PubMed Health⌕ Search

Biomedical subjects

C R Gerfen

Publications and source records attributed to C R Gerfen.

69 records · Page 4Linked to original sources
PubMed1985

The neostriatal mosaic. I. Compartmental organization of projections from the striatum to the substantia nigra in the rat.

Combined neuroanatomical techniques were used to examine the organization of the striatal projection to the substantia nigra in the rat. Both double anterograde axonal tracing methods (Phaseolus vulgaris leuco-agglutinin (PHA-L) and 3H-amino acid tract tracing) and double fluorescent retrograde axonal transport tracing methods were used to examine the relationship among striatal neurons projecting to separate areas of the substantia nigra. Additionally, the distributions of retrogradely labeled striatonigral projection neurons were charted relative to the neurochemically distinct striatal "patch" compartment, identified by substance P- or leu-enkephalin-like immunoreactivity, and the complementary "matrix" compartment, identified by somatostatin-like immunoreactive fibers. These studies show two distinct types of organization in the striatonigral projections. One type is topographic in that the mediolateral relationships among these striatal efferent neurons are roughly maintained by their termination patterns in the substantia nigra, while the dorsoventral relationships are inverted. Projections from any part of the striatum, however, are distributed throughout the rostrocaudal axis of the substantia nigra. Despite their general topographic organization, the variable and dispersed nature of such projections from individual striatal loci results in partial overlap of afferent fields from separate striatal areas. The second type of organization is nontopographic and provides a different system for convergence of inputs from separated striatal areas that is superimposed on the rough topographic system. In this other projection system the mediolateral and dorsoventral relationships typical of the topographically ordered system are not maintained and are sometimes reversed. For example, PHA-L injected into the dorsal striatum labels a topographic (inverted relationship) projection to the ventral substantia nigra pars reticulata but also a smaller and separate projection to the dorsal pars reticulata and adjacent pars compacta. Retrograde tracer deposits in the pars compacta label neurons in the ventral striatum (the inverted relationship) but also clusters of neurons in the dorsal striatum. These clusters are in the neurochemically defined patch compartment whereas neurons in the matrix are labeled by injections into the pars reticulata. The dendrites of both retrogradely filled patch and matrix neurons are confined to the compartment containing their cell bodies, suggesting a restriction that would functionally segregate extrinsic striatal afferents shown in other studies to be confined to either patches or matrix.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

The neostriatal mosaic: compartmental distribution of calcium-binding protein and parvalbumin in the basal ganglia of the rat and monkey.

Calcium-binding protein (CaBP) and parvalbumin are two proteins that are expressed in brain and bind calcium in the micromolar range. The immunohistochemical distribution of these two proteins was examined in the basal ganglia of rats and rhesus monkeys. In the striatum, CaBP immunoreactivity is localized to a subset of striatonigral projection neurons; CaBP-positive neurons are distributed in areas containing somatostatin-immunoreactive fibers and not in the complementary areas containing dense mu opiate-receptor binding. These biochemical labels mark, respectively, the matrix and patch compartments of the striatum. Previous studies have shown that striatal matrix neurons project to the substantia nigra pars reticulata, whereas striatal patch neurons project to the substantia nigra pars compacta. Consistent with the restricted localization of CaBP in the matrix projection neurons is the confinement of CaBP-immunoreactive afferent fibers to the pars reticulata. CaBP is also localized to a portion of dopaminergic and a few nondopaminergic neurons in the substantia nigra pars compacta and in most dopaminergic neurons in the ventral tegmental area. Parvalbumin immunoreactivity is localized to a subset of substantia nigra pars reticulata neurons and their axons. In the lateral striatum, some medium-sized aspiny interneurons are also parvalbumin immunoreactive. The distinct distributions of CaBP and parvalbumin in the basal ganglia are discussed in terms of their possible roles as intracellular calcium buffer systems related to the physiologic response properties of the neurons in which they are contained.

Animals↗
PubMed1984

The organization of projections from the cortex, amygdala, and hypothalamus to the nucleus of the solitary tract in rat.

