Cat Caudate Research Articles

Structural Basis of the Inhibitory Functions of the Efferent Systems of the Parietal Cortex

The relative quantitative distributions of all associative and descending efferent fibers and the ultrastructural organization of terminals of the parietal cortex (fields 5 and 7) in the caudate nucleus (NC) and red nucleus (NR) in cats were studied after local point lesions to the cortex in these fields. The maximal projections of associative fibers were found to be to the fundal fields of the motor cortex and the Clare–Bishop field, with a moderate projection to fields 31 and 19, and occasional degenerating fibers to fields 1, 2, 3a, 3d, 30, and 23. Among descending fibers, the most extensive projections were to the NC, NR, reticular nucleus, and midbrain nuclei, as well as to the pontine nuclei, where immunocytochemical studies revealed mainly GABAergic terminals. Electron microscopic studies led to the suggestion that the influences of the parietal cortex are mediated by axospinous synapses of intermediate short-axon spiny cells of the dorsolateral part of the head of the NC and axodendritic synapses of Golgi II cells in the parvocellular part of the NR. Given the maximal involvement of the fundal fields of the motor cortex and the inhibitory subcortical (NC) and stem nuclei (NR, reticular nuclei of the thalamus), midbrain, and pontine nuclei), we suggest that they serve as the morphological substrate mediating the inhibitory integrative function of the parietal cortex.

Spatio-temporal visual properties in the ascending tectofugal system

AbstractOur study compares the spatio-temporal visual receptive field properties of different subcortical stages of the ascending tectofugal visual system. Extracellular single-cell recordings were performed in the superficial (SCs) and intermediate (SCi) layers of the superior colliculus (SC), the suprageniculate nucleus (Sg) of the posterior thalamus and the caudate nucleus (CN) of halothane-anesthetized cats. Neuronal responses to drifting gratings of various spatial and temporal frequencies were recorded. The neurons of each structure responded optimally to low spatial and high temporal frequencies and displayed narrow spatial and temporal frequency tuning. The detailed statistical analysis revealed that according to its stimulus preferences the SCs has markedly different spatio-temporal properties from the homogeneous group formed by the SCi, Sg and CN. The SCs neurons preferred higher spatial and lower temporal frequencies and had broader spatial tuning than the other structures. In contrast to the SCs the visually active SCi, as well as the Sg and the CN neurons possessed consequently similar spatio-temporal preferences. These data support our hypothesis that the visually active SCi, Sg and CN neurons form a homogeneous neuronal population given a similar spatio-temporal frequency preference and a common function in processing of dynamic visual information.

Striatal Alterations of Secretogranin-1, Somatostatin, Prodynorphin, and Cholecystokinin Peptides in an Experimental Mouse Model of Parkinson Disease

The principal causative pathology of Parkinson disease is the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta projecting to the striatum in the brain. The information regarding the expression of neuropeptides in parkinsonism is very limited. Here we have elucidated striatal neuropeptide mechanisms in experimental parkinsonism using the unilateral 6-hydroxydopamine model to degenerate dopamine neurons. A thoroughly controlled sample preparation technique together with a peptidomics approach and targeted neuropeptide sequence collections enabled sensitive detection, identification, and relative quantitation of a great number of endogenous neuropeptides. Previously not recognized alterations in neuropeptide levels were identified in the unilateral lesioned mice with or without subchronic 3,4-dihydroxy-L-phenylalanine administration, the conventional treatment of Parkinson disease. Several of these peptides originated from the same precursor such as secretogranin-1, somatostatin, prodynorphin, and cholecystokinin. Disease-related biotransformation of precursors into individual peptides was observed in the experimental model of Parkinson disease. Several previously unreported potentially biologically active peptides were also identified from the striatal samples. This study provides further evidence that neuropeptides take part in mediating the central nervous system failure associated with Parkinson disease.

