Modelling of the parkinsonian syndrome by the administration of kainic acid into the caudate nucleus

The experiments on rats have shown that bilateral administration of kainic acid (0.1-0.15 microgram) into the rostral parts of caudate nuclei led to the development of hypokinesia and rigidity. An increase in the electrical activity--the formation of the generator of pathologically increased excitement (GPIE) was noted in a zone of kainic acid injection. Rigidity and hypokinesia were attenuated and the GPIE activity was depressed after cyclodol (1-10 mg/kg) or L-DOPA (100-200 mg/kg) administration. Combined administration of cyclodol (2 mg/kg) and L-DOPA (50 mg/kg) induced potentiated antiparkinsonian effect. Dopamine microinjections into the GPIE area depressed its activity and abolished rigidity and hypokinesia. These data suggest that the Parkinson syndrome develops under the influence of GPIE induced by kainic acid administration into caudate nuclei.     

The effect of caudate nucleus stimulation on phenamine stereotypy in cats]

Large doses of d,1-amphetamine produce in cats a stereotype behaviour: its chronic administration results in low variability of the behaviour of one and the same animal and a stable set of motor automatisms. This makes it possible to use the cyclography for an objective estimation of the d,1-amphetamine-induced stereotypy. Low-frequency stimulation of the caudate nucleus head weakens or completely blocks the sterotype movements when current intensity is subthreshold for behavioral arrest reaction. The pecularities of the caudate control its similarity to the action of haloperidol and the absence of influence of the stimulation of the capsula interna and some thalamic nuclei on the stereotypy lead to the assumption that it is due to the depression of the inhibitory function of the caudate nucleus brought about by the intensification of the nigro-striatal dopaminergic transmission.     

Behavioral and neurophysiological evidence for a facilatory interaction between co-existing transmitters: cholecystokinin and dopamine

Cholecystokinin (CCK) and dopamine (DA) co-exist in ventral tegmental neurons which project via the mesencephalic pathway to the nucleus accumbens of the rat. CCK and DA are located in separate neurons in the substantia nigra which projects via the nigrostriatal pathway to the caudate nucleus in the rat. The functional significance of this peptide-amine co-localization was investigated using behavioral and neurophysiological techniques. CCK injected directly into the nucleus accumbens potentiated apomorphine-induced stereotypy and dopamine-induced hyperlocomotion. CCK injected directly into the caudate nucleus had no effect on apomorphine-induced stereotypy or dopamine-induced hyperlocomotion CCK injected alone into either site did not induce stereotypy or hyperlocomotion. The dose-response curve to apomorphine induction of stereotypy was shifted to the left by CCK, indicating increased sensitivity to the dopaminergic agonist. Neurophysiological analysis of the firing rate of ventral tegmental neurons demonstrated that CCK produced a left-shift in the dose-response curve of apomorphine on inhibition of neuronal firing. These data suggest that CCK acts as a modulator of dopamine, increasing neuronal responses to dopaminergic agonists. The potentiation of dopamine by CCK may be specific to the mesolimbic neurons, where CCK and DA co-exist in the rat.     

Effect of clozapine on the behavioral and electrographic indices of the arrest function of the caudate nucleus in cats

In unrestrained cats clozapine in increasing doses (1--5 mg/kg) caused a behavioural depression and suppression of amphetamine-induced stereotypy of behaviour against the background of marked vegetative shifts. Similarly to chlorpromazine clozapine intensified the behavioural arrest reaction) and electrographic (neocortical caudate spindle) indices of the arrest function of the caudate nucleus. Arrest reaction changed more distinctly in stimulation of the ventral parts of the head of the nucleus. Clozapine also eliminated the weakening of the caudate responses caused by the stereotypical doses of amphetamine.     

Alterations in amphetamine stereotypy following acute lesions of substantia nigra

Stereotypy induced by high doses of amphetamine has been related to the ability of this drug to increase the release of dopamine in the caudate nucleus and to block its reuptake. Since amphetamine-stimulated dopamine release in the caudate is blocked by acute lesions of the nigrostriatal pathway, the mechanism by which amphetamine acts to produce stereotypy may be dependent upon intact nigrostriatal impulse flow. The present study examined the involvement of nigrostriatal impulse flow in amphetamine stereotypy by determining the effect of acute, bilateral lesions of substantia nigra pars compacta on measures of stimulant-induced stereotypy and motility. Acute nigral lesions did not significantly alter the stereotypy or motility induced by 3.0 or 6.0 mg/kg amphetamine. These results suggest that the observed behavioral effects of amphetamine do not require an intact nigrostriatal pathway, and thus may involve changes in spontaneous release or reuptake of dopamine rather than in changes in impulse-coupled dopamine release.     