Direct projections from the forebrain to the nucleus of the solitary tract (NTS) and dorsal motor nucleus of the vagus in the rat medulla were mapped in detail using both retrograde axonal transport of the fluorescent tracer True Blue and anterograde axonal transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). In the retrograde tracing studies, cell groups in the medial prefrontal cortex, lateral prefrontal cortex (primarily ventral and posterior agranular insular cortex), bed nucleus of the stria terminalis, central nucleus of the amygdala, paraventricular, arcuate, and posterolateral areas of the hypothalamus were shown to project to the NTS and in some cases also to the dorsal motor nucleus of the vagus. The prefrontal cortical areas projecting to the NTS apparently overlap to a large degree with those cortical areas receiving mediodorsal thalamic and dopaminergic input. The retrogradely labeled cortical cells were situated in deep layers of the rat prefrontal cortex. The anterograde tracing studies revealed a prominent topography in the mediolateral termination pattern of forebrain projections to the rostral part of the NTS and to the dorsal pons. The projections to the NTS were generally bilateral, except for projections from the central nucleus of the amygdala and bed nucleus of the stria terminalis which were predominantly ipsilateral. The prefrontal cortical projections to the NTS travel through the cerebral peduncle and pyramidal tract and terminate throughout the rostrocaudal extent of the NTS. Specifically, the prefrontal cortex innervates dorsal portions of the NTS (lateral part of the dorsal division of the medial solitary nucleus, dorsal part of the lateral solitary nucleus and the caudal midline region of the commissural nucleus), areas which receive relatively sparse subcortical projections. These dorsal portions of the NTS receive major primary afferent projections from the vagal and glossopharyngeal nerves. In contrast, the subcortical projections, which travel through the midbrain and pontine tegmentum, terminate most heavily in the ventral portions of the NTS, i.e., the area immediately dorsal and lateral to the dorsal motor nucleus of the vagus. Only the paraventricular hypothalamic nucleus has substantial terminals throughout the dorsal motor nucleus of the vagus. Hypothalamic cell groups innervate the area postrema and, along with the prefrontal cortex, innervate the zone subjacent to the area postrema.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗
PubMed1984

Evidence for a projection from the lateral preoptic area and substantia innominata to the 'mesencephalic locomotor region' in the rat.

A series of anatomical and electrophysiological experiments have been carried out to examine the organization of a direct projection from the substantia innominata and the lateral preoptic area of the hypothalamus, referred to collectively as the subpallidal region, to the pedunculopontine nucleus and adjacent parts of the dorsal midbrain in the adult rat. In the first series of experiments, the retrogradely transported fluorescent tracer SITS, which does not appear to be taken up by fibers-of-passage, was injected into the pedunculopontine nucleus, and the distribution of labeled neurons was plotted in the substantia innominata and lateral preoptic area, as well as in adjacent regions including the medial preoptic area, the bed nucleus of the stria terminalis and parvocellular parts of the paraventricular nucleus. Then, the anterogradely transported lectin PHA-L, which also does not appear to be taken up in effective amounts by fibers-of-passage, was injected into parts of the substantia innominata and lateral preoptic area that project directly to the pedunculopontine nucleus. These experiments demonstrated that fibers from both regions descend through the medial forebrain bundle and give rise in the pedunculopontine nucleus to a terminal field that contains many structures with the appearance of terminal boutons. They also indicated that individual fibers from the subpallidal region innervate both the pedunculopontine nucleus and adjacent parts of the central gray, and that the pathway innervates areas along the length of the medial forebrain bundle on its way to the dorsal midbrain. In a third series of experiments the retrogradely transported fluorescent tracer True Blue was injected into upper thoracic levels of the spinal cord, and it was found that the region of the pedunculopontine nucleus that receives the densest input from the subpallidal region contained many retrogradely labeled neurons on both sides of the brain. And finally, a series of electrophysiological experiments demonstrated that single-pulse stimulation of the substantia innominata and the lateral preoptic area altered the firing rate of a majority of the neurons in and around the pedunculopontine nucleus, and that excitatory and inhibitory responses occurred about equally. These results clearly suggest that the subpallidal region projects directly to the pedunculopontine nucleus and adjacent regions including the central gray and the superior colliculus.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗
PubMed1984

An anterograde neuroanatomical tracing method that shows the detailed morphology of neurons, their axons and terminals: immunohistochemical localization of an axonally transported plant lectin, Phaseolus vulgaris leucoagglutinin (PHA-L).

