Intrinsic circuitry of the amygdaloid complex: common principles of organization in rats and cats.
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Amygdala↗
Biomedical subjects
Y Smith
Publications and source records attributed to Y Smith.
Microcircuitry of the direct and indirect pathways of the basal ganglia.
Our understanding of the organization of the basal ganglia has advanced markedly over the last 10 years, mainly due to increased knowledge of their anatomical, neurochemical and physiological organization. These developments have led to a unifying model of the functional organization of the basal ganglia in both health and disease. The hypothesis is based on the so-called "direct" and "indirect" pathways of the flow of cortical information through the basal ganglia and has profoundly influenced the field of basal ganglia research, providing a framework for anatomical, physiological and clinical studies. The recent introduction of powerful techniques for the analysis of neuronal networks has led to further developments in our understanding of the basal ganglia. The objective of this commentary is to build upon the established model of the basal ganglia connectivity and review new anatomical findings that lead to the refinement of some aspects of the model. Four issues will be discussed. (1) The existence of several routes for the flow of cortical information along "indirect" pathways. (2) The synaptic convergence of information flowing through the "direct" and "indirect" pathways at the single-cell level in the basal ganglia output structures. (3) The convergence of functionally diverse information from the globus pallidus and the ventral pallidum at different levels of the basal ganglia. (4) The interconnections between the two divisions of the pallidal complex and the subthalamic nucleus and the characterization of the neuronal network underlying the indirect pathways. The findings summarized in this commentary confirm and elaborate the models of the direct and indirect pathways of information flow through the basal ganglia and provide a morphological framework for future studies.
Animals↗
Kidney transplantation in recipients with mental retardation: clinical results in a single-center experience.
Mental retardation has been a controversial relative contraindication to organ transplantation. Currently, there are few data available in the literature that describe the outcome of kidney transplantation in mentally retarded patients. In a series of 1,271 kidney transplantations performed between January 1968 and March 1996, we identified eight patients (0.6%) with significant mental retardation (IQ < 70). Only cooperative patients supervised by a reliable long-term caregiver, with long life expectancy, and able to take medication under supervision, were accepted as candidates, independent of the IQ level. At a mean follow-up of 7.3 years, seven patients are alive with functioning grafts, and one lost the kidney to chronic rejection 10 years after transplantation and died of sepsis after resuming dialysis. The 1- and 5-year patient and graft survival are thus 100%. Compliance with immunosuppressive treatment and clinical follow-up was excellent in all of the recipients. The patient quality of life and health were judged by the support persons as highly improved after transplantation in comparison to dialysis. We conclude that kidney transplantation in properly selected patients with mental retardation provides excellent patient and graft survival rates and improves quality of life. In such patients, the presence of mental retardation should not be considered a contraindication to kidney transplantation.
Adolescent↗
Neuronal circuitry and synaptic connectivity of the basal ganglia.
The concept of organization of the basal ganglia has changed markedly over the last 10 years. These developments have led to the introduction of a schematic model of the functional circuitry of the basal ganglia that accounts for normal and abnormal basal ganglia functions. The recent introduction of powerful techniques for the analysis of neuronal networks has led to many new developments in our understanding of the anatomic and synaptic organization of the basal ganglia. The objective of this article is to go from the established model of the basal ganglia connectivity to new anatomic findings that lead to reconsideration and refinement of some aspects of the models.
Basal Ganglia↗
Efferent connections of the internal globus pallidus in the squirrel monkey: I. Topography and synaptic organization of the pallidothalamic projection.
