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C R Dermon

Publications and source records attributed to C R Dermon.

At least 19 recordsLinked to original sources

Passive avoidance training is correlated with decreased cell proliferation in the chick hippocampus.

One-trial passive avoidance learning (PAL), where the aversive stimulus is the bitter-tasting substance methylanthranilate (MeA), affects neuronal and synaptic plasticity in learning-related areas of day-old domestic chicks (Gallus domesticus). Here, cell proliferation was examined in the chick forebrain by using 5-bromo-2-deoxyuridine (BrdU) at 24 h and 9 days after PAL. At 24 h post-BrdU injection, there was a significant reduction in labelling in MeA-trained chicks in both the dorsal hippocampus and area parahippocampalis, in comparison to controls. Moreover, double-immunofluorescence labelling for BrdU and the nuclear neuronal marker (NeuN) showed a reduction of neuronal cells in the dorsal hippocampus of the MeA-trained group compared with controls (35 and 49%, respectively). There was no difference in BrdU labelling in hippocampal regions between trained and control groups of chicks at 9 days post-BrdU injection; however, the number of BrdU-labelled cells was considerably lower than at 24 h post-BrdU injection, possibly due to migration of cells within the telencephalon rather than cell loss as apoptotic analyses at 24 h and 9 days post-BrdU injection did not demonstrate differences in cell death between treatment groups. Cortisol levels increased in the chick hippocampus of MeA-trained birds 20 min after PAL, suggesting the possibility of a stress-related mechanism of cell proliferation reduction in the hippocampus. In contrast to hippocampal areas, the olfactory bulb, an area strongly stimulated by the strong-smelling MeA, showed increased cell genesis in comparison to controls at both 24 h and 9 days post-training.

Animals↗

Unilateral optic nerve crush induces bilateral retinal glial cell proliferation.

The post-injury responses of retinal ganglion cells elicit a number of glial reactions which have not been completely understood. The bilateral pattern of non-neuronal retinal cell proliferation was examined in association with the differential fates of unilaterally injured adult retinal ganglion cells by means of bromodeoxyuridine (BrdU) immunocytochemistry. Lateralization of the glioproliferative events was studied by analysing both the experimental and the uninjured contralateral as well as matched retinas of sham-operated animals. Control adult rat retina included very few BrdU-positive cells within the nerve fibre and ganglion cell layers; however, experimental retinas of degenerating groups exhibited statistically significantly higher densities of newborn cells in most layers. Clusters of labelled cells were found in the inner plexiform layer related to OX-42 staining, indicating their microglial nature. Indeed, double-labelling experiments, after short-term unilateral optic nerve crushing, identified proliferating retinal glial cells in vivo. Both types of glia, astroglial and microglial cells, exhibited BrdU-positive labelling in injured as well as uninjured experimental rat retinas. Moreover, microglial proliferating cells were also identified in explanted retinal pieces after 2 days in culture. Affected and contralateral retinas responded similarly to the unilateral experimental manipulations applied with respect to BrdU labelling. The acute glial responses observed suggest that bilateral glial proliferation might represent a common response related to degeneration events in both retinas, i.e. ipsi- and contralateral to the experimental injury.

Animals↗

Differential effects of testosterone on protein synthesis activity in male and female quail brain.

In Japanese quail, testosterone (T) increases the Nissl staining density in the medial preoptic nucleus (POM) in relation to the differential activation by T of copulatory behavior. The effect of T on protein synthesis was quantified here in 97 discrete brain regions by the in vivo autoradiographic (14)C-leucine (Leu) incorporation method in adult gonadectomized male and female quail that had been treated for 4 weeks with T or left without hormone. T activated male sexual behaviors in males but not females. Overall Leu incorporation was increased by T in five brain regions, many of which contain sex steroid receptors such as the POM, archistriatum and lateral hypothalamus. T decreased Leu incorporation in the medial septum. Leu incorporation was higher in males than females in two nuclei but higher in females in three nuclei including the hypothalamic ventromedial nucleus. Significant interactions between effects of T and sex were seen in 13 nuclei: in most nuclei (n=12), T increased Leu incorporation in males but decreased it in females. The POM boundaries were defined by a denser Leu incorporation than the surrounding area and incorporation was increased by T more in males (25%) than in females (6%). These results confirm that protein synthesis in brain areas relevant to the control of sexual behavior can be affected by the sex of the subjects or their endocrine condition and that T can have differential effects in the two sexes. These anabolic changes should reflect the sexually differentiated neurochemical mechanisms mediating behavioral activation.

