Evolution of changes in neuronal activity in the subthalamic nucleus of rats with unilateral lesion of the substantia nigra assessed by metabolic and electrophysiological measurements

Cellular expression of cytochrome oxidase subunit I (COI) mRNA has recently been used as a metabolic marker for neuronal activity to study the functional changes in the subthalamic nucleus (STN) in parkinsonism. The previous experimental studies have been performed when the pathological state was stabilized at a maximal level. In order to determine the evolution of changes in neuronal activity in the STN after nigrostriatal denervation, we analysed by in situ hybridization the cellular expression of COI mRNA in the subthalamic neurons at different times, from 6 h to 14 days, after unilateral intranigral microinjection of 6‐hydroxydopamine (6‐OHDA) in rats. In parallel, the time‐dependent changes of the unit neuronal activity of subthalamic neurons have been recorded. Levels of COI mRNA increased by 41% in subthalamic neurons from 24 h after 6‐OHDA intoxication, to 14 days (+26%). Similarly, electrical activity started to increase slightly 24 h after lesion (+20%) and remained significantly higher at 14 days after the lesion (+189%). Changes in neuronal mean discharge rate were associated with changes in the pattern of spiking activity, from a regular firing pattern to an irregular one with a high bursting activity. These results show that: (i) the hyperactivity of the STN represents a very early phenomenon in the physiopathology of parkinsonian syndromes; and (ii) that changes in COI mRNA expression slightly precede changes in electrical neuronal activity.

[1]  Y Agid,et al.  Systemic Administration of NMDA and AMPA Receptor Antagonists Reverses the Neurochemical Changes Induced by Nigrostriatal Denervation in Basal Ganglia , 1999, Journal of neurochemistry.

[2]  N. Lindefors,et al.  Increased expression of glutamic acid decarboxylase mRNA in rat substantia nigra after an ibotenic acid lesion in the caudate-putamen. , 1990, Brain research. Molecular brain research.

[3]  J. Aceves,et al.  Appearance of EMG activity and motor asymmetry after unilateral lesions of the dopaminergic innervation to the subthalamic nucleus in the rat , 1993, Neuroscience Letters.

[4]  A. Benabid,et al.  Effect on parkinsonian signs and symptoms of bilateral subthalamic nucleus stimulation , 1995, The Lancet.

[5]  J P Changeux,et al.  Detection of the nicotinic acetylcholine receptor alpha‐subunit mRNA by in situ hybridization at neuromuscular junctions of 15‐day‐old chick striated muscles. , 1988, The EMBO journal.

[6]  A. Crossman.  Neural mechanisms in disorders of movement. , 1989, Comparative biochemistry and physiology. A, Comparative physiology.

[7]  C. Feuerstein,et al.  Similar Time Course Changes in Striatal Levels of Glutamic Acid Decarboxylase and Proenkephalin mRNA Following Dopaminergic Deafferentation in the Rat , 1988, Journal of neurochemistry.

[8]  W J Schwartz,et al.  Metabolic mapping of functional activity in the hypothalamo-neurohypophysial system of the rat. , 1979, Science.

[9]  J A Obeso,et al.  Consequences of Nigrostriatal Denervation on the Functioning of the Basal Ganglia in Human and Nonhuman Primates: An In Situ Hybridization Study of Cytochrome Oxidase Subunit I mRNA , 1997, The Journal of Neuroscience.

[10]  M. Wong-Riley,et al.  Neuronal expression of nuclear and mitochondrial genes for cytochrome oxidase (CO) subunits analyzed by in situ hybridization: comparison with CO activity and protein , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[11]  E. Hirsch,et al.  Subthalamotomy in parkinsonian monkeys. Behavioural and biochemical analysis. , 1996, Brain : a journal of neurology.

[12]  J Astrup,et al.  Oxygen and glucose consumption related to Na+-K+ transport in canine brain. , 1981, Stroke.

[13]  T. Itakura,et al.  Intrastriatal Mesencephalic Grafts Affect Neuronal Activity in Basal Ganglia Nuclei and Their Target Structures in a Rat Model of Parkinson’s Disease , 1998, The Journal of Neuroscience.

[14]  J. Brotchie,et al.  Alleviation of parkinsonism by antagonism of excitatory amino acid transmission in the medial segment of the globus pallidus in rat and primate , 1991, Movement disorders : official journal of the Movement Disorder Society.

[15]  B Bioulac,et al.  Reversal of Rigidity and Improvement in Motor Performance by Subthalamic High‐frequency Stimulation in MPTP‐treated Monkeys , 1993, The European journal of neuroscience.

[16]  C. Marescaux,et al.  Contralateral disappearance of parkinsonian signs after subthalamic hematoma , 1992, Neurology.

[17]  L. Naudon,et al.  Reserpine Affects Differentially the Density of the Vesicular Monoamine Transporter and Dihydrotetrabenazine Binding Sites , 1996, The European journal of neuroscience.

[18]  J. Penney,et al.  The functional anatomy of basal ganglia disorders , 1989, Trends in Neurosciences.

[19]  T. Klockgether,et al.  The AMPA receptor antagonist NBQX has antiparkinsonian effects in monoamine‐depleted rats and MPTP‐treated monkeys , 1991, Annals of neurology.