The objectives of this study were, on one hand, to better understand how the segregated functional pathways from the cerebral cortex through the striatopallidal complex emerged in the projections to the thalamus and, on the other hand, to compare the ultrastructure and synaptic organization of the pallidal efferents to the ventrolateral (VL) and centromedian (CM) thalamic nuclei in primates. These aims were achieved by injections of the retrograde-anterograde tracer, biotinylated dextran amine (BDA), in different functional regions of the internal pallidum (GPi) in squirrel monkeys. The location of retrogradely labelled cells in the striatum was determined to ascertain the functional specificity of the injection sites. Injections in the ventrolateral two-thirds of the GPi (group 1) led to retrograde labelling in the postcommissural region of the putamen ("sensorimotor striatum") and plexuses of labelled fibers in the rostral one-third of the principal ventrolateral nucleus (VLp) and the central part of the CM. On the other hand, injections in the dorsal one-third (group 3) and the rostromedial pole (group 4) of the GPi led to retrogradely labelled cells in the body of the caudate nucleus ("associative striatum") and the ventral striatum ("limbic striatum"), respectively. After those injections, dense plexuses of anterogradely labelled varicosities were found in common thalamic nuclei, including the parvocellular ventral anterior nucleus (VApc), the dorsal VL (VLd), and the rostrodorsal part of the parafascicular nucleus (PF). In the caudal two-thirds of the CM/PF, the labelled fibers formed a band that lay along the dorsal border of the complex in a region called the dorsolateral PF (PFdl) in this study. The ventromedial nucleus (VM) was densely labelled only after injections in the rostromedial GPi, whereas the dorsal part of the zona incerta was labelled in both groups. At the electron microscopic level, the BDA-positive terminals in the VLp were larger and more elongated than those in the CM but, overall, displayed the same pattern of synaptic organization. Our findings indicate 1) that some associative and limbic cortical information, which is largely processed in segregated corticostriatopallidal channels, converges to common thalamic nuclei and 2) that the PF is a major target of associative and limbic GPi efferents in monkeys.
Animals↗
Efferent connections of the internal globus pallidus in the squirrel monkey: II. Topography and synaptic organization of pallidal efferents to the pedunculopontine nucleus.
The first objective of the present study was to verify whether projections from regions of the internal pallidum (GPi) that receive inputs from different functional areas of the striatum remain segregated at the level of the pedunculopontine nucleus (PPN) in squirrel monkeys. Second, we analyzed the ultrastructural features and synaptic organization of pallidal terminals in contact with PPN neurons. This was achieved by performing iontophoretic injections of biotinylated dextran amine (BDA) in different regions of the GPi. The animals were pooled into three groups on the basis of the location of the injection sites and the resulting distribution of retrogradely labelled striatal neurons. The experimental groups were divided as follows: group 1: injections in the dorsal one-third of the GPi, retrograde labelling in the head and body of the caudate nucleus ("associative striatum"); group 2: injections in the ventrolateral two-thirds of the GPi, retrograde labelling in the postcommissural region of the putamen ("sensorimotor striatum"); and group 3: injections in the rostromedial pole of the GPi, retrograde labelling in the ventral striatum ("limbic striatum"). These injections led to the anterograde labelling of varicose fibers that arborized profusely in common regions of the PPN dorsal to the brachium conjunctivum. The fields of fibers that arose from the dorsal one-third and the rostromedial pole of the GPi were more widely spread than the afferents from the ventrolateral two-thirds of the GPi. Small numbers of retrogradely labelled cells were encountered in the PPN after each injection in the GPi. Some of them were tightly surrounded by large, BDA-containing varicosities, which implies that the connections between the GPi and the PPN are partly reciprocal. In sections processed for the simultaneous localization of beta-nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase (a marker of cholinergic cells in the PPN) and BDA, the anterogradely labelled fibers largely avoided the dense aggregate of NADPH-diaphorase-containing neurons in the PPN pars compacta (PPNc) but, rather, established contacts with unlabelled neurons in the pars dissipata (PPNd). In the electron microscope, the GPi terminals were large (1.0-5.0 microns in diameter), contained many mitochondria and pleomorphic vesicles, and formed symmetric synapses predominantly with proximal dendrites of PPN cells. In conclusion, our data suggest that the noncholinergic neurons of the PPNd are potential targets for the integration of information arising from different functional territories of the GPi in primates. The PPNd is thus in a position to act as an interface between motivational, cognitive, and motor information transmitted along the pallidotegmental projection in primates.
Acetylcholinesterase↗
Dendrodendritic and axoaxonic synapses in the thalamic reticular nucleus of the adult rat.