MPTP-induced suppression of corticofugal influences on neurons of the cat caudate nucleus

In acute experiments on cats, we demonstrated that the relative number of neurons of the caudate nucleus responding to stimulation of the motor cortex with latencies shorter than 8.0 msec significantly decreased, as compared with the control, after destruction of the nigro-striatal dopaminergic system caused by a series of injections of the neurotoxin MPTP. Within 1.5 months, the number of these cells gradually recovered. We conclude that in the norm dopamine exerts an inhibitory effect on glutamatergic cortico-striatal impulsation. We hypothesize that the blockade of transmission through cortico-striatal synaptic connections under conditions of dopamine deficiency is realized due to the toxic effect of glutamate released in excessive amounts on the corresponding receptors in the above synapses.

Soma size of substantia nigra neurons increases after a prenatal neocortical lesion in cats

Seeking an explanation for an increase in volume of the caudate nucleus in adult cats that had sustained a fetal unilateral neocortical lesion, we investigated possible morphological changes in the reciprocally interconnected substantia nigra. In fetal-lesioned cats the cross-sectional area of neuronal somata in substantia nigra, pars reticulata was 33% larger than in control cats ( P<0.05), while in pars compacta there was a marked tendency to an increase (25%, P<0.06). This size increase might have caused the survival of a larger number of caudate nucleus neurons during development, and thus contributed to the reported increase in caudate nucleus volume.

Double retrograde tracer study of the corticostriatal projections to the cat caudate nucleus.

The distribution of corticostriatal neurons projecting to the caudate nucleus was examined in the cat by retrograde fluorescent tracers. Thus, Fast Blue and Diamidino Yellow were concomitantly injected in different rostrocaudal, dorsoventral, or mediolateral sectors of the caudate nucleus. The main findings of this study are: 1) few double-labeled cells were found after two injections in different sectors of the caudate nucleus; 2) double-labeled neurons were more abundant after adjacent injections and they were mainly located in 6 alpha beta, dorsolateral prefrontal, dorsomedial prefrontal, prelimbic, anterior limbic, sylvian anterior, and rostral part of cingulate cortical areas; and 3) there were variations in the spatial organization of the corticostriatal neurons in different cortical areas projecting to various parts of the caudate nucleus.

Double retrograde tracer study of the corticostriatal projections to the cat caudate nucleus

The distribution of corticostriatal neurons projecting to the caudate nucleus was examined in the cat by retrograde fluorescent tracers. Thus, Fast Blue and Diamidino Yellow were concomitantly injected in different rostrocaudal, dorsoventral, or mediolateral sectors of the caudate nucleus. The main findings of this study are: 1) few double-labeled cells were found after two injections in different sectors of the caudate nucleus; 2) double-labeled neurons were more abundant after adjacent injections and they were mainly located in 6 alpha beta, dorsolateral prefrontal, dorsomedial prefrontal, prelimbic, anterior limbic, sylvian anterior, and rostral part of cingulate cortical areas; and 3) there were variations in the spatial organization of the corticostriatal neurons in different cortical areas projecting to various parts of the caudate nucleus.

Anatomical re-evaluation of the corticostriatal projections to the caudate nucleus: a retrograde labeling study in the cat.

The distribution of cortical neurons projecting to the cat caudate nucleus (CN) was examined using retrograde labeling methods. Single injections of either horseradish peroxidase conjugated with wheat germ agglutinin (HRP-WGA), or the fluorescent tracers Fast Blue (FB) or Diamidino Yellow (DY) were made into different regions of the CN. This study confirms the following previous findings. (1) Labeled neurons were observed in the frontal and parieto-temporal cortices. (2) The corticocaudate cells were mainly located in layer V, although some cells were also observed in layer III and occasionally in layers II and VI. (3) Dorsal injections into the rostral CN yielded more dorsal labeling in the cerebral cortex. However, ventral cortical areas such as the ventral part of the prelimbic (PL) cortical area and the insular cortex (sylvian anterior (SA), agranular and disgranular insular areas) presented retrograde labeling after both dorsal and ventral injections into the CN. (4) Dorsal injections into the CN labeled all subdivisions of areas 4 and 6 whereas the ventral ones labeled only the areas 4delta, 6alphabeta, 6aalpha, 6iffu. The novel findings of this study are as follows. (1) The cortical area 6betabeta and the dorsolateral prefrontal area (PfDl) were labeled in all our cases. In addition, PL, anterior limbic, SA and rostral part of cingulate (Cg) cortical areas were also labeled in most of our cases. (2) Ventral injections into the CN elicited a higher number of retrogradely labeled neurons in the ventral prefrontal area than dorsal injections. (3) A topographical relationship was found between the caudal CN and the dorsomedial prefrontal area so that dorsal injections in the caudal CN elicited retrograde labeling in the rostral PfDl, whereas ventral injections labeled the caudal PfDl. (4) A topography from dorsal to rostral and ventral to caudal was also observed between injections into the CN and PL and Cg. (5) A mediolateral topography was observed in the presylvian, cruciate and splenial sulci.