Structural-functional connections of the lemniscus system with the caudate nucleus in the cat

Afferent projections were studied of nuclei of the spinal cord dorsal columns to the caudate nuclei. Evoked potentials (EPs) were recorded in the caudate nuclei and the nuclei of dorsal columns of the spinal cord to stimulation of the forelimb against the background and after unilateral elimination of the medial lemniscus. After the section, the EPs in the recorded nuclei sharply intensified in response to stimulation of the forelimb, ipsilateral to the section. Degenerative changes were also shown by electron microscopy in axonal terminals in the caudate nuclei at the operated side. Conclusion is drawn that the caudate nuclei receive direct connections from the contralateral nuclei of the spinal cord dorsal columns, which probably, conduct mainly kinesthetic afferent influences.     

In vivo stereological assessment of caudate volume in man: effect of normal aging

Using intermediate weighted magnetic resonance imaging (MRI) and a systematic sampling stereological method in 39 normal volunteers aged 24-79 years old, we demonstrated a marked age-associated decline in caudate nuclei volume (r = -0.69, p less than 0.0001). The mean absolute volume of the caudate nuclei in this study (9.4 cm3) was almost identical to that reported in a previous autopsy study and further confirms the validity of this stereological technique for use with MR images. This technique will provide a method for measuring the caudate and other nuclei in vivo, from brain images and, as such, a research tool to correlate age-associated changes in cognitive, sensory and motor function with caudate nucleus volume and other brain regions.     

Dynamics of caudate nucleus involvement in the process of internal inhibition of the food-getting reflex]

Changes of slow spindle electrical activity (12 to 14 cps) and evoked potentials in the cat caudate nuclei and the motor cortex were studied at different stages of elaboration of differentiation inhibition of a conditioned food-procuring reflex to acoustic stimuli. It has been shown that participation of the caudate nuclei in the inhibitory process begins at the stage of enhancement of food-procuring activity (second stage) and is apparently due to the animal's strong alimentary motivational excitation. At the third stage the inhibitory influence of caudate nuclei on the animal's motor activity in general, and the activity of the motor cortex in particular, develops to the full.     

Role of the caudate nucleus in the development of evoked synchronized activity

Synchronized activity (spindles, augmentation response) evoked by stimulation of thalamic nonspecific, association, and specific nuclei was investigated in chronic experiments on 11 cats before and after successive destruction of the caudate nuclei. After destruction of the caudate nuclei the duration of spindle activity in the frontal cortex and subcortical formations (thalamic nuclei, globus pallidus, putamen) was reduced to only three or four oscillations. In the subcortical nuclei its amplitude fell significantly (by 50±10%); in the cortex the decrease in amplitude was smaller and in some cases was not significant. Different changes were observed in the amplitude of the augmentation response, depending on where it was recorded. In the subcortical formations it was considerably and persistently reduced (by 50±10%); in the cortex these changes were unstable in character. Unilateral destruction of the caudate nucleus inhibited synchronized activity evoked by stimulation of the thalamic nuclei on the side of the operation only. Destruction of the basal ganglia (caudate nucleus, globus pallidus, entopeduncular nucleus, and putamen) did not prevent the appearance of synchronized activity; just as after isolated destruction of the caudate nucleus, after this operation synchronized activity was simply reduced in duration and amplitude. It is suggested that the caudate nucleus exerts an ipsilateral facilitatory influence on the nonspecific system of the thalamus during the development of evoked synchronized activity.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 9, No. 3, pp. 239–248, May–June, 1977.     

Appearance of parkinsonian syndrome after administration of delta sleep-inducing peptide into the rat substantia nigra

Bilateral microinjection of delta-sleep-inducing peptide (DSIP) (10.0 nmol) into the substantia nigra provoked hypokinesia and rigidity in rats observed during 4.0 hours. Injection of DSIP in dose of 5.0 nmol into the substantia nigra or into the nuclei caudati in dose of 10.0 nmol did not induce such symptoms. The enhanced slow-wave activity was recorded in caudate nuclei during hypokinesia and rigidity which demonstrated the formation of the generator of pathologically enhanced excitation (GPEE). The systemically cyclodol administration resulted in abolishment of rigidity and increase in locomotor activity. The conclusion is that bilateral intranigral DSIP injection caused acute parkinson syndrome in rats due to the formation of cholinergic GPEE in caudate nuclei. The hyperactive caudate nuclei act as the pathologic determinant which induces the parkinson syndrome.     