Animals↗

Passive avoidance training enhances cell proliferation in 1-day-old chicks.

One-day-old domestic chicks were injected i.p. with bromodeoxyuridine (BrdU) before training on a one-trial passive avoidance task where the aversive experience was a bead coated with a bitter tasting substance, methyl anthranilate (MeA). Animals were tested 24 h later; those avoiding (if MeA-trained) or pecking if water (W)-trained (which they peck appetitively), along with a group of untrained naïve chicks, were used to determine cell proliferation either 24 h or 9 days post BrdU injection. In all three groups, BrdU positive cells were identified sparsely throughout the forebrain but labelling was pronounced around ventricular zone (VZ) surfaces at both 24 h and 9 days post-BrdU-injection. Double immunolabelling with neuronal specific antibodies, to either NeuN, or beta-tubulin III, confirmed that most BrdU labelled cells appeared to be neurons. Unbiased stereological analysis of labelled cells in selected forebrain areas 24 h post BrdU injection showed a significant MeA-training induced increase in labelled cells in both the dorsal VZ surface bordering the intermediate and medial hyperstriatum ventrale (IMHV) and the tuberculum olfactorium (TO). By 9 days post-BrdU-injection, there was a significantly greater number of BrdU labelled cells in MeA-trained birds within the IMHV, lobus parolfactorius (LPO) and TO. These results demonstrate that avoidance training in 1-day-old chicks has a marked effect on cell proliferation, in the LPO and IMHV, regions of the chick previously identified as a key loci of memory formation, and in a second region (TO), which has olfactory functions, but has not been previously investigated in relation to avoidance learning.

Animals↗

Cell genesis in the hypothalamus is associated to the sexual phase of a hermaphrodite teleost.

The present study aimed to define sex differences in the genesis of hypothalamic and telencephalic cells in the adult brain of male, female and under sex reversal teleosts (Sparus aurata). Application of 5-bromo-2-deoxyuridine immunocytochemistry and quantification of the newborn cells using the disector method, determined a statistically significant difference in the dorsal hypothalamic ventricular area between sexual phases. Female brain exhibited a higher number of newborn cells, suggesting that estrogens possibly influence higher mitotic activity. In contrast, paraventricular organ and ventral nucleus of the ventral telencephalon did not show any significant changes, while cell proliferation differences in the preoptic area were correlated with age. The sex-specific cell proliferation pattern in the hypothalamus adds important information on the cellular mechanisms that underlie sex change in a protandrous hermaphrodite teleost.

Analysis of Variance↗

Effects of lesions of the medial preoptic nucleus on the testosterone-induced metabolic changes in specific brain areas in male quail.

The effects of bilateral lesions of the medial preoptic nucleus in association with testosterone on the metabolic activity in discrete brain regions was studied quantitatively by the in vivo autoradiographic 2-deoxyglucose method. Adult male quail were castrated and then left without hormone replacement therapy or treated with testosterone or treated with testosterone and submitted to a bilateral lesion of the medial preoptic nucleus, a brain region that plays a key role in the activation of male copulatory behavior by testosterone. Treatment for about 10 days with testosterone activated the expression of the full range of male sexual behaviors and these behaviors were completely suppressed by the medial preoptic nucleus lesions. Mapping of 2-deoxyglucose uptake revealed both increases and decreases of metabolic activity in discrete brain regions associated with the systemic treatment with testosterone as well as with the lesion of the medial preoptic nucleus. Testosterone affected the oxidative metabolism in brain areas that are known to contain sex steroid receptors (such as the nucleus taeniae and the paraventricular and ventromedial nuclei of the hypothalamus) but also in nuclei that are believed to be devoid of such receptors. Effects of testosterone in these nuclei may be indirect or reflect changes in terminals of axons originating in steroid-sensitive areas. Bilateral medial preoptic nucleus lesions affected 2-deoxyglucose uptake in a variety of brain regions. Some of these regions are known to be mono-synaptically connected to the medial preoptic nucleus. Metabolic depression in these areas may reflect retrograde changes in the neurons projecting to the damaged field.The metabolic changes identified in the present study confirm the prominent role of the preoptic area in the control of sexual behavior, show that changes in the physiology of the visual system represent one of the ways through which testosterone influences the occurrence of this behavior and demonstrate that the medial preoptic nucleus has marked effects on the metabolic activity in a variety of limbic and telencephalic structures. This study also indicates that the medial preoptic nucleus affects the activity of the area ventralis of Tsai, a dopaminergic area known to send projections to a variety of hypothalamic, thalamic and mesencephalic nuclei that are implicated in the control of male sexual behavior. These data therefore support the notion that the control of the dopaminergic activity in the area ventralis of Tsai by the medial preoptic nucleus represents one of the ways through which the medial preoptic area regulates male reproductive behavior.

