Short-Term increase and long-term reversion of striatal cell activity after degeneration of the nigrostriatal dopamine system

SummaryThe 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.

[1]  U. Ungerstedt Stereotaxic mapping of the monoamine pathways in the rat brain. , 1971, Acta physiologica Scandinavica. Supplementum.

[2]  M. Sugimori,et al.  Monosynaptic inputs to caudate neurons identified by intracellular injection of horseradish peroxidase , 1976, Brain Research.

[3]  F. Bloom,et al.  Spontaneous discharge of Purkinje neurons after destruction of catecholamine-containing afferents by 6-hydroxydopamine. , 1971, Brain research.

[4]  N. A. Buchwald,et al.  Caudate intracellular response to thalamic and cortical inputs. , 1973, Experimental neurology.

[5]  U. Ungerstedt,et al.  Electrophysiological evidence for involvement of cyclic adenosine monophosphate in dopamine responses of caudate neurons , 1974 .

[6]  J D Connor,et al.  Caudate nucleus neurones: correlation of the effects of substantia nigra stimulation with iontophoretic dopamine , 1970, The Journal of physiology.

[7]  M. Delong,et al.  Putamen: Activity of Single Units during Slow and Rapid Arm Movements , 1973, Science.

[8]  Joachim F. R. König,et al.  The rat brain: A stereotaxic atlas of the forebrain and lower parts of the brain stem , 1986 .

[9]  N. Tsukahara,et al.  Electrophysiological study of formation of new synapses and collateral sprouting in red nucleus neurons after partial denervation. , 1975, Journal of neurophysiology.

[10]  B J Hoffer,et al.  Cytochemical and electrophysiological studies of dopamine in the caudate nucleus. , 1976, Research publications - Association for Research in Nervous and Mental Disease.

[11]  P. Feltz Dopamine, amino acids and caudate unitary responses to nigral stimulation. , 1969, The Journal of physiology.

[12]  Bernice W. Polemis Nonparametric Statistics for the Behavioral Sciences , 1959 .

[13]  W. Zieglgänsberger,et al.  The influence of microelectrophoretically applied biogenic amines, cholinomimetics and procaine on synaptic excitation in the corpus striatum. , 1968, International journal of neuropharmacology.

[14]  Webster Ke Cortico-striate interrelations in the albino rat. , 1961 .

[15]  O. Hornykiewicz Dopamine (3-hydroxytyramine) and brain function. , 1966, Pharmacological reviews.

[16]  U. Ungerstedt,et al.  High correlations between number of dopamine cells, dopamine levels and motor performance , 1977, Brain Research.

[17]  H. Mclennan,et al.  Mechanisms of excitation and inhibition in the nigrostriatal system , 1977, Brain Research.

[18]  G Raisman,et al.  Neuronal plasticity in the septal nuclei of the adult rat. , 1969, Brain research.

[19]  F. Bloom,et al.  Anesthesia and the responsiveness of individual neurons of the caudate nucleus of the cat to acetylcholine, norepinephrine and dopamine administered by microelectrophoresis. , 1965, The Journal of pharmacology and experimental therapeutics.

[20]  W. Schultz,et al.  A method to detect and record from striatal cells of low spontaneous activity by stimulating the corticostriatal pathway , 1978, Brain Research.

[21]  H. Mclennan,et al.  The action of dopamine on neurones of the caudate nucleus , 1967, The Journal of physiology.

[22]  T. Hökfelt,et al.  Specificity of 6-hydroxydopamine induced degeneration of central monoamine neurones: an electron and fluorescence microscopic study with special reference to intracerebral injection on the nigro-striatal dopamine system. , 1973, Brain research.

[23]  H. Niki,et al.  Delayed alternation performance and unit activity of the caudate head and medial orbitofrontal gyrus in the monkey. , 1972, Brain research.

[24]  A. Oke,et al.  Liquid chromatographic analysis of catecholamines routine assay for regional brain mapping. , 1976, Life sciences.

[25]  C. Ohye,et al.  Spontaneous activity of the putamen after chronic interruption of the dopaminergic pathway: effect of L-dopa. , 1970, The Journal of pharmacology and experimental therapeutics.

[26]  H. Fibiger,et al.  Analysis of the fine structure of the dopaminergic nigrostriatal projection by electron microscopic autoradiography. , 1973, Experimental neurology.

[27]  R. Spehlmann The effects of acetylcholine and dopamine on the caudate nucleus depleted of biogenic amines. , 1975, Brain : a journal of neurology.

[28]  R. Spehlmann,et al.  GABA in the caudate nucleus: A possible synaptic transmitter of interneurons , 1977, Experientia.

[29]  P. Mcgeer,et al.  Evidence for glutamic acid decarboxylase-containing interneurons in the neostriatum , 1975, Brain Research.

[30]  W. Schultz,et al.  Striatal cell supersensitivity to apomorphine in dopamine-lesioned rats correlated to behaviour , 1978, Neuropharmacology.

[31]  T. Powell,et al.  The site of termination of afferent fibres in the caudate nucleus. , 1971, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[32]  Hugh J. Spencer Antagonism of cortical excitation of striatal neurons by glutamic acid diethyl ester: Evidence for glutamic acid as an excitatory transmitter in the rat striatum , 1976, Brain Research.

[33]  R. Roth,et al.  Dopaminergic neurons: effect of antipsychotic drugs and amphetamine on single cell activity. , 1973, The Journal of pharmacology and experimental therapeutics.

[34]  J. de Champlain,et al.  Enhanced sensitivity of caudate neurones to microiontophoretic injections of dopamine in 6-hydroxydopamine treated cats. , 1972, Brain research.

[35]  T. Hökfelt,et al.  Fluorescence Microscopy in Neuroanatomy , 1970 .

[36]  R. Spehlmann,et al.  Selective blockade of excitatory caudate responses to nigral stimulation by microiontophoretic application of dopamine antagonists , 1977, Neuroscience Letters.

[37]  N. A. Buchwald,et al.  The spontaneous firing pattern of forebrain neurons. I. The effects of dopamine and non-dopamine depleting lesions on caudate unit firing patterns. , 1974, Brain research.

[38]  J. A. González-Vegas Antagonism of dopamine-mediated inhibition in the nigro-striatal pathway: a mode of action of some catatonia-inducing drugs. , 1974, Brain research.

[39]  M. Sugimori,et al.  Excitatory nature of dopamine in the nigro-caudate pathway , 1976, Experimental Brain Research.