A new neuroanatomical method for tracing connections in the central nervous system based on the anterograde axonal transport of the kidney bean lectin, Phaseolus vulgaris-leucoagglutinin (PHA-L) is described. The method, for which a detailed protocol is presented, offers several advantages over present techniques. First, when the lectin is delivered iontophoretically, PHA-L injection sites as small as 50-200 micron in diameter can be produced, and are clearly demarcated since the neurons within the labeled zone are completely filled. Second, many morphological features of such filled neurons are clearly demonstrated including their cell bodies, axons, dendritic arbors and even dendritic spines. Third, there is some evidence to suggest that only the neurons at the injection site that are filled transport demonstrable amounts of the tracer, raising the possibility that the effective injection site can be defined quite precisely. Fourth, even with the most restricted injections, the morphology of the labeled axons and axon terminals is clearly demonstrated; this includes boutons en passant, fine collateral branches, and various terminal specializations, all of which can be visualized as well as in the best rapid Golgi preparations. Fifth, when introduced iontophoretically, PHA-L appears to be transported preferentially in the anterograde direction; only rarely is it transported retrogradely. Sixth, PHA-L does not appear to be taken up and transported effectively by fibers of passage. Seventh, there is no discernible degradation of the transported PHA-L with survival times of up to 17 days. Finally, since the transported marker can be demonstrated with either peroxidase or fluorescent antibody techniques, it may be used in conjunction with other neuroanatomical methods. For example, double anterograde labeling experiments can be done using the autoradiographic method along with immunoperoxidase localization of PHA-L, and the retrogradely transported fluorescent dyes can be visualized in the same tissue sections as PHA-L localized with immunofluorescence techniques.

Animals↗
PubMed1983

The development and restriction of the ipsilateral retinofugal projection in the chick.

Although it is generally believed that the central projections of the retina in birds are entirely crossed, using wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) as an anterograde tracer, we have found that in normal posthatched chicks there is a small ipsilateral retinofugal projection to the diencephalon and midbrain. Most of the ipsilateral fibers appear to be directed to the lateral anterior and dorsolateral anterior nuclei of the thalamus, to the pretectal region, and to the ectomammillary nucleus and the adjoining nucleus externus. Even in the best preparations the numbers of ipsilateral fibers are so small that it is hardly surprising that they have been overlooked in previous axonal degeneration and autoradiographic experiments. A significantly larger ipsilateral retinal projection develops during the second week of incubation. The ipsilaterally directed fibers can be first seen on the fifth day of incubation and their numbers appear to increase until about embryonic day 12. At this stage the projection involves substantially more fibers than at hatching and is also more extensive in its distribution; in fact, in its general organization (but not its size) it closely parallels the normal crossed retinofugal system, contributing fibers to essentially all the primary visual relay nuclei in the diencephalon and midbrain and to much of the optic tectum, where the densest projection is to its caudomedial aspect. During the second week of incubation there is also a small number of retinal fibers, which after crossing in the optic chiasm, recross the midline in the posterior and tectal commissures (and also in the tectal roof plate), before ending in the pretectal region of the ipsilateral side. In addition, there is a markedly aberrant projection from the retina into the contralateral optic nerve. Most of the ipsilateral retinal fibers are eliminated between the twelfth and sixteenth days of incubation, and by day 17 the ipsilateral projection is reduced to its mature form. The progressive reduction in the ipsilateral projection occurs at a time when it is known (from other studies) that there is an appreciable loss of retinal ganglion cells; but whether the reduction is due to neuronal death or to the selective elimination of ipsilateral axon collaterals remains to be determined. The existence of a significant ipsilateral retinofugal component early in development, probably accounts, in part, for the distinctive and persistent ipsilateral projection that occurs if one eye is removed during the first few days of incubation.

Animals↗
PubMed1982

Crossed connections of the substantia nigra in the rat.

The existence of crossed multisynaptic pathways that allow for the interdependent control of activity in one substantia nigra and its contralateral counterpart has been inferred from a number of recent biochemical and neurophysiological investigations. This prompted a reexamination of the connections of the substantia nigra with an emphasis on crossed inputs to and crossed projections from that nucleus. Male albino rats received 20-50-nl pressure injections of a 1% wheat germ agglutinin-conjugated horse-radish peroxidase (WGA-HRP) solution into the substantia nigra or into surrounding areas as controls. Following a 24-hour survival period the animals were processed according to the tetramethylbenzidine protocol for the visualization of HRP. The pattern of anterograde transport of WGA-HRP after substantia nigra injections, confirming for the most part previous reports, demonstrated ipsilateral nigral efferent projections to the striatum; globus pallidus; subthalamic nucleus; the lateral dorsal, paralamellar mediodorsal, ventromedial, and parafascicular thalamic nuclei; central gray, midbrain reticular formation; superior colliculus; and peribrachial area, including the pedunculopontine nucleus. Additionally, the nigral projections to the paralamellar mediodorsal and ventromedial thalamic nuclei and to the superior colliculus were demonstrated to be bilateral. Most of these connections were confirmed by the complementary retrograde experiment. In accordance with previous reports, intranigral WGA-HRP injections retrogradely labeled neurons located in the ipsilateral prefontal cortex, motor cortex, striatum, globus pallidus, central nucleus of the amygdala, anterior hypothalamic area, subthalamic nucleus, and dorsal raphe. Additionally, labeled perikarya were observed in the ipsilateral parafascicular thalamic nucleus, in the contralateral posterior lateral hypothalamic area, and in the ipsilateral and contralateral peribrachial-pedunculopontine area. These latter nigral afferents were confirmed with complementary WGA-HRP injections into each of the regions of origin. While bilateral peribrachial-pedunculopontine innervation of the substantia nigra has been reported in the cat there has been no previous demonstration of a crossed nigral afferent system from the contralateral posterior lateral hypothalamic area. The results are discussed with reference to the pathways that may mediate the interdependent control of the activity of neurons in the left and right substantia nigra. Additionally, the association of the substantia nigra with a variety of neuronal circuits, including the cerebellofugal, tectothalamic, thalamocortical, thalamostriatal, and basal ganglia pathways, are discussed.