Animals↗

Proliferation zones in the adult brain of a sequential hermaphrodite teleost species (Sparus aurata).

Teleost sex change is an important model to understand general principles of sexual differentiation and plasticity in the adult brain. The present study is the first to examine the proliferation zones in the adult brain of males, females and sex-changing individuals of a protandrous teleost species (Sparus aurata), by means of 5-bromo-2-deoxyuridine immunocytochemistry. Postnatal neurogenesis in the marine teleost brain was found in ventricular and subventricular areas of the brain that in most cases coincided with the embryonic proliferation zones. The molecular layer of corpus and valvula cerebelli exhibited the highest mitotic activity in the adult brain. High mitotic activity was observed in the hypothalamic, thalamic and telencephalic ventricular areas, as well as the dorsal and ventral rim of the optic tectum. Most of the labeled cells were elongated, indicating the initiation of migratory activity. There were no qualitative differences in the distribution of proliferation zones between the sex phases studied with the exception of the ventricular region of the dorsal hypothalamic area. Volume fraction analysis of the area occupied by the labeled cells suggested that this region included higher densities of newborn cells in the female animals. The proliferation pattern in the adult gilthead sea bream brain is in agreement with the hypothesis of the continuous generation of new cells in the teleost brain. Moreover, our data propose that cell proliferation differences possibly existing in the ventricular region of the dorsal hypothalamus between sexual phases, might be involved in central mechanisms of sexual plasticity in protandrous hermaphrodite teleosts.

Animals↗

Performance of appetitive or consummatory components of male sexual behavior is mediated by different brain areas: a 2-deoxyglucose autoradiographic study.

The in vivo autoradiographic deoxyglucose method was used to identify the functional brain circuits that are involved in the performance of appetitive and consummatory components of male sexual behavior in Japanese quail (Coturnix japonica). Two groups of castrated, testosterone-treated male quail were trained during 12 sessions to associate the view of a female behind a window with the opportunity to interact freely and to copulate with her. They developed, as a consequence, a social proximity response (staying close and looking through the window providing a view of the female) that has been used in previous experiments to measure appetitive sexual behavior. A third control group (also castrated and treated with testosterone) was allowed to view the female but not to copulate with her and therefore did not develop this proximity response. 2-14C-deoxyglucose was then injected i.p. to these birds and they were allowed to either copulate freely with a female (consummatory sexual behavior group) or express the social proximity response (appetitive sexual behavior group). The control group was provided a view of the female but these birds, although they were exposed to the same stimuli as birds in the appetitive group, did not express the social proximity response because they had never learned the association with the opportunity to copulate. Birds were killed 45 min after the deoxyglucose injection and their brains were processed for autoradiography. Densitometric analyses of the autoradiograms revealed that the expression of appetitive or consummatory aspects of male sexual behavior was associated with significant increases by comparison with the control group in the deoxyglucose incorporation in the nucleus mesencephalicus lateralis, pars dorsalis and in the nucleus leminsci lateralis. In addition, an increase in the deoxyglucose incorporation was specifically observed in the paleostriatum primitivum, rostral preoptic area, nucleus intercollicularis, nucleus interpeduncularis and third nerve but a decrease was observed in the dorsomedial part of the hippocampus and in the nucleus nervi oculomotori in birds of the consummatory sexual behavior group by comparison with controls. By contrast, in the appetitive sexual behavior group, significant increases in deoxyglucose incorporation were observed in two telencephalic areas, the intermediate hyperstriatum ventrale and neostriatum caudolaterale by comparison with the controls, but decreases were detected in the stratum griseum et fibrosum superficiale of optic tectum by comparison with the consummatory behavior group. These studies demonstrate that the performance of appetitive or consummatory components of male sexual behavior affects in a specific manner the deoxyglucose uptake and accumulation in specific regions of the quail brain. Changes in metabolic activity were observed in steroid-sensitive areas, in auditory, visual and vocal brain regions, and in brain nuclei related to motor behavior but also in association telencephalic and limbic structures. These changes in oxidative metabolism overlap to some extent with metabolic changes as revealed by immunocytochemistry for the immediate early gene products Fos and Zenk, but many specific reactions are also detected indicating that these techniques are not necessarily redundant and, together, they can provide a more complete picture of the brain circuits that are implicated in the control and performance of complex behaviors.

