Fos and nitric oxide synthase in rat brain with chronic mesostriatal dopamine deficiency: effects of nitroglycerin and hypoxia.

We found sustained proto-oncogene c-fos expression in neurons of the lateral and medial neostriatum and suppression of this expression in nitric oxide synthase (NOS)-containing cells within the islands of Calleja after lesions of the dopaminergic mesostriatal system induced by 6-hydroxydopamine. Systemic administration of nitroglycerin (NTG) or mild hypoxia resulted in a decreased of c-fos expression in the dorsolateral part of the denervated neostriatum. However, in other brain structures NTG or mild hypoxia evoked sustained c-fos expression in NOS-containing neurons and in the sources catecholaminergic projections involved in the control of cardiovascular function. We propose that the administration of NTG, an NO donor, or hypoxia partially attenuate the consequences of an excessively increased glutamate level in the denervated neostriatum which are manifest in high level of c-fos expression.

Morphofunctional studies of the interactions of the glutamatergic, cholinergic, and dopaminergic systems in the neostriatum.

Morphological, electrophysiological, and behavioral experiments were used to study the interactions of the glutamatergic, cholinergic, and dopaminergic systems in the neostriatum of white rats with unilateral lesions of the mesostriatal dopaminergic system induced by 6-hydroxydopamine. The neostriatum was shown to contain both synaptic and interneuronal nonsynaptic interactions between these neurochemical systems. It is suggested that glutamate, which is present in excess in conditions of prolonged dopamine deficiency, has toxic effects on corticoneostriatal synaptic connections.

[Morpho-functional study of the glutamatergic, cholinergic, and dopaminergic systems interaction in the striatum]. / Morfofunktsional'noe issledovanie vzaimodeistviia glutamat-, kholin-, i dofaminergicheskoi sistem v neostriatume.

Interaction among glutamat-, cholin-, and dopaminergic systems in the neostriatum of white rats with unilateral local lesion of the mesostriatal dopaminergic system. Both synaptic and interneuronal non-synaptic interactions among the neurochemical systems under study, were revealed.

Reversible blockade, induced by the neurotoxin MPTP, of corticofugal impulse activity to neurons of the caudate nucleus in cats.

It has been demonstrated in acute experiments in cats anesthetized with nembutal and immobilized with ditilin [succinylcholine iodide--Translator] that the number of neurons of the caudate nucleus responding to a single stimulation of the motor cortex with action potentials with a latent period less than 8.0 msec in the first 10-12 days after a course of injections of MPTP (5 mg/kg daily for 5 days, intramuscularly) decreased significantly as compared with the control. Their number is gradually restored by the 45th-54th day after the administration of the neurotoxin. A one-time injection of the dopaminomimetic, apomorphine (5 mg/kg, intramuscularly), also significantly decreases the number of neurons with a latent period of the responses less than 8.0 msec for 5 h in the intact animals, and is incapable of removing the blockade of the corticoneostriatal impulse activity in animals with an MPTP-induced dopamine deficit. The hypothesis is advanced that dopamine exerts a protective inhibitory influence on the conduction of corticofugal glutamatergic impulse activity to neurons of the neostriatum.

[The reversibility of a blockade of corticofugal pulse trains to the neurons of the caudate nucleus in cats evoked by the neurotoxin MPTP]. / Ob obratimosti blokady kortikofugal'noi impul'satsii k neironam khvostatogo iadra u koshek, vyzvannoi neirotoksinom MFTP.

In anesthetised cats, the number of the caudate nucleus neurons responding to a cortical stimulation with latency less than 8.0 ms, increased within 10-12 days after the MPTP administration and then gradually recovers by the 45th-54th day after the neurotoxin administration. Dopamine seems to exert a protecting-inhibiting effect on transmission of corticofugal glutamatergic impulses travelling towards the neostriatum neurons.

Topographical organization of the sources of discrete cortical projections within the striatum as determined by a retrograde fluorescence tracing technique in the cat.

The projections from the neostriatum and the paleostriatum to the cerebral cortex in the cat were examined by means of retrogradely transported fluorescent tracers primuline, Fast Blue, Nuclear Yellow and Evans Blue injected into different neocortical fields. In all cases after dye injections only large labelled cells of sources of striatocortical ipsilateral projections were observed. The main projections from the caudate nucleus and the putamen are directed to the auditory and neighbouring "associative" cortex, and more numerous projections from the globus pallidus are addressed to the motor cortex. No sources of cortical projections within the entopeduncular nucleus were found. Simultaneous injections of Fast Blue and primuline into even closely located and tightly bound functional regions of parietal or temporal cortex failed to reveal double-labelled neurons in the caudate nucleus, internal capsule, putamen and globus pallidus. Thus, our findings on cats are consistent with recent studies on rats and monkeys that suggest that striatal neurons innervate relatively small, restricted fields of the neocortex. Again, the results show evidence for a significant contribution to cholinergic cortical innervation not only of magnocellular neurons of the basal forebrain but also of large neo- and paleostriatal cells.

A loss of short-latency excitatory caudate unitary responses to motor cortex but not to motor thalamic nuclei stimulation in MPTP-treated cats.

The effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 5 mg/kg i.m. for 5 days) on the evoked activity of caudate neurones were studied extracellularly in ketamine-anaesthetized and myorelaxant-immobilized cats. Two days after the last MPTP injection the latency of caudate neurone responses to the motor cortex stimulation increased as compared to intact animals, due to a 10-fold decrease in the number of neurones with short-latency responses (from 1.8 up to 8.0 ms). At the same time, no essential changes were observed under the influence of MPTP in the distribution pattern of the latency of caudate neurone responses to the stimulation of the ventral anterior and ventral lateral nuclei of the thalamus. The suggestion that dopamine protects monosynaptic transmission of impulses from the cerebral cortex to neostriatum neurones is discussed.

[Effect of damage of the nigro-neostriatal dopaminergic system by MPTP on the transmission of corticofugal impulses to the neurons of the caudate nucleus]. / Vliianie povrezhdeniia nigro-neostriatnoi dofaminergicheskoi sistemy neirotoksinom MFTP na peredachu kortikofuga'lnoi impu'lsatsii k neironam khvostatogo iadra.

It is shown in acute experiments on cats (males) that the induced responses as action potentials (AP) by the latent period (LP) less than 8.0 ms in the caudate nucleus neurons (CN) to a single stimulation of the motor zone of the cortex (MI) are more frequently inhibited than facilitated after specifying single stimulation of the compact part of the black substance (BS) in the intervals between stimuli 10-100 ms. As a result of system multiple injection of MPTP neurotoxin during 5 days per 5 mg/kg the number of CN neurons responding to stimulation of MI, AP, LP less than 8.0 Usec and to stimulation of BS-LP less than 10.0 ms reliably decreases. A conclusion is made that dopaminergic nigro-striatum system exerts a protective action on the impulse transfer on monosynaptic connections from the cortex to striatum.

[Efferent connections of the caudate nucleus of the cat studied using retrograde axonal transport of horseradish peroxidase]. / Efferentnye sviazi khvostatogo iadra koshi, issledovannye s pomoshch'iu retrogradnogo aksonnogo transporta peroksidazy khrena.

The origin of descending efferent pathways from the caudate nucleus was studied by retrograde axonal transport of horseradish peroxidase. Widespread topically organized projections were observed to the paleostriatum and the substantia nigra and less numerous to the thalamus. The main source of these projections were small and medium-size cells. A particular role of the subthalamic nucleus in the descending efferent system of the caudate nucleus is pointed out: this nucleus besides projections to the caudate nucleus itself possesses direct connections with principal output structures of the latter--the the paleostriatum and substantia nigra.

Rhythmic activity of the brain evoked by local injections of carbachol into subcortical nuclei.

The effect of local injections of carbachol into the caudate nucleus and individual nuclei of the thalamus on the electrocorticogram of the anterior portion of the brain was investigated in unanesthetized, immobilized cats. It was shown that chemical stimulation of subcortical structures, like electrical stimulation, can induce spindle-like activity and a recruitment response. The appearance of these reactions after injections of carbachol both into the caudate nucleus and into individual nuclei of the thalamus indicates the existence of a functionally unified caudate-thalamic cholinoreceptive system, responsible for the slow wave rhythmic activity.

[Divergence of axon collaterals of substantia nigra neurons in the forebrain of the rat: double labeling with fluorochromes and horseradish peroxidase]. / Divergentsiia aksonnykh kollateralei neironov chernoi substantsii v perednem mozge krysy: dvoinoe mechenie fliuorokhromami i peroksidazoi khrena.

The origin of divergent and non-divergent pathways from substantia nigra to the thalamus were studied in experiments on rats using retrograde axonal transport of luminescent tracers and horse-radish peroxidase. Two efferent projection systems are shown: the first--with divergence of axon collaterals to the caudato-putamen of both hemispheres, caudato-putamen and globus pallidus, caudato-putamen and nucleus accumbens, ipsilaterally; the second system is directed to the thalamus, and does not form axon collaterals to striatal structures.

[Afferent connections of the caudate nucleus of cats studied using the technic of retrograde axonal transport]. / Afferentnye sviazi khvostatogo iadra koshki, issledovannye s pomoshch'iu metoda retrogradnogo aksonnogo transporta.

The horseradish peroxidase method was used to investigate the sources of direct and indirect connections to the caudate nucleus in the cat. It is shown that different cortical and subcortical areas contain cells projecting to the caudate nucleus. Labelled neurons after caudate injections were also found in the globus pallidus. Along with the intralaminar complex the ventral anterior and mediodorsal nuclei were found to be the most significant sources of thalamo-caudate projections. The most caudal projection to the caudate nucleus in the cat was demonstrated by finding labelled neurons in the locus coeruleus. The functional significance of the investigated afferent connections of the caudate nucleus is discussed.

[Horseradish peroxidase-labeled cells as sources of the spinoreticular and spinothalamic systems of the brain]. / Mechennye peroksidazoi khrena istochniki spinoretikuliarnykh i spinotalamicheskikh sistem mozga.

The cells of spinoreticular and spinothalamic fibrous systems of the cat brain were studied by the method of axone transmission of horse-radish peroxidase (HP). A dense accumulation of HP-labeled neurons establishing direct relations with the reticular formation and thalamus was seen in the upper segments of the spinal cord. In the lower segments these zones were confined to the medial part of the ventral horn and the intermediate zone of the gray matter. The neurons established direct connections with contralateral nuclei of the reticular formation as well as with the thalamus ipsi- and contralateral nuclei. Possible pathways of transmitting somatic and pain sensitivity are discussed.