Currently, it is believed that cell-cell communications occur in the thalamic reticular nucleus (RT) during thalamocortical operations, but the anatomical substrate underlying these intrinsic interactions has not been characterized fully in the rat yet. To further our knowledge on this issue, we stained juxtacellularly rat RT neurons with biocytin or Neurobiotin and examined their intrinsic axon collaterals and "axon-like processes" at both light and electron microscopic levels. Of 111 tracer-filled RT cells for which the axon could be followed from its origin up to the thalamus, 12 displayed short-range, poorly ramifying varicose local axon collaterals, which remained undistinguishable from parent distal dendrites, raising the question as to whether their varicosities were presynaptic terminals. Correlated light and electron microscopic observations of the proximal part of these intrinsic varicose axonal segments revealed that their varicosities and intervaricose segments were, in fact, postsynaptic structures contacted by a large number of boutons that, for the most, formed asymmetric synapses and were nonimmunoreactive for GABA. Similarly, the so-called "axon-like processes" stemming from the soma or dendrites also were identified as postsynaptic structures. Two unexpected observations were made in the course of this analysis. First, the hillock and initial segment of some RT axons were found to receive asymmetric synaptic inputs from GABA-negative terminals. Second, examination of serial ultrathin sections of dendritic bundles cut in their longitudinal plane revealed the existence of several short symmetric dendrodendritic synapses and numerous puncta adhaerentia between component dendrites. In conclusion, dendrodendritic junctions might be a prominent anatomical substrate underlying interneuronal communications in the RT of the adult rat. Furthermore, excitatory axoaxonic synapses on the axon hillock, initial segment, and local axon collaterals might represent a powerful synaptic drive for synchronizing the firing of RT neurons. Future studies are essential to verify whether excitatory axoaxonic synapses with the axon hillock are a general feature in the RT.
Animals↗
AMPA and NMDA glutamate receptor subunits in midbrain dopaminergic neurons in the squirrel monkey: an immunohistochemical and in situ hybridization study.
The objective of the present study was to analyze the cellular and subcellular localization of ionotropic glutamate receptor subunits in midbrain dopaminergic neurons in the squirrel monkey. This was achieved by means of immunohistochemistry at light and electron microscopic levels and in situ hybridization histochemistry. Colocalization studies show that nearly all dopaminergic neurons in both the ventral and dorsal tiers of the substantia nigra compacta (SNc-v, SNc-d) and the ventral tegmental area (VTA) are immunoreactive for AMPA (GluR1, GluR2/3, and GluR4) and NMDAR1 receptor subunits, but not for NMDAR2A/B subunits. The immunoreactivity of the receptor subunits is associated mainly with perikarya and dendritic shafts. Apart from the intensity of immunolabeling for the GluR4 subunit, which is quite similar for the different groups of midbrain dopaminergic neurons, the overall intensity of immunostaining for the other subunits is higher in the SNc-v and SNc-d than in the VTA. In line with these observations, in situ hybridization shows that the average level of labeling for the GluR2 and NMDAR1 subunit mRNAs is significantly higher in the SNc-v than in the VTA, and for the NMDAR1 subunit, higher in the SNc-v than in the SNc-d. In contrast, no significant difference was found for the level of GluR1 mRNA labeling among the three groups of midbrain dopaminergic neurons. At the subcellular level in the SNc-v, AMPA (GluR1 and GluR2/3) and NMDAR1 receptor subunit immunoreactivity is preferentially associated with the postsynaptic densities of asymmetric synapses, but occasionally some immunoreactivity is found along nonsynaptic portions of plasma membranes of dendrites. A small number of preterminal axons, axon terminals, and glial cell processes are also immunoreactive. Our observations indicate that the different groups of midbrain dopaminergic neurons in primates exhibit a certain degree of heterogeneity with regard to the level of expression of some ionotropic glutamate receptor subunits. The widespread neuronal and glial localization of glutamate receptor subunits suggests that excitatory amino acids may act at different levels to control the basal activity and, possibly, to participate in the degeneration of midbrain dopaminergic neurons in Parkinson's disease.
Animals↗
Ultrastructural localization of CART (cocaine- and amphetamine-regulated transcript) peptides in the nucleus accumbens of monkeys.
CART (cocaine- and amphetamine-regulated transcript) peptides are proposed to play a role in the action of psychostimulants as neurotransmitters/neuromodulators. In the present study, we demonstrate that the shell of the nucleus accumbens, a brain structure involved in drug reinforcement, is densely innervated by a dense plexus of CART peptide-immunoreactive varicose fibers in register with immunoreactive perikarya in monkeys. At the electron microscopic level, varicosities appeared as immunoreactive axon terminals packed with round electron-lucent vesicles and a variable number of darkly stained dense-core vesicles that formed symmetric synapses with dendrites. These findings suggest that CART peptides may be a cotransmitter with gamma aminobutyric acid (GABA) in intrinsic axon collaterals of striatal projection neurons or interneurons in the primate nucleus accumbens.
