Stimulation Of Substantia Nigra Research Articles

Intracellular analysis of the development of responses of caudate neurons to stimulation of cortex, thalamus and substantia nigra in the kitten

Intracellular recordings were made from caudate neurons in anesthetized kittens of 2–72 days of age. In adult cats, results of intracellular recordings indicate that caudate neurons respond most frequently to stimulation of their major afferents from cortex, thalamus and substantia nigra with a sequence of excitation followed by inhibition (EPSP-IPSP sequence). The results of the present study show that the prominent IPSP of this sequence is not well developed in young kittens and does not reach adult values in terms of frequency of occurrence until beyond 40 days of age. Amplitude and duration of the IPSP evoked by cortical stimulation also did not reach adult values until beyond 40 days of age. In contrast, EPSPs can be evoked in the youngest kittens by stimulation of afferents to the caudate. These findings suggest that the caudate nucleus may alter its role during development. In early postnatal periods it functions as a simple relay system transmitting incoming information to its outputs in a relatively unaltered fashion. Later in development it becomes a system capable of complex modulation and filtering of neural information.

An electrophysiological study of thalamo-caudate neurones in the cat.

Thalamo-caudate projection neurones were identified in cats by antidromic activation from the caudate nucleus, under chloralose anaesthesia or in cerveau isolé preparations. Units in nuclei centralis lateralis, medialis dorsalis, and centrum medianum-parafascicularis responded antidromically to one or more electrodes of a caudate nucleus array at latencies ranging from 0.4 to 16 ms. The responses did not appear to result from stimulus spread to the internal capsule. A separate population of medial thalamic units responded postsynaptically to caudate stimulation, at modal latency exceeding modal antidromic latency by 2 ms. Comparison of apparent conduction velocities for each thalamic nucleus indicated that the postsynaptic responses were activated by collaterals of thalamo-caudate neurones. A proportion of thalamo-caudate neurones responded to somatic stimulation; some of these were inhibited by caudate stimulation, and a few discharged on substantia nigra stimulation. These results demonstrate the possibility of somatic afferent and nigrofugal inputs to the caudate nucleus mediated by neurones of the medial thalamus.

Influence of electrical stimulation of the substantia nigra on spontaneous activity of raphe neurons in the anesthetized rat

Recent studies of afferent connections of the anterior raphe using the horseradish peroxidase technique have demonstrated a major projection originating in the substantia nigra (SN). The present acute electrophysiological study examined the influence of stimulation of this afferent on the activity of individual neurons in the raphe of the posterior midbrain and anterior pons ( n=51), and of a control group of cells ( n=15) located 2 mm lateral to the raphe. The predominant effect of SN stimulation at 0.1–1.0 mA, 1 Hz or 10 Hz, was suppression of raphe activity, with 63% of the cells showing cessation of firing following SN pulses and only 8% showing excitation. The average duration of suppression was 200 msec at 1 Hz and 38 msec at 10 Hz. In contrast, 40% of the lateral cells were excited, with 27% of the cells showing suppression. The mean duration of total suppression of lateral cell firing was 61 and 17 msec at 1 and 10 Hz, respectively. The results from the raphe cells are consistent with recent reports of stimulation of other forebrain and brainstem afferents to the raphe in which suppression of raphe activity was the main effect.

Responses of cat cerebellar cortical 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.

Electrophysiological study of the nigro-tectal pathway in the rat

The effects of substantia nigra (SN) stimulation to the activity of the ipsilateral superior colliculus (SC) have been studied in the rat. Two types of responses were observed: pure inhibitions or excitation sometimes followed by an inhibitory period. The comparison between the latency of these various orthodromic responses and the conduction time of the nigro-tectal fibers, as determined by antidromic activation, led us to conclude that there is a possible inhibitory function of the nigro vectal pathway. The problem of coactivation of pedunculus cerebri (Ped) and tractus opticus (To) fibers is discussed.