Double retrograde tracer study of the thalamostriatal projections to the cat caudate nucleus

The distribution of thalamostriatal neurons projecting to the cat caudate nucleus was examined by retrograde fluorescent tracers. Thus, Fast Blue and Diamidino Yellow were concomitantly injected in different rostrocaudal, dorsoventral, or mediolateral sectors of the caudate nucleus. The main findings of this study are as follows: (1) few double-labeled cells were found after two injections in different sectors of the caudate nucleus; (2) double-labeled neurons were more abundant after adjacent injections and they were mainly located in the caudal intralaminar nuclei, in the rhomboid nucleus and in the dorsal mediodorsal nucleus; and (3) there were variations in the spatial organization of the thalamostriatal neurons projecting to various sectors of the caudate nucleus in the different thalamic nuclei known to project to this part of the striatum. Synapse 32:80–92, 1999. © 1999 Wiley-Liss, Inc.

Double retrograde tracer study of the thalamostriatal projections to the cat caudate nucleus.

The distribution of thalamostriatal neurons projecting to the cat caudate nucleus was examined by retrograde fluorescent tracers. Thus, Fast Blue and Diamidino Yellow were concomitantly injected in different rostrocaudal, dorsoventral, or mediolateral sectors of the caudate nucleus. The main findings of this study are as follows: (1) few double-labeled cells were found after two injections in different sectors of the caudate nucleus; (2) double-labeled neurons were more abundant after adjacent injections and they were mainly located in the caudal intralaminar nuclei, in the rhomboid nucleus and in the dorsal mediodorsal nucleus; and (3) there were variations in the spatial organization of the thalamostriatal neurons projecting to various sectors of the caudate nucleus in the different thalamic nuclei known to project to this part of the striatum.

Differences in D 2 dopamine receptor binding in the neostriatum between cats hemidecorticated neonatally or in adulthood

In order to study differences in response to neocortical injury sustained at different ages at the neurotransmitter level, we examined the density in D 2 dopamine receptors in the neostriatum of cats hemidecorticated neonatally ( N=4) or in adulthood ( N=4), as well as in intact brains ( N=6). Receptor densities were measured using quantitative autoradiography and [ 3H]-spiperone binding in 12 regions of the neostriatum and nucleus accumbens septi. We found that the anterior lateral caudate nucleus on both sides of the brain contained a higher D 2 receptor density in neonatal-lesioned as compared to adult-lesioned brains. Ipsilateral to the lesion, the increase was 101% ( P<0.05) and contralaterally it amounted to 77% ( P<0.05). Moreover, this region of the ipsilateral caudate nucleus of neonatal-lesioned cats tended to be more densely labeled than that of intact brain by 58% ( P<0.1). D 2 receptor densities in adult-lesioned cats did not differ from that of intact controls. Comparison of these data with those of a former morphological study using the same animals suggested that this bilateral elevation of D 2 receptor density in neonatally lesioned brains represents a higher mean density of binding sites per neuron. The elevation in the neonatal-lesioned cats might be a response of the striatum to neuroplastic changes in the striatal neuropil, including the corticostriatal afferents, since such changes are different in neonatal- as compared to adult-lesioned cats.