Animals↗
Effects of ectopic overexpression of p21(WAF1/CIP1) on aneuploidy and the malignant phenotype of human brain tumor cells.
p21WAF1/CIP1 is a downstream effector of the p53 tumor suppressor gene and a universal cyclin-dependent kinase (CDK) inhibitor. To determine the ability of p21WAF1/CIP1 to function as a tumor suppressor, we constructed a replication-defective adenovirus vector containing p21WAF1/CIP1 (Adp21WAF1/CIP1) to effect ectopic overexpression in a p53-defective human astrocytoma cell line, U-373MG. We observed a marked decrease in CDC2 and CDK2 kinase activity associated with a corresponding decrease in the amount of CDC2 but not CDK2 protein; a decreased growth potential of Adp21WAF1/CIP1-infected cells demonstrated by diminished [3H]thymidine incorporation, increased cell doubling time and G1-arrested cell cycle; an association between Adp21WAF1/CIP1-infected cells and inhibition of aneuploid cell accumulation; and an alteration of the malignant phenotype of cells was evidenced by the loss of anchorage-independent growth in soft agar and the failure to induce tumorigenesis in both peripheral and intracerebral xenograft models, including the prevention of tumor formation Adp21WAF1/CIP1 infection 2 days post tumor cell implantation. Adp21WAF1/CIP1. Adp21WAF1/CIP1 appears to be a strong candidate for gene therapy studies based on these studies indicating that Adp21WAF1/CIP1 inhibits proliferation, tumorigenicity and aneuploidy in human brain tumor cells.
Aneuploidy↗
Thalamic collaterals of corticostriatal axons: their termination field and synaptic targets in cats.
Branched cortical projections to the thalamus and striatum were investigated in cats by injecting the retrograde-anterograde tracer biotinylated-dextran amine (BDA) into the caudate nucleus. These injections gave rise to plexuses of labeled fibers and varicosities in widespread thalamic territories. For instance, the lateroposterior nucleus and pulvinar (LP-PUL) mostly contained thick axons that contributed clusters of large-sized varicosities, each forming multiple asymmetric synapses, usually with vesicle-filled dendrites. In contrast, the intralaminar nuclei mostly contained thin axonal segments that emitted small en passant varicosities that formed single asymmetric synapses with spines. Because the caudate nucleus does not project to the thalamus, this labeling had to arise from a neuronal population with branching axons to both structures. Previous findings pointed to three possible sources: brainstem monoaminergic cells, intralaminar thalamic neurons, and corticostriatal cells. The first candidate could be ruled out because monoaminergic neurons contribute small-sized terminals that usually lack membrane specializations. The second possibility was discarded because retrograde tracer injections into the LP-PUL did not give rise to retrograde labeling in the intralaminar nuclear complex but to massive retrograde labeling in deep layers of cortical areas 5 and 7. Therefore, we concluded that the thalamic anterograde labeling originated from corticostriatal neurons, with axons branching to the thalamus. In keeping with this conclusion, Phaseolus vulgaris-leucoagglutinin (PHA-L) injections into cortical areas 5-7 labeled a group of thick corticothalamic fibers that ended in clusters of large boutons in the LP-PUL. These PHA-L-positive terminals were indistinguishable from those labeled after injections of BDA into the caudate nucleus, but they were easy to distinguish from the typical corticothalamic fibers. These findings indicate that the cerebral cortex could coordinate the activity of the striatum and the thalamus via a rich axonal network that collateralizes to both structures. The extent and synaptic organization of this branched projection impose a revision of the traditional scheme of thalamic connectivity.
Animals↗
Differential synaptic innervation of striatofugal neurones projecting to the internal or external segments of the globus pallidus by thalamic afferents in the squirrel monkey.