The effect of substantia nigra stimulation and morphine on α-motoneurones and the tail-flick response

Rats were used to study the effect of unilateral stimulation of the substantia nigra on the reflex discharge of α-motoneurones and on the reaction time of the tail-flick response. In preparations with prenigral decerebration, nigral stimulation facilitated monosynaptic α-reflex activity ehilst γ-reflex activity remained unchanged. The facilitation of monosynaptic α-reflex activity was reduced by naloxone (1 mg/kg); morphine (2 mg/kg) did not change the number of α-reflex discharges, but it reduced the α-reflex latency, enhanced the effect of nigral stimulation on the latency and abolished the effect of naloxone on nigral facilatation. Nigral stimulation prolonged the reaction time of the tail-flick response in rats with an intact brain and after prenigral decerebration. Naloxone did not influence the anti-nociceptive effect of nigral stimulation, whilst morphine enhanced it in rats with an intact brain. The anti-nociceptive effect exerted by morphine in animals with an intact brain was abolished by prenigral decerebration, and an additional spinalization restored it. Inactivating the nigral neurones by unilateral microinjections of procaine or GABA into the substantia nigra depressed the nociceptive reflex. It is concluded that (1) activation of nigral neurones influenced mono- and polysynaptic reflexes in a reciprocal fashion by a pathway descending via brain stem relays to the spinal cord, (2) inactivation of nigral neurones produced similar changes in reflex activity by altering the function of the nigro-striatal feedback system, the outlet from the system to the spinal cord not being the substantia nigra, (3) morphine influenced the nociceptive reflex by an action at different levels of the central nervous system.

Neuropharmacological studies on the nigro-striatal and raphe-striatal system in the rat

The responses of single neostriatal neurones to substantia nigra (SN) and dorsal raphe nucleus (DRN) stimulation and iontophoretic administration of several drugs were studied in urethane-anaesthetised rats. Stimulation of the SN-evoked excitation followed by inhibition in striatal neurones. In some cells only inhibition of firing was evoked indicating that there may be separate nigrostriatal inhibitory and excitatory pathways. DRN stimulation evoked mainly inhibition of striatal cell firing. The activity of most neurones responding to SN and DRN stimulation was depressed by iontophoretically administered dopamine, 5-hydroxytryptamine and GABA and increased by acetycholine. Studies with antagonist revealed that α-flupenthixol reduced responses to dopamine and 5-hydroxytryptamine and inhibition evoked by SN and DRN stimulation. Bicuculline methochloride only reduced responses to GABA. Methysergide selectively reduced responses to 5-hydroxytrptamine and also reduced DRN- but not SN-evoked inhibition. It was concluded that the SN-evoked inhibition was probably mediated by dopamine and DRN-evoked inhibition by 5-hydroxytryptamine.

Effects of post-trial reinforcing vs. subreinforcing stimulation of the substantia nigra on passive avoidance learning

STAUBLI, U. AND J. P. HUSTON. Effects of post-trial reinforcing vs. subreinforcing stimulation of the substantia nigra on passive avoidance learning. BRAIN RES. BULL. 3(5) 519–524, 1978.—Experiments were designed to investigate the role of post-trial reinforcing and subreinforcing stimulation of the substantia nigra on memory processing. Thirty sec post-trial reinforcing stimulation (0.2 sec on/1.8 sec off) impaired learning of response suppression in a step-down task compared to control animals as well as to animals stimulated at subthreshold current level (i.e., at 25% of the current level shown to maintain optimal self-stimulation in previously performed self-stimulation sessions). In a second small-box passive avoidance experiment, i.e., the alcove-avoidance task, opposite results were attained: Subreinforcing stimulation attenuated learning whereas neither suprathreshold stimulated animals nor control animals showed impairment of learning. The conclusions drawn from these results are as follows: Post-trial stimulation of the substantia nigra interferes with memory processing. This attenuation of learning is obviously task-dependent and can additionally be influenced by the quality of the stimulation, i.e., whether it is reinforcing or not. Possible explanations to account for these task-dependent and quality of stimulation-dependent effects of post-trial substantia nigra stimulation are discussed.