Change in phenamine stereotypy in cats after the electrical stimulation of the caudate nucleus

Two types of behavioral shifts occur in cats after cessation of repeated low-frequency stimulation of the caudate nucleus head. Behavioral depression originates more frequently from the dorsomedial part of the head whereas stimulation of the ventrolateral part induces the activation before depression. The number and pattern of stereotype movements are variously changed against the background of these shifts following administration of the minimal effective phenamine dose. Desorganization takes place after stimulation of the dorso-medial nucleus parts followed by stereotypy reduction or, on the contrary, by its enhancement in combination with caudate activation.     

Pentylenetetrazol (PTZ)-kindling development in intact and subcortical structure lesioned rats

Kindling was induced in male wistar rats (280-320 g) by daily ip injections of PTZ in subthreshold doses (30 mg/kg). Repeated administration of PTZ to animals resulted in developing of enhanced seizures and also enhanced seizure susceptibility which could be sustained for a long time (6 months) after last seizure paroxysm. The lesioned hippocampus retarded the manifestation of PTZ kindling, where as lesioned caudate nuclei increased the seizure kindling development. Results also revealed hippocampus as a determinant structure in PTZ kindling formation, which stabilize the epileptic manifestations and make them chronic, at the same time caudate nuclei retarded the epileptic seizures stabilization. This role may be only antiepileptic, and not anti-kindling as is known for caudate nuclei.     

In vivo release of transmitters in the cat basal ganglia

The release of transmitters was studied in various structures of the basal ganglia in cats implanted with several push-pull cannulas. Local depolarization enhanced Met-enkephalin release in the globus pallidus. Activation of striatonigral substance P(SP) neutrons stimulated the transmitter release from terminals. Unilateral electrical stimulation of the caudate nucleus evoked GABA release in both substantia nigrae and pallidoentopeduncular nuclei. The unilateral facilitation or interruption of nigral SP transmission modified dopamine (DA) release in the ipsilateral caudate nucleus in contrast, modifications of GABAergic or glycinergic nigral transmissions induced bilateral symmetrical effects, whereas bilateral asymmetrical changes in DA release in the two caudate nuclei were seen during the unilateral modification of nigral DA transmission. Changes in the dendritic release of DA induced changes in serotonin release both in the substantia nigra and in the ipsilateral caudate nucleus. Finally, it will be shown that acetylcholinesterase can be released from the substantia nigra and the caudate nucleus through processes dependent on nerve activity.     

Seasonal changes in song nuclei and song behavior in Gambel's white-crowned sparrows

In males of several songbird species, the morphology of forebrain nuclei that control song changes seasonally. The only seasonally breeding songbird in which seasonal changes in the structure of song control nuclei have been reported not to occur is the nonmigratory Nuttall's subspecies of white-crowned sparrow. In the present study, we manipulated photoperiod and plasma testosterone concentrations in captive male white-crowned sparrows of the migratory Gambel's subspeices. Males exposed to photoperiods and plasma testosterone concentrations typical of those experienced by wild breeding males had larger song control nuclei than males held on a winter photoperiod. We also found seasonal change in stereotypy of spectral and temporal parameters of song in wild Gambel's white-crowned sparrows. We hypothesize that seasonal changes in song control nuclei may correlate with seasonal changes in song stereotypy. © 1995 John Wiley & Sons, Inc.     

Role of intralaminar thalamic nuclei in strengthening inhibition induced by stimulation of the caudate nucleus

The influence of preliminary subthreshold activation of thalamic intralaminary nuclei on achievement of instrumental reflex and on inhibitory effects, caused by stimulation of the caudate nucleus head, were studied in chronic experiments on 5 dogs with a model of instrumental defensive conditioned reflexes, providing for maintainance of a given posture. It was shown that the preceding high-frequency electrostimulation of intralaminary nuclei activates motor components of the instrumental response (shortened latency, EMG and mechanogram of the response, increased amplitude of instrumental response) and significantly lowers threshold strength of the current, necessary for obtaining "caudate pause". The greatest increase in inhibitory influences, caused by stimulation of the caudate nucleus head, was observed when thalamic stimulation preceded stimulations, localized in the dorsolateral segment of the caudate nucleus head. The obtained data are discussed in aspect of Buchwald et al. hypothesis on the existence of "caudate loop".     