Animals↗

Passive avoidance learning involves alpha2-noradrenergic receptors in a day old chick.

Day-old chicks were trained on one-trial passive avoidance task, using methyl-anthranilate (MeA) as an aversive substance. Bilateral pharmacological manipulation of the intermediate hyperstriatum ventrale was performed by intracerebral application of an alpha2-noradrenergic agonist, clonidine (5 microM), or an antagonist, rauwolscine (300 microM). Only rauwolscine application (pre- or post-training) induced significant memory impairment. Quantitative receptor autoradiography was used to determine the kinetic properties of the binding sites for [3H]clonidine or [3H]rauwolscine in MeA-trained or water-trained (control) chicks, in forebrain areas known to be involved in avoidance learning. Scatchard analysis revealed that MeA-training resulted in a significant bilateral upregulation in the number of [3H]rauwolscine binding sites (Bmax) in the area of hyperstriatum ventrale. These findings suggest the importance of activation of alpha2-noradrenergic receptors in aversive learning in chicks.

Adrenergic alpha-Agonists↗

D-cycloserine causes transient enhancement of memory for a weak aversive stimulus in day-old chicks (Gallus domesticus).

The N-methyl-D-aspartate (NMDA) receptor plays an important role in acquisition of memory after one-trial passive avoidance training in day-old chicks. Here, we examined the effect of D-cycloserine, a partial agonist of the glycine site on the NMDA receptor, on memory retention after training on weak aversive stimuli (10% methyl anthranilate). Bilateral, or unilateral, intracranial injections of 5 microliters of 600 mumol.l-1 D-cycloserine (DCS) were made into the intermediate and medial hyperstriatum ventrale 5 min posttraining and chicks were tested either 30 min or 1, 6, or 24 h later. Enhanced memory retention (number of chicks avoiding) occurred after bilateral, or left hemisphere, injections of DCS (compared to saline-injected controls), when chicks were tested at 1 and 6 h, but not at 30 min or 24 h posttraining. These data suggest that activation of the glycine site on the NMDA receptor in the immediate posttraining period can transiently extend the retention period of memory for a weak aversive stimulus.

Animals↗

Functional anatomy of the thalamic centrolateral nucleus as revealed with the [14C]deoxyglucose method following electrical stimulation and electrolytic lesion.

The effects of electrical stimulation and electrolytic lesion of the thalamic intralaminar centrolateral nucleus were studied in the rat brain by means of the quantitative autoradiographic [14C]deoxyglucose method. Unilateral electrical stimulation of the centrolateral nucleus induced: (i) local increase in metabolic activity within the stimulated centrolateral nucleus and the ipsilateral thalamic mediodorsal nucleus, (ii) metabolic depression in all layers of the ipsilateral frontal cortex, (iii) bilateral increase in glucose consumption within the periaqueductal gray, pedunculopontine nucleus, and pontine reticular formation, and (iv) contralateral metabolic activation in the deep cerebellar nuclei. The unilateral electrolytic lesion of the thalamic centrolateral nucleus elicited metabolic depressions in several distal brain areas. The metabolic depression elicited in the mediodorsal, ventrolateral, and lateral thalamic nuclei, as well as in the caudate nucleus, the cingulate, and the superficial layers of forelimb cortex were ipsilateral to the lesioned side. The metabolic depression measured in the medulla and pons (medullary and pontine reticular formation, periaqueductal gray, locus coeruleus, dorsal tegmental, cuneiformis, raphe and pedunculopontine tegmental nuclei), the cerebellum (molecular and granular layers of the cerebellar cortex, interpositus and dentate nuclei), the mesencephalon (substantia nigra reticulata, ventral tegmental area and deep layers of the superior colliculus), the diencephalon (medial habenula, parafascicular, ventrobasal complex, centromedial and reticular thalamic nuclei), the rhinencephalon (dentate gyrus and septum), the basal ganglia (ventral pallidum, globus pallidus, entopeduncular and accumbens nuclei) and the cerebral cortex (superficial and deep layers of the frontal and parietal cortex, deep layers of the forelimb cortex) were bilateral. These functional effects are discussed in relation to known anatomical pathways. The bilateral effects induced by the centrolateral nucleus lesion reflect an important role of the centrolateral nucleus in the processing of reticular activating input and in the interhemispheric transfer of information. The cortical metabolic depression induced by centrolateral nucleus stimulation indicates the participation of this nucleus in attentional functions.