Effect of substantia nigra stimulation on identified neurons in the VL-VA thalamic complex: Comparison between intact and chronically decorticated cats

The effects of substantia nigra (SN) stimulation on the activity of the nucleus ventralis lateralis of the thalamus (VL) have been studied. The VL cells were identified as relay or non-relay cells among the cerebellothalamocortical pathway on the basis of orthodromical activation from the cerebellum and antidromical activation from the cortex. Certaiin experiments were performed after wide pericruciate decortication in order to eliminate the response due to unavoidable activation of corticofugal fibers. These results show that nigrothalamic neurons exert an inhibitory effect on VL cells. This inhibition was observed on the relay as well as on non-relay cells and was strong enough to suppress the cerebellar monosynaptic excitatory input. Thus the SN can moduulate the information running along the cerebellothalamocortical pathway. The topographic localization of inhibited cells suggests that the SN controls the activity of the thalamic neurons which interfere with axial and proximal musculature.

Movement induced in cataleptic rats: Differential effects produced by electrical stimulation of the lateral hypothalamus, substantia nigra, and reticular formation

Haloperidol catalepsy can be countered by electrical stimulation of the lateral hypothalamus (LH) and, to a lesser extent, the reticular formation (RH). Substantia nigra (SN) stimulation proved to be least effective in this regard. Dissociation between behavioral arousal and cortical EEG during stimulation of the RF in cataleptic rats was observed.

Dual excitatory inputs to caudate spiny neurons from substantia nigra stimulation

In the present set of experiments of two component excitatory postsynaptic potential (EPSP) (fast and slow) was recorded from caudate (Cd) neurons after substantia nigra (SN) stimulation in the alpha-chloralose anesthetized cat. Several unique properties of the fast response are demonstrated and used to determine certain functional properties of Cd neurons. The following conclusions have been drawn from these experiments. (1) A dual excitatory innervation pattern (fast and slow) exists to the Cd from SN stimulation. (2) The fast system is independent of the Cd efferent system. (3) Neurons receiving this dual input are spine laden neurons. (4) Dendritic inhibition is operating on these neurons and often has little or no direct influence on the observed soma membrane potential. The dendritic inhibition reduced test EPSP amplitude for several hundred milliseconds for all Cd afferents except for the fast SN input. Such a decoupling of the fast input from the inhibition may play an important role in Cd signal processing.

Differential morphine effects on evoked impulse activity in the caudate and central grey

This study had two primary objectives: 1. (1) to develop a new physiological method for investigating opiate action, based on the effect of morphine on evoked impulse activity in small neuronal populations, and 2. (2) to test the hypothesis that morphine's effects would vary with response site (caudate and central grey), and with stimulation site (sciatic nerve, substantia nigra). Bipolar recordings were made from curarized, artificially respired rats. Morphine increased stimulus thresholds for sciatic evoked responses in both brain areas, with especially marked effects in the central grey. Sciatic stimulation produced phasic (transient) responses in both brain areas to mild stimulation and tonic (sustained) responses to more intense stimulation; the tonic responses were depressed more effectively than phasic responses. Substantia nigra stimulation produced only tonic responses in both areas, and morphine did not alter these stimulation thresholds. Morphine effects were blocked and reversed by naloxone. Thus, clear differential depressive effects of morphine were demonstrated in terms of function (phasic vs. tonic responses), in terms of stimulus site, and in terms of responding site.