[20]  N. Canteras,et al.  Somatosensory inputs to the subthalamic nucleus: a combined retrograde and anterograde horseradish peroxidase study in the rat , 1988, Brain Research.

[21]  M. Delong,et al.  Primate models of movement disorders of basal ganglia origin , 1990, Trends in Neurosciences.

[22]  R. Kurlan,et al.  Antiparkinsonian effects of remacemide hydrochloride, a glutamate antagonist, in rodent and primate models of Parkinson's disease , 1994, Annals of neurology.

[23]  J. Greenamyre,et al.  Polysynaptic regulation of glutamate receptors and mitochondrial enzyme activities in the basal ganglia of rats with unilateral dopamine depletion , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[24]  M. Wong-Riley,et al.  Effect of impulse blockage on cytochrome oxidase activity in monkey visual system , 1984, Nature.

[25]  Louis Sokoloff,et al.  Activity‐dependent Energy Metabolism in Rat Posterior Pituitary Primarily Reflects Sodium Pump Activity , 1980, Journal of neurochemistry.

[26]  Jean Féger,et al.  The Effects of Activation or Inhibition of the Subthalamic Nucleus on the Metabolic and Electrophysiological Activities Within the Pallidal Complex and Substantia Nigra in the Rat , 1991, The European journal of neuroscience.

[27]  H. Bergman,et al.  Reversal of experimental parkinsonism by lesions of the subthalamic nucleus. , 1990, Science.

[28]  Allan J. Tobin,et al.  Parallel increases in striatal glutamic acid decarboxylase activity and mRNA levels in rats with lesions of the nigrostriatal pathway , 1990, Brain Research.

[29]  G. E. Alexander,et al.  Functional architecture of basal ganglia circuits: neural substrates of parallel processing , 1990, Trends in Neurosciences.

[30]  K. Chergui,et al.  Burst stimulation of the medial forebrain bundle selectively increases Fos-like immunoreactivity in the limbic forebrain of the rat , 1996, Neuroscience.

[31]  I. Lucki,et al.  Dopaminergic Stimulation of Subthalamic Nucleus Elicits Oral Dyskinesia in Rats , 1994, Experimental Neurology.

[32]  O. Hassani,et al.  Evidence for a dopaminergic innervation of the subthalamic nucleus in the rat , 1997, Brain Research.

[33]  A. Parent,et al.  Increased glutamate decarboxylase mRNA levels in the striatum and pallidum of MPTP-treated primates , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[34]  J. A. Obeso,et al.  Metabolic activity of the basal ganglia in parkinsonian syndromes in human and non-human primates: A cytochrome oxidase histochemistry study , 1996, Neuroscience.

[35]  R. Hevner,et al.  Coordination of ATP production and consumption in brain: Parallel regulation of cytochrome oxidase and Na+, K+-ATPase , 1992, Neuroscience Letters.

[36]  F. Gonon.  Nonlinear relationship between impulse flow and dopamine released by rat midbrain dopaminergic neurons as studied by in vivo electrochemistry , 1988, Neuroscience.

[37]  M. Bevan,et al.  The projections from the parafascicular thalamic nucleus to the subthalamic nucleus and the striatum arise from separate neuronal populations: A comparison with the corticostriatal and corticosubthalamic efferents in a retrograde fluorescent double-labelling study , 1994, Neuroscience.

[38]  R. G. Robertson,et al.  Neural mechanisms underlying parkinsonian symptoms based upon regional uptake of 2-deoxyglucose in monkeys exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine , 1989, Neuroscience.

[39]  M. Delong,et al.  Pathophysiology of parkinsonian motor abnormalities. , 1993, Advances in neurology.

[40]  I. Silver,et al.  ATP and Brain Function , 1989, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[41]  T. Klockgether,et al.  NMDA antagonists potentiate antiparkinsonian actions of L‐dopa in monoamine‐depleted rats , 1990, Annals of neurology.

[42]  M. Wong-Riley,et al.  Regulation of cytochrome oxidase protein levels by functional activity in the macaque monkey visual system , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[43]  T. Aziz,et al.  Lesion of the subthalamic nucleus for the alleviation of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐induced parkinsonism in the primate , 1991, Movement disorders : official journal of the Movement Disorder Society.

[44]  J. Vitek,et al.  Burst and oscillation as disparate neuronal properties , 1996, Journal of Neuroscience Methods.

[45]  L. Swanson.  The Rat Brain in Stereotaxic Coordinates, George Paxinos, Charles Watson (Eds.). Academic Press, San Diego, CA (1982), vii + 153, $35.00, ISBN: 0 125 47620 5 , 1984 .

[46]  G. Uhl,et al.  Dopamine transporter immunoreactivity in rat brain , 1995, The Journal of comparative neurology.

[47]  C. W. Ragsdale,et al.  Histochemically distinct compartments in the striatum of human, monkeys, and cat demonstrated by acetylthiocholinesterase staining. , 1978, Proceedings of the National Academy of Sciences of the United States of America.

[48]  Y. Agid,et al.  Long‐Term Induction of Tyrosine Hydroxylase Expression: Compensatory Response to Partial Degeneration of the Dopaminergic Nigrostriatal System in the Rat Brain , 1995, Journal of neurochemistry.