Animals↗

Laminar pattern of NADPH-diaphorase activity in the developing avian cerebellum.

The present study aimed to define the distribution of NADPH-diaphorase (NADPH-d) positive cells and fibers in the developing chick cerebellum. From embryonic day 9 (E9) until day E15 NADPH-d positive ascending axons, originating from pontine nuclei, targeted selectively the developing folia. Cerebellar cortex exhibited weak NADPH-d activity until day E15, when NADPH-d negative granule cells of external granular layer began inward migration. From that embryonic age, differentiated granule, Golgi II type cells and glomeruli of the internal granular layer exhibited gradually increasing diaphorase activity. In the molecular layer diffuse activity increased, possibly due to the development of the parallel fibers. Transient NADPH-d activity appeared on Purkinje somata (PC) at day E17 and by posthatching day 1 all PC were devoid of diaphorase activity. Our data support the hypothesis that neurons producing nitric oxide (NO) are involved in the activity dependent developmental processes for the establishment of connections and normal cytoarchitecture.

Amino Acid Oxidoreductases↗

Contralateral thalamic projections predominantly reach transitional cortices in the rhesus monkey.

Connections between the thalamus and the cortex are generally regarded as ipsilateral, even though contralateral connections exist as well in several adult mammalian species. It is not known, however, whether contralateral thalamocortical projections reach particular cortices or whether they emanate from specific nuclei. In the rhesus monkey different types of cortices, ranging from transitional to eulaminate, vary in their cortical connectional pattern and may also differ in their thalamic connections. Because olfactory and transitional prefrontal cortices receive widespread projections, we investigated whether they are the target of projections from the contralateral thalamus as well. With the aid of retrograde tracers, we studied the thalamic projections of primary olfactory (olfactory tubercle and prepiriform cortex) and transitional orbital (areas PAII, Pro, 13) and medial (areas 25, 24, 32) areas, and of eulaminate (areas 11, 12, 9) cortices for comparison. To determine the prevalence of neurons in the contralateral thalamus, we compared them with the ipsilateral in each case. The pattern of ipsilateral thalamic projections differed somewhat among orbital, medial, and olfactory cortices. The mediodorsal nucleus was the predominant source of projections to orbital areas, midline nuclei included consistently about 25% of the thalamic neurons directed to medial transitional cortices, and primary olfactory areas were distinguished by receiving thalamic projections predominantly from neurons in midline and intralaminar nuclei. Notwithstanding some broad differences in the ipsilateral thalamofrontal projections, which appeared to depend on cortical location, the pattern of contralateral projections was consistent with cortical type rather than location. Labeled neurons in the contralateral thalamus were noted in midline, the magnocellular sector of the mediodorsal nucleus, the anterior medial and intralaminar nuclei, and ranged from 0 to 14% of the ipsilateral; they were directed primarily to olfactory and transitional orbital and medial cortices but rarely projected to eulaminate areas. Several thalamic nuclei projected from both sides to olfactory and transitional areas, but issued only ipsilateral projections to eulaminate areas. Though ipsilateral thalamocortical projections predominate in adult mammalian species, crossed projections are a common feature in development. The results suggest differences in the persistence of contralateral thalamocortical interactions between transitional and eulaminate cortices.

Animals↗

Functional metabolic mapping of the rat brain during unilateral electrical stimulation of the subthalamic nucleus.