Convergence of excitatory synaptic inputs to caudate spiny neurons

Intracellular recordings were obtained from cat caudate nucleus neurons. These cells responded with convergent, monosynaptic EPSPs to cerebral cortex, intralaminar thalamus, and substantia nigra stimulation. Intracellular injection of horseradish peroxidase into these electrophysiologically defined neurons shows that they represent the spiny neuron of the caudate based upon somadendritic morphology. The axons of these cells are appreciably longer than previous reports indicate. Several lines of evidence are discussed to question the intrinsic nature of these neurons.

Effects of Electrical Stimulation of the Substantia Nigra on Responses of the Lateral Geniculate Body Neurons to Light

Effects of electrical stimulation of substantia nigra on responses of the lateral geniculate neurons to light were studied. Responses of the neurons to flash were enhanced or inhibited by conditioning stimulation of the substantia nigra. Enhancement of firing by nigral stimulation more often occurred in neurons excited primarily by flash, but inhibition was more commonly observed in those which showed a primary neuronal silence after light.

Alteration of basal ganglia evoked responses by reserpine and L-dopa.

The effects of reserpine and L-Dopa on basal ganglia evoked potentials were investigated in cats. The caudate response resulting from substantia nigra stimulation and the substantia nigra response elicited by globus pallidus stimulation were increased at several hours after the systemic administration of reserpine. L-Dopa in the presence of dopa decarboxylase inhibition (MK-486) depressed these responses and reversed the effect of reserpine at 0.5 h after administration. Reserpine did not reverse the L-Dopa effect. Reserpine and L-Dopa caused no significant change in responses between other basal ganglia structures. These data give evidence that the basal ganglia are major sites for reserpine and L-Dopa action.

Alterations in neostriatum tyrosine hydroxylase activity and behavior induced by electrical stimulation of the substantia nigra

Alterations in neostriatum tyrosine hydroxylase activity and behavior induced by electrical stimulation of the substantia nigra

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.

Electrophysiological properties of caudate neurons following substantia nigra, motor cortex, and amygdaloid nuclear complex stimulation of the rat.

Extracellular single unit activities were recorded from the caudate nucleus (CN) in rat anesthetized with urethane. The present study is related to a selected population of CN neurons, only cells that exhibited spontaneous activity being investigated. A wide range of spontaneous firing was observed (0.1–15 spikes/sec). The majority of the units responded to electrical stimulation of substantia nigra (SN), motor cortex (MC), and amygdaloid complex (Amyg), 72, 70 and 65%, respectively; both decreased and increased firing rates were obtained following the three central stimulations. The majority of the responsive neurons (87%) showed significant alteration of their spontaneous firing rates following each of the three stimuli applied, i.e., there was a high degree of convergence. If a cell responded to one particular stimulation by an increase in discharge rate, the same cell would not necessarily respond to the other two stimuli in the same direction of change. Time locked action potentials were observed only following Amyg stimulation in 32% of the CN neuronal population. In the present study the population of units which exhibit spontaneous activity demonstrate polysynaptic connections with MC and SN. The possibility of mono, oligo- and polysynaptic connections from Amyg to CN is discussed. It is suggested that the connection between Amyg and CN provides a route through which the limbic system may influence somatic motor activity.

Suppression of extralemniscal thalamic unit responses by substantia nigra stimulation

Suppression of extralemniscal thalamic unit responses by substantia nigra stimulation

Antagonism of dopamine-mediated inhibition in the nigro-striatal pathway: A mode of action of some catatonia-inducing drugs

Recordings were made from single neurones in the caudate nucleus of anaesthetised rats. Dopamine (DA) was applied by iontophoresis to these neurones and its effects compared with those of substantia nigra (SN) stimulation. There was a good correlation between the inhibitory effects of SN stimulation and inhibitory actions of DA. Papaverine and bulbocapnine applied iontophoretically or given intravenously blocked the inhibitory effects of SN stimulation and of DA. The results provide evidence supporting the view that dopamine is the transmitter for the nigro-striatal pathway mediating inhibition in the rat. It is suggested that blockade of this pathway is one of the mechanisms by which bulbocapnine and papaverine produce catatonia.