Activity change of cat caudate neurons related to the learning of memory-guided saccade task

Activity change of cat caudate neurons related to the learning of memory-guided saccade task

2220 Activity change of cat caudate neurons related to the learning of memory-guided saccade task

2220 Activity change of cat caudate neurons related to the learning of memory-guided saccade task

1655 The activity of cat caudate neurons associated with memory-guided eye movement task

1655 The activity of cat caudate neurons associated with memory-guided eye movement task

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.

Heterogeneous topographical distribution of the striatonigral and striatopallidal neurons in the matrix compartment of the cat caudate nucleus.

The topographical organization of the striatonigral projection was investigated in the cat by comparing the localization and the intensity of labelling of retrogradely labelled cells in the caudate nucleus following one or multiple injections of horseradish peroxidase-wheat germ agglutinin into the center or along the rostrocaudal axis of the substantia nigra pars reticulata. Second, the localizations of retrogradely labelled striatopallidal neurons and of clusters of aggregated striatonigral neurons (as outlined by the transport of 14C-material) were compared in cats that received four horseradish peroxidase-wheat germ agglutinin injections into the internal segment of the globus pallidus and three nigral injections of 14C-amino acids into the substantia nigra pars reticulata. Two types of striatonigral neurons located predominantly within the matrix compartment were identified: poorly collateralized aggregated cells distributed in clusters and more numerous collateralized cells distributed outside the clusters. In addition, two cell types were distinguished within each cluster of aggregated neurons. Those innervating the center of the substantia nigra pars reticulata were observed after a single nigral injection of the tracer, whereas those projecting to distinct sites of the substantia nigra pars reticulata along a rostrocaudal axis were observed only after multiple injections. Striatal neurons innervating the internal segment of the globus pallidus were heterogeneously distributed predominantly within the matrix but outside the clusters of aggregated striatonigral neurons. Together, these results provide further evidence for the heterogeneity of the matrix and for the complexity of matrix striatonigral connections that send both diverging and converging signals to the substantia nigra pars reticulata.

Disturbances in cognitive activity and its neuropharmacological correction in structural-functional insufficiency of the head of the caudate nucleus in cats.

The participation of the head of the caudate nucleus in the organization of praxis, perception, gnosis, and "ideational operations" has been demonstrated. The broad spectrum of dysfunctions observed in the presence of caudate insufficiency was eliminated by a specific set of psychotropic preparations acting on classical neuromediator systems of the brain of cats.

Alterations in dopamine uptake sites and D1 and D2 receptors in cats symptomatic for and recovered from experimental parkinsonism

The administration of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to adult cats severely disrupts the dopaminergic innervation of the striatum. Animals display a parkinson-like syndrome, consisting of akinesia, bradykinesia, postural instability, and rigidity, which spontaneously recovers by 4-6 weeks after the last administration of MPTP. In this study we used quantitative receptor autoradiography to examine changes in DA uptake sites and DA receptors in the basal ganglia of normal, and symptomatic and recovered MPTP-treated cats. Consistent with the destruction of the nigrostriatal DA pathway, there was a severe loss of DA uptake sites, labeled with [3H]-mazindol, in the caudate nucleus (64-82%), nucleus accumbens (44%), putamen (63%), and substantia nigra pars compacta (SNc, 53%) of symptomatic cats. Following behavioral recovery, there were no significant changes in DA uptake site density. Significant increases of [3H]-SCH 23390 binding to D1 DA receptors were observed in the dorsal caudate (> 24%; P < 0.05) of symptomatic cats and in all regions of the caudate-putamen (> 30%; P < 0.05) of recovered animals. [3H]-SCH 23390 binding in the substantia nigra pars reticulata was half of that in the striatum and showed no changes in symptomatic or recovered animals. No alterations in the binding of [125I]-epidepride to D2 receptors was observed in any region of the striatum in either symptomatic or recovered animals. [125I]-Epidepride binding in the SNc was decreased by > 36% (P < 0.05) following MPTP treatment. These data show that cats made parkinsonian by MPTP exposure have a significant decrease in the number of DA reuptake sites throughout the striatum and that recovery of sensorimotor function in these animals is not correlated with an increase in the number of striatal reuptake sites. Behavioral recovery, however, does seem to be correlated with a general elevation of D1 receptors throughout the striatal complex. The present data also show that direct correlations between changes in DA receptor regulation after a large DA depleting lesion and behavioral deficits or recovery from those deficits are difficult and that the relationships between DA receptors/transporters and behavior require further study.