The alterations in local metabolic activity of several anatomically distinct brain areas were investigated by means of the quantitative autoradiographic 2-deoxy-D-[1-14C]glucose method in awake rats during unilateral electrical stimulation of the subthalamic nucleus (STH). Unilateral electrical stimulation of the STH induced local metabolic activation (by 70% as compared with the control group), as well as distal metabolic activations in the substantia nigra reticulata (by 34%), globus pallidus (by 19%), entopeduncular nucleus (by 18%), deep layers of the superior colliculi (by 15%), and parafascicular thalamic nucleus (by 18%), ipsilaterally to the stimulated side. The ventrolateral motor thalamic nucleus as well as the limbic components, posterior cingulate cortex, and anteroventral thalamic nucleus displayed bilateral metabolic activations (by 20-28%). These results indicate that, in addition to its known ipsilateral motor connections, each STH is functionally related to the limbic system bilaterally. It is suggested that the STH is a site where the central motor information is accessible to the limbic system. Quantitative image analysis of individual serial sections in the STH, substantia nigra, and globus pallidus revealed a consistent dorsoventral pattern of topographic interrelations. Stimulation of either the dorsal or the ventral subdivision of the STH induced always stronger activation in the dorsal compartment of the substantia nigra and in the ventral compartment of the globus pallidus. These results suggest that the earlier-described inversion of the dorsoventral functional correspondence between the substantia nigra and globus pallidus may be partly mediated via the subthalamic nerve cells projecting collateral axons to both these areas.

Animals↗

Bilateral cerebral metabolic effects of pharmacological manipulation of the substantia nigra in the rat: unilateral intranigral application of the inhibitory GABAA receptor agonist muscimol.

Rates of cerebral glucose utilization were measured by means of the autoradiographic 2-deoxy-D[1-14C]glucose technique in the rat brain in order to determine the metabolic effects of unilateral intranigral application of the GABAA agonist muscimol upon the substantia nigra and its targets. Intranigral injection of 1.5 microliters 0.3 M muscimol (52 micrograms total dose) induced local metabolic activation in the injected substantia nigra reticulata (by 87% as compared to the control group), and distal metabolic depressions in the nucleus accumbens, striatum, globus pallidus and subthalamic nucleus only ipsilaterally to the injected nigra. The remaining basal ganglia components, including the substantia nigra compacta and the entopeduncular nucleus were bilaterally unaffected. Among the principal efferent projections of the substantia nigra reticulata, the ventromedial and centrolateral thalamic nuclei as well as the deep layers of the superior colliculi were metabolically depressed bilaterally, whereas the ventrolateral, parafascicular and mediodorsal thalamic nuclei as well as the pedunculopontine nucleus displayed metabolic depressions ipsilateral to the muscimol-injection nigra. The ventromedial and centrolateral thalamic nuclei were depressed by 41 and 42%, respectively, in the ipsilateral side, and by 30 and 26% in the contralateral side, when compared to the respective values of the control group of rats. Furthermore, unilateral intranigral injection of 0.3 M muscimol induced metabolic depressions in reticular, intralaminar and prefrontal thalamocortical areas mostly ipsilateral to the injected nigra, as well as in limbic areas bilaterally. It is suggested that the present findings are due to a postsynaptic effect of muscimol on the nigral GABAergic cells and to a consequent metabolic depression of the basal ganglia and associated thalamocortical areas, in contrast to an earlier suggested presynaptic nigral effect of lower doses of intranigrally injected muscimol which induced metabolic activations within the same network. This suggestion is further supported by the fact that intranigrally injected substrate P19 induced similar effects to those elicited by the lower doses of intranigral muscimol and opposite to those induced at present by the higher muscimol dose. Moreover, it is further substantiated that the nigrothalamic GABAergic system is responsible for considerable transfer of information from one substantia nigra reticulata to the ipsilateral basal ganglia and associated thalamocortical components as well as to bilateral motor, intralaminar and limbic areas.

Animals↗

Bilateral cerebral metabolic effects of pharmacological manipulation of the substantia nigra in the rat: unilateral intranigral application of the putative excitatory neurotransmitter substance P.