It is well established that the centromedian nucleus (CM) is the major source of thalamic afferents to the sensorimotor territory of the striatum in monkeys. However, the projection sites of striatal neurons contacted by thalamic afferents still remain to be determined. We therefore carried out an anatomical study aimed at elucidating the hodology of striatal neurones that receive input from the CM in squirrel monkeys. Our approach was to combine the anterograde transport of Phaseolus vulgaris-leucoagglutinin (PHA-L) or biocytin from the CM with the retrograde transport of biotinylated dextran-amine (bio-dex) or PHA-L from the internal (GPi) or external (GPe) segments of the globus pallidus. Following CM injections, rich plexuses of anterogradely labelled, thin varicose fibres aggregated in the form of bands that were confined to the postcommissural region of the putamen. On the other hand, injections into the GPe or GPi led to profuse retrograde labelling of a multitude of medium-sized spiny neurones. In cases where the injections involved the caudoventral two-thirds of the GPe or GPi, the retrogradely labelled striatopallidal cells and the anterogradely labelled thalamostriatal fibres occurred in the sensorimotor territory of the putamen. After injections into either pallidal segments, clusters of retrogradely labelled cells were in register with bands of anterogradely labelled thalamic fibres. However, electron microscopic analysis of striatal regions containing both anterogradely labelled thalamic afferents and retrogradely labelled cells revealed that terminals from the CM frequently form asymmetric synapses with dendritic shafts and spines of striato-GPi cells but rarely with those of striato-GPe cells. In conclusion, our findings demonstrate that thalamic afferents from the CM innervate preferentially striatopallidal neurones projecting to the GPi in monkeys. These results indicate that the striatopallidal neurones contributing to the "direct" and "indirect" output pathways are differentially innervated by thalamic afferents in primates.
Afferent Pathways↗
Synaptic innervation of midbrain dopaminergic neurons by glutamate-enriched terminals in the squirrel monkey.
The excitatory amino acid, glutamate, has long been thought to be a transmitter that plays a major role in the control of the firing pattern of midbrain dopaminergic neurons. The present study was aimed at elucidating the anatomical substrate that underlies the functional interaction between glutamatergic afferents and midbrain dopaminergic neurons in the squirrel monkey. To do this, we combined preembedding immunocytochemistry for tyrosine hydroxylase and calbindin D-28k with postembedding immunostaining for glutamate. On the basis of their ultrastructural features, three types (so-called types I, II, and III) of glutamate-enriched terminals were found to form asymmetric synapses with dendrites and perikarya of midbrain dopaminergic neurons. The type I terminals accounted for more than 70% of the total population of glutamate-enriched boutons in contact with dopaminergic cells in the dorsal and ventral tiers of the substantia nigra pars compacta as well as in the ventral tegmental area, whereas 5-20% of the glutamatergic synapses with dopaminergic neurons involved the two other types of terminals. The major finding of our study is that the glutamate-enriched boutons were involved in 70% of the axodendritic synapses in the ventral tegmental area. In contrast, less than 40% of the boutons in contact with dopaminergic dendrites were immunoreactive for glutamate in the dorsal and ventral tiers of the substantia nigra pars compacta. Approximately 50% of the terminals in contact with the perikarya of the different populations of midbrain dopaminergic neurons displayed glutamate immunoreactivity. In conclusion, our findings provide the first evidence that glutamate-enriched terminals form synapses with midbrain dopaminergic neurons in primates. The fact that the proportion of glutamatergic boutons in contact with dopaminergic cells is higher in the ventral tegmental area than in the substantia nigra pars compacta suggests that the different groups of midbrain dopaminergic neurons are modulated differently by extrinsic glutamatergic afferents in primates.
Animals↗
Glutamatergic inputs from the pedunculopontine nucleus to midbrain dopaminergic neurons in primates: Phaseolus vulgaris-leucoagglutinin anterograde labeling combined with postembedding glutamate and GABA immunohistochemistry.
To verify the possibility that the pedunculopontine nucleus is a source of glutamatergic terminals in contact with midbrain dopaminergic neurons in the squirrel monkey, we used the anterograde transport of Phaseolus vulgaris-leucoagglutinin in combination with preembedding immunohistochemistry for tyrosine hydroxylase and for calbindin D-28k and postembedding immunocytochemistry for glutamate and for gamma-aminobutyric acid. Following tracer injections in the pedunculopontine nucleus, numerous anterogradely labeled fibers emerged from the injection sites to innervate densely the pars compacta of the substantia nigra and ventral tegmental area. The major type of labeled fibers were thin with multiple collaterals and varicosities that established intimate contacts with midbrain dopaminergic neurons. At the electron microscopic level, the anterogradely labeled boutons were medium sized (maximum diameter between 0.9 microns and 2.5 microns) and contained numerous round vesicles and mitochondria. Postembedding immunocytochemistry revealed that 40-60% of anterogradely labeled terminals were enriched in glutamate and formed asymmetric synapses with dendritic shafts of substantia nigra and ventral tegmental area neurons. In triple-immunostained sections, some of the postsynaptic targets to these terminals were found to be dopaminergic. In addition, 30-40% of the anterogradely labeled terminals in both regions displayed immunoreactivity for gamma-aminobutyric acid and, in some cases, formed symmetric synapses with dendritic shafts. In conclusion, our results provide the first ultrastructural evidence for the existence of synaptic contacts between glutamate-enriched terminals from the pedunculopontine nucleus and midbrain dopaminergic neurons in primates. Our results also show that the pedunculopontine nucleus is a potential source of gamma-aminobutyric acid input to this region. These findings suggest that the pedunculopontine nucleus may play an important role in the modulation of the activity of midbrain dopaminergic cells by releasing glutamate or gamma-aminobutyric acid as neurotransmitter.