The distribution of cholinergic perikarya with respect to enkephalin-rich patches in the caudate nucleus of the adult cat

The distribution of cholinergic interneurons with respect to enkephalin-rich patches in the caudate nucleus of the cat was examined using both computer-assisted 3-D reconstruction and immunocytochemical techniques. Examination of the 3-D distribution of perikarya staining for choline acetyltransferase (ChAT) revealed that these cells were not evenly distributed within the caudate nucleus but exhibited areas of increased and decreased density. Comparison of the 3-D distribution of cholinergic perikarya to that of the enkephalin-rich patches indicated that areas of increased ChAT+ cell density often corresponded to the positions of enkephalin-rich patches within the dorsal-lateral caudate nucleus. At more ventral regions, there was no clear correspondence between areas of increased ChAT+ cell density and enkephalin-rich patches. In agreement with these observations, a quantitative analysis of sections double-labeled for ChAT and enkephalin revealed that the density of cholinergic neurons within enkephalin-rich patches was twice that in the surrounding tissue in the dorsal region of the caudate nucleus. In contrast at more ventral levels, the difference in the density of ChAT+ cells in enkephalin-rich patches did not significantly differ from that in the surrounding striatal tissue. Both the results of the 3-D and the double-labeling analysis suggest that cholinergic neurons are not evenly distributed within the caudate nucleus of the cat but form loose clusters which are associated dorsally with the enkephalin-rich patches. These results also provide further evidence of heterogeneity within the striosomal compartment in the cat.

Nitric oxide synthase inhibition reduces caudate injury following transient focal ischemia in cats.

We tested the hypothesis that inhibiting nitric oxide production either before or during transient focal ischemia affects early postischemic brain injury. Halothane-anesthetized cats underwent 1 hour of left middle cerebral artery occlusion plus 3 hours of reperfusion. Pretreatment groups received either intravenous N omega-nitro-L-arginine methyl ester (L-NAME; 10 mg/kg, n = 10) or an equal volume of diluent (10 mL saline, n = 10) over 30 minutes before ischemia. Posttreatment groups received intravenous L-NAME (10 mg/kg) over 30 minutes from 45 minutes of ischemia to 15 minutes of reperfusion (n = 10) or intravenous L-NAME (10 mg/kg) plus L-arginine (200 mg/kg) over the same period followed by continuous L-arginine infusion (200 mg/kg per hour) for the remainder of reperfusion (n = 10). Microsphere-determined blood flow to ipsilateral caudate nucleus and inferior temporal cortex decreased to the same extent during ischemia and recovered to the same extent during reperfusion in the four groups. Triphenyltetrazolium-determined injury volume of ipsilateral caudate nucleus in cats treated with L-NAME before or during ischemia (42 +/- 7% and 42 +/- 3% of caudate nucleus, respectively; mean +/- SE) was less (P < .05) compared with that in cats pretreated with saline (72 +/- 5%) or cats treated with L-NAME plus L-arginine (68 +/- 5%). Ipsilateral cerebral hemispheric injury volume was similar among the four groups (23 +/- 5%, 13 +/- 3%, 18 +/- 5%, and 29 +/- 5% of hemisphere in groups treated with L-NAME before ischemia and during ischemia, the saline-treated group, and the group treated with L-NAME plus L-arginine, respectively). Inhibition of nitric oxide synthase decreases caudate injury volume from transient focal cerebral ischemia in cats. The beneficial effect is reversed by L-arginine and is not caused by favorable redistribution of blood flow during ischemia and reperfusion. Because L-NAME was efficacious when administered at reperfusion, nitric oxide generated during reperfusion appears to contribute to caudate injury.