The metabolic activity of several anatomically distinct brain areas was investigated by means of the quantitative autoradiographic 2-deoxy-D[1-14C]glucose method in awake rats following unilateral intranigral application of the putative excitatory neurotransmitter substance P. The primary goal was to determine the metabolic effects of substance P on the substantia nigra and its targets. Intranigral injection of 1 mM substance P (1.5 microliters) induced metabolic activation locally in the substantia nigra reticulata by 117% and substantia nigra compacta by 35%, as well as distally in the contralateral substantia nigra reticulata by 22% and contralateral substantia nigra compacta by 21%. All the basal ganglia components, the striatum, pallidum, entopeduncular, subthalamic nucleus and nucleus accumbens displayed bilateral metabolic activations after unilateral intranigral substance P injection. Among the principal reticulata efferent projections, the ventromedial, ventrolateral, parafascicular, mediodorsal and centrolateral thalamic nuclei, as well as the pedunculopontine nucleus displayed bilateral metabolic activations after intranigral substance P application. Moreover, unilateral intranigral substance P injection elicited metabolic activations in the thalamic and cortical components of the reticular, intralaminar, limbic and prefrontal systems, mostly bilateral. It is suggested that substance P applied into one substantia nigra reticulata activates the compacta nigrostriatal dopaminergic and the reticulata nigrothalamic GABAergic outputs inducing distal metabolic effects, similar to those elicited by unilateral nigral electrical stimulation [Savaki et al. (1983) J. comp. Neurol. 213, 46-65] and, opposite to several of those induced by intranigral injection of the inhibitory GABAA agonist muscimol [Savaki et al. (1992) Neuroscience 50, 781-794]. Furthermore, it is suggested that the ipsilateral basal ganglia effects induced by intranigral substance P application are mediated via both the compacta dopaminergic nigrostriatal projection and the reticulata GABAergic nigro-thalamocortico-striatal loop, whereas the contralateral basal ganglia and associated thalamocortical effects are due to the activation of the GABAergic reticulata efferents and are mediated via an interthalamic circuitry involving the motor, reticular and intralaminar thalamic nuclei.

Animals↗

Diverse thalamic projections to the prefrontal cortex in the rhesus monkey.

We studied the sources of thalamic projections to prefrontal areas of nine rhesus monkeys with the aid of retrograde tracers (horseradish peroxidase or fluorescent dyes). Our goal was to determine the proportion of labeled neurons contributing to this projection system by the mediodorsal (MD) nucleus compared to those distributed in other thalamic nuclei, and to investigate the relationship of thalamic projections to specific architectonic areas of the prefrontal cortex. We selected areas for study within both the basoventral (areas 11, 12, and ventral 46) and the mediodorsal (areas 32, 14, 46, and 8) prefrontal sectors. This choice was based on our previous studies, which indicate differences in cortical projections to these two distinct architectonic sectors (Barbas, '88; Barbas and Pandya, '89). In addition, for each sector we included areas with different architectonic profiles, which is also relevant to the connectional patterns of the prefrontal cortices. The results showed that MD included a clear majority (over 80%) of all thalamic neurons directed to some prefrontal cortices (areas 11, 46, and 8); it contributed just over half to some others (areas 12 and 32), and less than a third to area 14. Clusters of neurons directed to basoventral and mediodorsal prefrontal areas were largely segregated within MD: the former were found ventrally, the latter dorsally. However, the most striking findings establish a relationship between thalamic origin and laminar definition of the prefrontal target areas. Most thalamic neurons directed to lateral prefrontal cortices, which are characterized by a high degree of laminar definition (areas 46 and 8), originated in the parvicellular and multiform subdivisions of MD, and only a few were found in other nuclei. In contrast, orbital and medial cortices, which have a low degree of laminar differentiation, were targeted by the magnocellular subdivision of MD and by numerous other limbic thalamic nuclei, including the midline and the anterior. Thus topographic specificity in the origin of thalamic projections increased as the laminar definition of the target area increased. Moreover, the rostrocaudal distribution of labeled neurons in MD and the medial pulvinar also differed depending on the degree of the laminar definition of the prefrontal target areas. The rostral parts of MD and the medial pulvinar projected to the eulaminate lateral prefrontal cortices, whereas their caudal parts projected to orbital and medial limbic cortices. Selective destruction of caudal MD is known to disrupt mnemonic processes in both humans and monkeys, suggesting that this thalamic-limbic prefrontal loop may constitute an important pathway for memory.

Animals↗

Localization of L-glutamate binding sites in chick brain by quantitative autoradiography.

Quantitative autoradiography was used for the localization of L-[3H]glutamate binding sites in chick brain. The highest concentration of these sites was observed in the molecular layer of cerebellum. High concentrations were also observed in the hippocampus, area parahippocampalis, neostriatum, neostriatum intermedium and hyperstriatum ventrale. In most areas binding of L-[3H]glutamate was increased when incubation was done in chloride-containing medium. This increase was statistically significant in only few of these areas.

Animals↗