Animals↗
PubMed1982

A note on the transneuronal transport of wheat germ agglutinin-conjugated horseradish peroxidase in the avian and rodent visual systems.

While using horseradish peroxidase conjugated to the plant lectin wheat germ agglutinin (WGA-HRP) as an anterograde marker to label the developing retinofugal projection in the chick, we have found that a significant amount of the tracer can escape from the axons and axon terminals of retinal ganglion cells and be subsequently taken up and transported both anterogradely and retrogradely by neighboring neurons and/or axon terminals. The release and uptake of the tracer appears to be nonspecific, and is particularly striking at embryonic stages; at these stages there is also appreciable uptake of the WGA-HRP by ependymal cells and by radial glial processes. Subsequent experiments in rats have shown that as early as 2 days after an injection of WGA-HRP into an eye there is clear labeling of geniculo-cortical axons in the striate cortex. Since WGA-HRP is being used increasingly in neuroanatomical studies, it is now clear that when interpreting the results of experiments with this marker the possibility of transneuronal labeling must be borne in mind, and especially after relatively long post-labeling survival periods. At the same time the secondary transport of WGA-HRP may, in certain neural systems, provide a useful tool for analyzing second-order connections.

Age Factors↗
PubMed1982

Intracranial self-stimulation in the thalamus of the rat.

Rats were tested for intracranial self-stimulation (ICSS) via bipolar electrodes situated throughout the thalamus. Of 112 animals in the study, 55 met the criteria for ICSS, with scores ranging from 55 to 921 bar-presses in a 15 minute session. A map of both positive and neutral placements is presented. Positive sites for ICSS were found in all aspects of the mediodorsal nucleus, except for the central segment. The ventromedial nuclear complex was also a positive area of ICSS, with the exception of the submedial nucleus (nucleus gelatinosus). Each of the intralaminar nuclei (central medial, parafascicular, paracentral, and central lateral) supported ICSS, as did each of the midline nuclei (rhomboid, paratenial and paraventricular). No placements were found in the nucleus reuniens. Both "major" relay nuclei, the ventrobasal and ventrolateral, supported ICSS; but neither the laterodorsal nor the lateral posterior nuclei had positive caudal thalamus. As a general rule, ICSS scores appeared to be higher as the electrode placements approached the midline. Sites in which no positive placements were seen included the reticular nucleus, as well as the stria medularis, the mammillothalamic tract, and the fasciculus retroflexus.

Animals↗
PubMed1981

Intracranial self-stimulation from the sulcal prefrontal cortex in the rat: the effect of 6-hydroxydopamine or kainic acid lesions at the site of stimulation.

An electrode cannula system was used to elicit intracranial self-stimulation (ICSS) from the sulcal prefrontal cortex in rats to test the behavioral effects of local infusions of 6-hydroxydopamine (6-OHDA) or kainic acid (KA) into the brain area surrounding the electrode tip. In experiment I sulcal ICSS animals received injections of 6-OHDA with or without desipramine (DMI) pretreatment to block 6-OHDA uptake into noradrenergic (NA) terminals. Those animals that received DMI pretreatment were subsequently shown to have sustained sulcal cortical dopaminergic (DA) denervation while sulcal molecular layer NA systems were spared as revealed with glyoxylic acid-induced catecholamine histofluorescence. Those animals not receiving DMI pretreatment sustained near-complete denervation of both NA and DA sulcal cortical systems. Neither treatment had a lasting effect on sulcal ICSS suggesting that sulcal ICSS is not dependent on the presynaptic release or DA of NA into that brain area. In experiment II KA injections that lesioned neurons in sulcal cortical layers V and VI resulted in the abolition of sulcal ICSS for the duration of a 21 day postlesion trial period. These results suggest that activation of a descending corticofugal system originating in the sulcal cortex is responsible for the mediation of sulcal prefrontal cortical ICSS. This system was mapped by the selective silver impregnation of degenerating neural elements resulting from effective lesions.

