Effect of substantia nigra stimulation on spontaneous unit activity in the caudate nucleus

A wide range of spontaneous unit activity (0.1–15 spikes/sec) was observed in the caudate nucleus of rats anesthetized with urethane. All units did not respond by driven activity following stimulation of the substantia nigra. However, 71% of this population responded by significantly increased or decreased firing rates. It is suggested that unit that exhibit spontaneous activity in the caudate nucleus and which respond to stimulation of the substantia nigra have polysynaptic connections, and those units which do not discharge spontaneously but respond to stimulation of the substantia nucleus by driven action potentials have monosynaptic connetion to the caudate nucleus.     

Altered caudate nucleus field potentials following sustained stimulation to different substantia nigra regions

Evoked potential recording techniques were used as a physiological tool for electrode placement into the substantia nigra pars compacta (SNpc). It was found that when the recording electrodes were implanted at the level of the caudate nucleus (CN), typical patterns were obtained only when the stimulation electrode was located in the SNpc. When the stimulation electrode was fixed in the SNpc and four electrodes were simultaneously used to record depth profile from the caudate nucleus and the septum, the typical responses following stimulation were obtained only when electrodes were within the CN head. High frequency stimulation of the SNpc, which is known to alter dopamine content within the CN, caused a reversible diminution of responses in CN for 5-10 min. This observation was discussed in terms of terminal transmitter depletion.     

Responses of cat cerebellar cortex neurons to stimulation of the caudate nucleus, globus pallidus and substantia nigra

Impulsive responses (IR) of the Purkinje cells (PC) and other units of the cerebellar cortex in the paramedian lobules, lobulus simplex and tuber vermis were evoked by stimulation of nucleus caudatus (NC) in cats under chloraloze-nembutal narcosis. The phasic IR as simple discharges (due to mossy fibre activation) were exhibited mainly with a latency of 5-12 and 14-20 ms; a latency of the compound responses ) due to climbing fibre PC activation) was equal to 5-6, 9-22 ms and more. There were differences in rhythmic reproduction of the responses depending on their latency. The recruitment responses were found during a 4-6/s NC stimulation. There was an inhibitory pause as an obligatory component of the tonic neuronal responses. Reactions of the same types (phasic and tonic) as in the case of the NC stimulation, but differing in unit's quantitative distribution according to the latency appeared in the globus pallidus (GP) stimulation. The minimal latency was 4 ms. Recruitment was observed as well. The substantia nigra (SN) stimulation evoked PC responses, activated by the climbing fibres with a stable latency (8.5 +/- 0.3 ms). SN, GP, n. inferior olive as well as thalamic nuclei are considered to play a definite role in realizing caudate-cerebellar connections, both oligosynaptic and polysynaptic.     

Muscimol suppresses rCGU increase in the substantia nigra after destruction of the caudate nucleus.

Injection of ibotenic acid into the caudate nucleus caused an increase in the uptake of 2-deoxyglucose (2DG) in the ipsilateral substantia nigra pars reticulata (SNr). Increased 2DG uptake was completely suppressed by chronic infusion of muscimol, the gamma-aminobutyric acid (GABA) agonist. While delayed shorter infusion of muscimol from the 3rd to the 7th day, when 2DG accumulation was the most prominent, partially prevented this increase. These data suggest that GABA-mediated transneuronal processes play an important role in the delayed elevation in 2DG uptake in SNR but hyperexcitation due to disinhibition by the loss of GABAergic inputs may play only a partial role in this increase.     

Inhibition of neuronal activity of the substantia nigra by noxious stimuli and its modification by the caudate nucleus

In urethane-anesthetized rats discharges of neurons of substantia nigra, pars compacta (SNC) were recorded extracellularly after natural somatic sensory stimulation and electrical stimulation of peripheral sensory nerves.

(1) Among different modalities of somatic sensory stimulation tested, noxious stimuli were effective in reducing spontaneous discharges of SNC neurons. The inhibition appeared with a concomitant increase of spike amplitude. The same inhibitory effect was obtained by stimulating the sciatic nerve (SC) repetitively. In response to single shock stimulation of the SC the inhibition occurred at an average latency of 39.6 msec (S.E. 1.6 msec) and lasted for 221.6 msec on average (S.E. 10.8 msec).

(2) The SC-induced inhibition of SNC neurons failed to reliably block orthoand antidromic discharges evoked from the caudate nucleus (Cd).

(3) In rats with the Cd lesioned the SC-induced inhibition was longer lasting than in controls. When the Cd was stimulated concurrently with SC stimulation, the inhibition from the SC was weakened.

(4) In a majority of SNC neurons, their inhibition by SC stimulation was antagonized by intravenous injection of haloperidol.