Animals↗
The subthalamic nucleus and the external pallidum: two tightly interconnected structures that control the output of the basal ganglia in the monkey.
The aim of the present study was to elucidate the organization of the interconnections between the subthalamic nucleus and the two segments of the globus pallidus in squirrel monkeys. By making small deposits of tracers in the two segments of the globus pallidus, we demonstrate that interconnected neurons of the subthalamic nucleus and the external pallidum innervate, via axon collaterals, the same population of neurons in the internal pallidum. Furthermore, this organizational principle holds true for different functional regions of the pallidum and the subthalamic nucleus. Injections of biotinylated dextran amine were made in the dorsal (associative), ventrolateral (sensorimotor) and rostromedial (limbic) regions of the internal pallidum. Following these injections, there were rich clusters of labelled terminals in register with retrogradely labelled perikarya in related functional regions of the subthalamic nucleus and the external pallidum. At the electron microscopic level, the majority of labelled terminals in the external pallidum displayed the ultrastructural features of boutons from the subthalamic nucleus and were non-immunoreactive for GABA, whereas those in the subthalamic nucleus resembled terminals from the external pallidum and displayed GABA immunoreactivity. In both cases, the synaptic targets of the labelled terminals included labelled neurons. These observations suggest that the biotinylated dextran amine injected in the internal globus pallidus was transported retrogradely to perikarya in the external pallidum and the subthalamic nucleus and then anterogradely, via axon collaterals, to the subthalamic nucleus and the external pallidum respectively. This suggestion was supported by injections of biotinylated dextran amine or Phaseolus vulgaris-leucoagglutinin in regions of the external pallidum that corresponded to those containing retrogradely labelled cells following injections in the internal pallidum. The clusters of labelled cells and varicosities that resulted from these injections were found in regions of the subthalamic nucleus similar to those labelled following injections in the internal globus pallidus. Furthermore, terminals from the external pallidum and the subthalamic nucleus converged on the same regions in the internal globus pallidus. The results of the present tracing study define the basic network underlying the interconnections between the external segment of the globus pallidus and the subthalamic nucleus, and their connections with the output neurons of the basal ganglia in primates.
Animals↗
Differential localization of AMPA glutamate receptor subunits in the two segments of the globus pallidus and the substantia nigra pars reticulata in the squirrel monkey.
The subthalamic nucleus has long been known as the main source of glutamatergic afferents to the pallidum and the substantia nigra in primates. Recent findings showed that the excitatory effects induced by the subthalamic nucleus in pallidal cells are mediated through the activation of non-NMDA receptors in the rat. The objective of the present study was to analyse the distribution of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) glutamate receptor subunits in the external pallidum (GPe), the internal pallidum (GPi) and the substantia nigra pars reticulata (SNr) in squirrel monkeys (Saimiri sciureus). This was achieved by means of immunohistochemistry using antibodies raised against the GluR1 and the GluR2/3 subunits of the AMPA receptor. Our results show that all neuronal perikarya in GPe and GPi display immunoreactivity for GluR2/3 subunits whereas GluR1 is confined exclusively to cells in the GPe. The proportion of GluR1-immunoreactive neurons is not uniform throughout the rostrocaudal extent of GPe; in the rostral third all GPe cells display GluR1 immunoreactivity, whereas in the caudal third the proportion of GluR1-positive cells decreases to 50%. The intensity of GluR1 immunostaining associated with GPe cells is lower than that associated with neighbouring large-sized neurons in the nucleus basalis of Meynert. In contrast to GPi cells, the neurons in the SNr display immunoreactivity for both GluR1 and GluR2/3 subunits. In conclusion, our results provide the first evidence for a different distribution of the GluR1 subunit of the AMPA receptors in the two segments of the globus pallidus in monkeys. These findings imply that the control of the basal activity of GPe and GPi cells by the subthalamic nucleus is exerted via the activation of AMPA receptors composed of different subunits. These data reinforce the view that the two segments of the globus pallidus are different entities that possess their own functional characteristics in primates.
