropharmacology (in press) (1978b)
Siegel, S.: Nonparametric Statistics for the Behavioral Sciences. New York: McGraw Hill 1956
Siggins, G.R., Hoffer, B.J., Bloom, F.E., Ungerstedt, U.: Cytochemical and electrophysiological studies of dopamine in the caudate nucleus. In: The Basal Ganglia (ed. M.D. Yahr), pp. 227–248. New York: Raven Press 1976
Siggins, G.R., Hoffer, B.J., Ungerstedt, U.: Electrophysiological evidence for involvement of cyclic adenosine monophosphate in dopamine responses of caudate neurons. Life Sci 15, 779–792 (1974)
Spehlmann, R.: The effects of acetylcholine and dopamine on the caudate nucleus depleted of biogenic amines. Brain 98, 219–230 (1975)
Spehlmann, R., Norcross, K., Grimmer, E.: GABA in the caudate nucleus: A possible synaptic transmitter of interneurons. Experientia (Basel) 33, 623–625 (1977)
Spencer, H.J.: Antagonism of cortical excitation of striatal neurons by glutamic acid diethyl ester: Evidence for glutamic acid as an excitatory transmitter in the rat striatum. Brain Res 102, 91–101 (1976)
Steg, G.: Striatal cell activity during systemic administration of monoaminergic and cholinergic drugs. In: Third Symposium on Parkinson's Disease (eds. F. Gillingham, I. Donaldson), pp. 26–29. Edinburgh: Livingstone 1969
Tsukahara, N., Hultborn, H., Murakami, F., Fujito, Y.: Electrophysiological study of formation of nerve synapses and collateral sprouting in red nuclear neurons after partial denervation. J Neurophysiol 38, 1359–1372 (1975)
Ungerstedt, U.: Stereotaxic mapping of the monoamine pathways in rat brain. Acta Physiol Scand Suppl. 367, 1–48 (1971)
Webster, K.E.: Cortico-striate interrelations in the albino rat. J Anat (Lond) 95, 532–544 (1961)
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Schultz, W., Ungerstedt, U. Short-Term increase and long-term reversion of striatal cell activity after degeneration of the nigrostriatal dopamine system. Exp Brain Res 33, 159–171 (1978). https://doi.org/10.1007/BF00238057
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DOI: https://doi.org/10.1007/BF00238057