DARPP-32 development in the caudate nucleus is independent of afferent input from the substantia nigra

DARPP-32, a dopamine- and adenosine 3':5'-monophosphate regulated neuronal phosphoprotein, Mr 32 kDa, is a phenotypic marker of the medium-size spiny neurons of the mammalian caudate-putamen. In the present study, we examined the ontogeny of DARPP-32 protein and mRNA, and compared it to the ontogeny of tyrosine hydroxylase and synapsin I, a synaptic-vesicle phosphoprotein. In vivo, the amount of DARPP-32 protein per mg total protein increased throughout the first three postnatal weeks, and then declined to plateau at adult levels. The mRNA level closely paralleled the protein, except that its rise preceded that of the protein. Tyrosine hydroxylase levels rose throughout the first 4 postnatal weeks, and synapsin I levels rose steadily during the same period. Primary reaggregate cultures containing cells from the caudate-putamen expressed DARPP-32 with a time course similar to that seen in vivo. The level of expression was not altered by coculturing with dopaminergic neurons from the rostral mesencephalic tegmentum. Thus, the postnatal increase in DARPP-32 levels in the caudate-putamen appears to be independent of transsynaptic or end-organ influences from the substantia nigra.     

Development of spontaneous neuronal activity in the caudate nucleus, globus pallidus-entopeduncular nucleus, and substantia nigra of the cat

Spontaneous single unit activity was obtained from caudate (Cd), globus pallidus-entopeduncular nucleus (GP-Ento), and substantia nigra (SN) neurons in kittens of 1-60 days of age and adult cats. Five developmental trends were found in the spontaneous firing patterns of these neurons: (1) overall mean interspike intervals (ISIs) decreased with age; (2) the occurrence of neurons with shorter mean ISIs (less than 400 ms) increased with age; (3) the occurrence of neurons with burst activity increased with age; (4) burst activity became more complex with age; and (5) the rate of burst occurrence in neurons with burst activity increased with age. Neurons within each region of the basal ganglia had characteristic patterns of spontaneous activity. Furthermore, the developmental patterns of spontaneous neuronal activity were different in each structure. The spontaneous activity of GP-Ento and SN neurons matured before the spontaneous activity of Cd neurons. Thus, spontaneous firing may mature in the output nuclei of the basal ganglia prior to its maturation in the Cd.     

Monoamine release from dopamine-depleted rat caudate nucleus reinnervated by substantia nigra transplants: An in vivo electrochemical study

Previous studies have shown that fetal substantia nigra (SN) transplanted into a cavity overlying a dopamine (DA)-denervated caudate nucleus can reverse a number of the behavioral abnormalities induced by the denervation. While some histochemical and physiological evidence suggests that this reversal is the result of a functional DA input from the transplant to the host brain, there is little direct evidence for transmitter release from ingrowing graft-derived nerve fibers. In the present work in vivo electrochemistry was used to analyse the magnitude, time course and spatial distribution of neurotransmitter releases evoked by local application of potassium (K+) from DA-depleted, SN transplant-reinnervated striatum. Animals were injected unilaterally with 6-hydroxydopamine (6-OHDA) into the SN and screened by measuring apomorphine-induced rotation. Some were then given SN grafts, which were placed in a 'delayed cavity' just dorsal to the lesioned striatum. Nafion-coated graphite epoxy capillary (GEC) electrodes were employed for the electrochemistry to minimize signals derived from ascorbate or acidic DA metabolites. The GEC electrode was fixed to a K+-filled micropipette and this assembly was used to map the caudate nucleus of control, 6-OHDA-treated, and 6-OHDA-treated, grafted animals. The morphometric relationships between striatal recording sites and transplant location were subsequently verified histologically. Releases from striatal sites within 1.0 mm of the SN grafts were slightly, but not significantly, less than those obtained from control caudate.(ABSTRACT TRUNCATED AT 250 WORDS)     

Motor responses induced by stimulation of the substantia nigra

Stimulating electrodes were stereotaxically implanted in the substantia nigra of adult cats. After recovery from surgery, stimulation with constant current square-wave pulses produced motor behavior similar to that obtained upon activation of striatal structures. The initial response was an “arrest” reaction, which subsequently involved head turning and finally contraversive circling movements as the frequency of stimulation was increased. All of these stimulus-induced responses were antagonized by either haloperidol or chlorpromazine. It is suggested that these behavioral responses are ultimately mediated by the reticulospinal system.     

Selective blockade by scopolamine of synaptic responses in cat's caudate nucleus and its modification by lesions of the substantia nigra.

Because it is commonly believed that acetylcholine is a synaptic transmitter in the caudate nucleus and that the reduction of striatal biogenic amines in Parkinson's disease leads to acetylcholine supersensitivity in the caudate nucleus, we investigated the effects of the muscarinic blocking agent scopolamine on synaptic responses of neurons in the intact feline caudate nucleus and in the caudate nucleus depleted of dopamine by long-standing nigrostriatal lesions. In the intact caudate nucleus, micro-iontophoretic application of scopolamine selectively blocked the neuronal responses to stimulation of the caudate nucleus near the recording site without affecting the responses to stimulation of the sensorimotor cortex or the substantia nigra in the same fashion. This suggests that acetylcholine is a synaptic transmitter of caudate interneurons. Responses to thalamic stimuli were also blocked by scopolamine, suggesting that acetylcholine may be a transmitter of thalamic afferents although the course of these afferents is unclear. In the dopamine-depleted caudate nucleus scopolamine was more effective than in the intact caudate nucleus blocking the neuronal responses to stimulation of the caudate nucleus. This greater blocking effect by scopolamine suggests an increased effect of endogenous acetylcholine in this response and supports previous observations of an increased excitatory effect of iontophoretic acetylcholine in the dopamine-depleted caudate nucleus. These results suggest that the acetylcholine supersensitivity which follows nigrostriatal degeneration may be due to increased effectiveness of synaptic transmission by cholinergic interneurons in the caudate nucleus.     