Afferent Pathways↗
Differential synaptic innervation of neurons in the internal and external segments of the globus pallidus by the GABA- and glutamate-containing terminals in the squirrel monkey.
The present study aimed at comparing the pattern of synaptic innervation of neurons in the external (GPe) and internal (GPi) pallidum by gamma-aminobutyric acid (GABA)- and glutamate-immunoreactive terminals in the squirrel monkey. Four major populations of terminals were encountered in GPe and GPi. Our findings combined with those obtained in previous tract-tracing studies reveal that the synaptic innervation of perikarya in GPe is strikingly different from that in GPi. Although the GABA-positive type I boutons (from the striatum) represent 85% of the terminals in contact with somata in GPe, only 32% of the axosomatic synapses involve this type of terminal in GPi. However, the type II terminals (from GPe), which display a moderate level of GABA and glutamate immunoreactivities, account for 48% of the boutons in contact with perikarya in GPi but only 10% in GPe. In both pallidal segments, less than 10% of the axosomatic synapses involve the glutamate-immunoreactive type III terminals (from the subthalamic nucleus). Finally, the type IIa boutons (unknown source), which show levels of immunoreactivities similar to the type II terminals, account for 12% of the boutons in contact with perikarya in GPi but only 4% in GPe. In contrast to perikarya, the innervation of dendritic shafts is similar in both GPe and GPi; more than 80% of the axodendritic synapses involve the type I terminals, 10-15% involve the type III terminals, less than 5% are formed by the type II boutons, and less than 1% involve the type IIa terminals. Three other categories of boutons (types IV, V, VI) account for less than 1% of the total population of terminals in GPe and GPi. In conclusion, our findings demonstrate a differential synaptic innervation of neuronal perikarya in GPe and GPi in primates. These data suggest that the two pallidal segments are separate functional entities of which the neuronal activity is largely controlled by extrinsic inputs that are differentially distributed at the level of single cells.
Animals↗
Intra-amygdaloid projections of the basolateral and basomedial nuclei in the cat: Phaseolus vulgaris-leucoagglutinin anterograde tracing at the light and electron microscopic level.
The amygdaloid complex plays an essential role in auditory fear conditioning of the Pavlovian type. The available evidence suggests that the lateral nucleus is the input station of the amygdala for auditory conditioned stimuli, whereas the central medial nucleus is the output for conditioned fear responses. However, the intrinsic pathway transmitting auditory information about the conditioned stimulus from the lateral to the central medial nuclei is unknown as there are no direct projections between these nuclei. The present study was undertaken to determine if the main intra-amygdaloid targets of the lateral nucleus, namely the basomedial and basolateral nuclei, project to the central medial nucleus. To this end, iontophoretic injections of the anterograde tracer Phaseolus vulgaris-leucoagglutinin were performed in these nuclei. To rule out the possibility that the anterograde labeling reflected passing fibers merging with the major fiber bundles that course in and around the central medial nucleus, labeled terminals and varicosities were observed in the electron microscope. It was determined that the basolateral and basomedial nuclei have partially overlapping intraamygdaloid targets. They both project to the central medial nucleus, nucleus of the lateral olfactory tract and peri-amygdaloid cortex, but have limited projections to each other. Small Phaseolus vulgaris-leucoagglutinin injections in both nuclei gave rise to prominent intranuclear projections but only the basomedial nucleus was found to project to the lateral and anterior cortical nuclei. At the electron microscopic level, all labeled axon terminals and varicosities formed asymmetric synapses (n = 245) with dendritic spines (83%) or with dendritic shafts (17%). This is the first unambiguous demonstration that the basolateral and basomedial nuclei project to the central medial nucleus. Since these nuclei constitute the main intra-amygdaloid targets of the lateral nucleus, they represent likely candidates for the transmission of auditory conditioned stimuli to the central medial nucleus in auditory fear conditioning.
Amygdala↗