Evidence for a Selective Localization of Voltage-Sensitive Ca2+ Channels in Nerve Cell Bodies of Corpus Striatum

Specific binding sites for [3H]nitrendipine, an organic Ca2+ channel antagonist, were abolished in crude synaptosomal membranes of kainic acid-lesioned caudate nuclei. In contrast, specific lesions of dopaminergic or serotonergic axon terminals in caudate nuclei failed to alter the density or the affinity of [3H]nitrendipine binding sites. In addition, the basal and veratridine-stimulated 45Ca2+ accumulations were greatly impaired in slices prepared from kainic acid-lesioned caudate nuclei. The veratridine-elicited accumulation of 45Ca2+ in control slices was attenuated by addition of tetrodotoxin in the incubation medium. The present data provide evidence that most of the [3H]nitrendipine binding sites and the voltage-dependent Ca2+ channels are located in intrinsic neurons or interneurons in caudate nucleus. In contrast, destruction of dopaminergic or serotonergic nerve terminals emanating from other brain areas and innervating the caudate nucleus failed to change the apparent Bmax value for [3H]nitrendipine binding.     

Parkinson syndrome after administration of acetylcholine into the caudate nuclei

Rats with the Parkinsonian syndrome induced by administration of acetyl choline and proserine into the rostral part of both caudate nuclei manifest an increased electrical activity (EA) in this part. Tremor, oligokinesia and rigidity are characterized by the appearance of paroxysmal EA with high amplitude of slow and rapid waves. The data obtained allow to conclude that neuropathophysiological basis of the Parkinsonian syndrome is the formation of the generator of pathologically enhanced excitation (GPEE) in the caudate nuclei. Some peculiarities of the GPEE activity in tremor and akinetic rigidity syndromes were observed. Intrarostral administration of dopamine or intraperitoneal administration of cyclodol resulted in the inhibition of GPEE and disappearance of clinical manifestations of Parkinsonian syndrome.     

Correlation of behavioral and neurochemical effects of acute administration of cocaine in rats.

Effects of cocaine were investigated on spontaneous motor activity (SMA) and stereotypy as well as on the concentrations of norepinephrine (NE), dopamine (DA), serotonin (5-HT) and acetylcholine (ACh) in the discrete brain areas, such as the caudate nucleus (CN), diencephalon-midbrain (DM) and pons-medulla (PM) in rats up to 90–120 min following its injection in single doses (15–20 mg/kg, i.p.). After cocaine administration, the SMA was increased usually reaching its peak between 10–20 min, and then decreased gradually. Stereotypy and its components gradually increased to their maximum at about 50–60 min and remained at that level during rest of 120 min sessions. NE levels slightly increased in the DM and PM at 10 min post-drug after which they were decreased at 20 min. DA levels in the CN and DM were increased markedly at 20 min post-drug and decreased at 40 min. 5-HT levels in DM and PM decreased gradually up to 20 min, then began to increase. ACh level in the CN was gradually increased at 40 min and then decreased. It appears that cocaine-induced hyperactivity and stereotypy followed release of NE and DA after their accumulation in the respective brain areas.     

Striatal input from the ventrobasal complex of the rat thalamus

We have analyzed whether caudal regions of the caudate putamen receive direct projections from thalamic sensory relay nuclei such as the ventrobasal complex. To this aim, the delivery of the retrograde neuroanatomical tracer Fluoro-Gold into the caudal caudate putamen resulted in the appearance of retrogradely labeled neurons in the ventral posteromedial and ventral posterolateral thalamic nuclei. These projections were further confirmed with injections of the anterograde tracers biotinylated dextran amine or Phaseolus vulgaris leucoagglutinin into these thalamic nuclei, by showing the existence of axonal terminal fields located in the caudal striatum. These results support the existence of direct projections linking the thalamic ventrobasal complex and the caudal striatum in the rat, probably via collateralization of thalamocortical axons when passing through the caudate putamen, and therefore supporting the putative involvement of the caudal striatum in sensory-related functions.     

Relationship between neurophysiological indices of cognitive processes and MRI characteristics of some brain structures in healthy subjects and patients with schizophrenia

The relationships between the parameters of waves of auditory event-related potentials (ERPs) in the oddball paradigm and the volumes of the hippocampus, amygdala, and caudate nuclei were analyzed in healthy subjects and patients with schizophrenia. The data obtained suggest that faster mental processes and stronger activation and/or synchronization of the activity of ERP wave generators in healthy subjects correspond to smaller volumes of the structures studied. The structure of the relationships in patients with schizophrenia differed from the normal one; significant correlations were observed with the volume of the caudate nuclei, and more pronounced “normalization” of neurophysiological characteristics was associated with large volumes of these structures.