Complex EPSCs evoked in substantia nigra reticulata neurons are disrupted by repetitive stimulation of the subthalamic nucleus

Although substantia nigra reticulata (SNR) neurons fire bursts of action potentials during normal movement, excessive burst firing correlates with symptoms of Parkinson's disease. A major excitatory output from the subthalamic nucleus (STN) to the SNR is thought to provide the synaptic impetus for burst firing in SNR neurons. Using patch pipettes to record from SNR neurons in rat brain slices, we found that a single electrical stimulus delivered to the STN evokes a burst of action potentials. Under voltage-clamp conditions, STN stimulation evokes a complex EPSC that is comprised of an initial monosynaptic EPSC followed by a series of late EPSCs superimposed on a long-lasting inward current. Using varied stimulation frequencies, we found that the initial EPSC was significantly reduced or abolished after 2 s of 50-100 Hz STN stimulation. However, only 4 s of 1 Hz stimulation was required to abolish the late component of the complex EPSC. We suggest that differential effects of repetitive STN stimulation on early and late components of complex EPSCs may help explain the frequency-dependent effects of deep brain stimulation of the STN that is used in the treatment of Parkinson's disease.     

Monoamine effects on neuronal recovery cycles in globus pallidus,caudate nucleus,and substantia nigra

Summary In freely moving rats, averaged evoked potentials (AAER) to paired click stimuli delivered at varying interstimulus intervals were recorded with semi-microelectrodes simultaneously in globus pallidus (GP), caudate nucleus (CN), and substantia nigra (SN). The effects of intrapentoneal injection of reserpine and L-Dopa on the neuronal recovery cycles were studied. The results indicate that these drugs have different effects in the various structures. The major difference is a lack of effect in SN in contrast to substantial effects in GP and CN. This finding is compatible with the hypothesis that monoamines may be synthesized in SN but exert their major pharmacological action in the GP and CN.Supported, in part, by USPHS Grants NS 05184 and NS 2552, and The Eli Lilly Company.With 2 Figures     

Intracellular responses of caudate neurons to stimulation of cortex and substantia nigra following large thalamic lesions

The contribution of thalamic pathways to caudate intracellular responses evoked by cortical and nigral stimulation was assessed in 5 cats. No changes were found in either the excitatory or inhibitory components of these responses as a consequence of thalamic destruction. This result, together with other data from this laboratory, suggest thatindirect thalamo-striatal or cortico-striatal pathways are not required for mediating the observed striatal responses.     

高频电刺激丘脑底核对黑质神经元保护作用的研究

目的探讨高频电刺激丘脑底核对帕金森病(PD)大鼠黑质致密部(SNc)神经元的保护作用及机制。方法将40只SD大鼠随机分为3组,正常对照组10只,模型组及刺激组各15只。模型组及刺激组大鼠于脑内侧前脑束注射6-羟基多巴胺(6-OHDA)制备大鼠偏侧PD模型,刺激组大鼠丘脑底核区植入刺激电极实施高频电刺激(130Hz),对三组动物的行为学、SNc神经元的形态学改变进行观察和分析。结果术后2、4周时,刺激组SNc神经元凋亡的阳性率分别为(39.98±12.11)%和(41.12±9.23)%,模型组则为(61.74±7.82)%和(67.12±10.23)%;两组比较,差异有统计学意义(P<0.05)。术后2、4周时,刺激组Bcl-2/Bax比值为0.84±1.01和0.88±0.81,模型组则为0.39±0.15和0.30±0.58;两组比较,差异有统计学意义(P<0.05)。结论高频刺激丘脑底核对PD大鼠黑质SNc神经元有保护作用,其机制可能与改变了SNc区神经递质的分布和代谢有关。     

Control of substantia nigra pars reticulata neurons by the nucleus accumbens

In alpha-chloralose anesthetized, immobilized and ventilated cats stimulation of the nucleus accumbens (NA) evokes either inhibition or brief excitation followed by inhibition of extracellularly recorded spontaneously active or sural driven units in substantia nigra pars reticulata (SNpr). Inhibition peaked 50-80 msec following the onset of NA stimulation and persisted for about 300 msec. Pharmacologic interventions designed to characterize this inhibition were performed. Bicuculline, 0.01 to 0.1 mg/kg IV, consistently antagonized NA elicited suppression of SNpr cells. Diazepam 0.5 mg/kg effectively reversed bicuculline actions. Inhibition of spontaneously active units as well as sural excited units was blocked by bicuculline. Strychnine 0.1 to 0.5 mg/kg IV failed to affect inhibition arising from NA. These data suggest that, analogous to the GABAergic striatonigral pathway, inhibition of SNpr cells arising from NA utilizes GABA as a transmitter.