Animals↗
PubMed1979

Self-stimulation of the sulcal prefrontal cortex in the rat: direct evidence for ascending dopaminergic mediation.

Intracranial self-stimulation (ICSS) of the prefrontal cortex dorsal to the rhinal sulcus in rats has been abolished by means of injections of 6-hydroxydopamine (6-OHDA) (4 micrograms/2 microliters) into the ascending trajectory of the A10 mesocortical dopaminergic fibers ipsilateral to the stimulation electrodes. Similar injections made contralateral to the stimulation electrodes produced a transient attenuation of this self-stimulation. All cases of such lesions were confirmed with the use of Vibratome histochemical fluorescence examination of each of the dopamine projection areas in the forebrain.

Animals↗
PubMedDate not supplied

Neural inputs to the prefrontal agranular insular cortex in the rat: horseradish peroxidase study.

The prefrontal cortex, dorsal to the rhinal sulcus of the rat (hereinafter termed the agranular insular cortex) has been examined with the use of the retrograde transport of horseradish peroxidase. Labelled perikarya were seen in the region of the ipsilateral medial forebrain bundle, consistently rostral to the caudal edge of the posterior mammillary nucleus. These cells were interpreted as being the rostral members of the A10 dopaminergic cell group. Labelled cells were also seen in the dorsal raphe nucleus, the ipsilateral pyriform cortex, the contralateral agranular insular cortex, the ipsilateral basolateral amygdaloid nucleus, the ipsilateral locus coeruleus, and the medio-dorsal, ventromedial, and parafascicular thalamic nuclei. Detailed examination of the thalamic input confirmed a differential innervation of the dorsal and ventral regions of the agranular insular cortex. Possible functional correlates of these prefrontal afferents are discussed.

Afferent Pathways↗
PubMedDate not supplied

The neostriatal mosaic: compartmentalization of corticostriatal input and striatonigral output systems.

The striatum (caudate-putamen) of the basal ganglia in the mammalian forebrain is a mosaic of two interdigitating, neurochemically distinct compartments. One type, the 'patch' compartment, is identified by patches of dense opiate receptor binding, and is enriched in enkephalin- and substance P-like immunoreactivity. The other compartment, the 'matrix', has a high acetylcholinesterase activity, and is shown here to have a dense plexus of fibres displaying somatostatin-like immunoreactivity. The present study demonstrates the two compartments have distinct connections, using a method that concurrently reveals striatal input, output and neurochemical systems in the rat. Patches receive inputs from the prelimbic cortex (a medial frontal cortical area with direct 'limbic' inputs from the amygdala and hippocampus); they also project to the substantia nigra pars compacta (the source of the nigrostriatal dopaminergic system). Conversely, the matrix receives inputs from sensory and motor cortical areas; here it is shown to project to the substantia nigra pars reticulata (the source of the non-dopaminergic nigrothalamic and nigrotectal system). Also, an intrinsic striatal somatostatin-immunoreactive system is described that may provide a link between the two compartments. The striatal patch and matrix compartments thus appear to be functionally distinct and interactive parallel input-output processing channels.

Afferent Pathways↗
PubMedDate not supplied

Multiple D2 dopamine receptors produced by alternative RNA splicing.

Dopamine receptor belong to a large class of neurotransmitter and hormone receptors that are linked to their signal transduction pathways through guanine nucleotide binding regulatory proteins (G proteins). Pharmacological, biochemical and physiological criteria have been used to define two subcategories of dopamine receptors referred to as D1 and D2. D1 receptors activate adenylyl cyclase and are coupled with the Gs regulatory protein. By contrast, activation of D2 receptors results in various responses including inhibition of adenylyl cyclase, inhibition of phosphatidylinositol turnover, increase in K+ channel activity and inhibition of Ca2+ mobilization. The G protein(s) linking the D2 receptors to these responses have not been identified, although D2 receptors have been shown to both copurify and functionally reconstitute with both Gi and Go related proteins. The diversity of responses elicited by D2-receptor activation could reflect the existence of multiple D2 receptor subtypes, the identification of which is facilitated by the recent cloning of a complementary DNA encoding a rat D2 receptor. This receptor exhibits considerable amino-acid homology with other members of the G protein-coupled receptor superfamily. Here we report the identification and cloning of a cDNA encoding an RNA splice variant of the rat D2 receptor cDNA. This cDNA codes for a receptor isoform which is predominantly expressed in the brain and contains an additional 29 amino acids in the third cytoplasmic loop, a region believed to be involved in G protein coupling.

Amino Acid Sequence↗