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J H Fallon

Publications and source records attributed to J H Fallon.

At least 55 records · Page 3Linked to original sources

A retino-mesotelencephalic pathway in the rat.

We have demonstrated a disynaptic pathway in the adult rat that connects retinal ganglion cells with the anteromedial portion of the caudate-putamen and with the prefrontal and anterior cingulate cortex through the ventral midbrain tegmentum. This retino-mesotelencephalic pathway has been revealed by double-labeling methods in which neurons located in the medial portion of the pars compacta of the substantia nigra and the lateral portion of the nucleus paranigralis of the ventral tegemental area have been retrogradely labeled with tracers injected into the anteromedial portion of the caudate-putamen or the prefrontal/anterior cingulate cortex and have been anterogradely, and transynaptically, labeled with [3H]adenosine injected into the eye. The data show a disynaptic connection from retinal ganglion cells to striatal and cortical neurons by which direction and velocity specific visual information may affect visually guided motor behavior.

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GABAergic neurons comprise a major cell type in rodent visual relay nuclei: an immunocytochemical study of pretectal and accessory optic nuclei.

The enzyme glutamic acid decarboxylase (GAD) has been localized in sections of rodent brains (gerbil, rat) using conventional immunocytochemical techniques. Our findings demonstrate that large numbers of GAD-positive neurons and axon terminals (puncta) are present in the visual relay nuclei of the pretectum and the accessory optic system. The areas of highest density of these neurons are in the nucleus of the optic tract (NOT) of the pretectum, the dorsal and lateral terminal accessory optic nuclei (DTN, LTN), the ventral and dorsal subdivisions of the medial terminal accessory optic nucleus (MTNv, MTNd), and the interstitial nucleus of the posterior fibers of the superior fasciculus (inSFp). The findings indicate that 27% of the NOT neurons are GAD-positive and that these neurons are distributed over all of the NOT except the most superficial portion of the NOT caudally. The GAD-positive neurons of the NOT are statistically smaller (65.9 microns2) than the total population of neurons of the NOT (84.3 microns2) but are otherwise indistinguishable in shape from the total neuron population. The other visual relay nuclei that have been analyzed (DTN, LTN, MTNv, MTNd, inSFp) are similar in that from 21% to 31% of their neurons are GAD-positive; these neurons are smaller in diameter and are more spherical than the total populations of neurons. The data further show that a large proportion of the neurons in these visual relay nuclei are contacted by GAD-positive axon terminals. It is estimated that approximately one-half of the neurons of the NOT and the terminal accessory optic nuclei receive a strong GABAergic input and have been called "GAD-recipient neurons". Further, the morphology of the GAD-positive neurons combined with their similar distribution to the GAD-recipient neurons suggest that many of these neurons are acting as GABAergic, local circuit neurons. On the other hand, the large number of GAD-positive neurons in the NOT and MTN (20-30%) in relation to estimates of projection neurons (75%) presents the possibility that some may in fact be projection neurons. The overall findings provide morphological evidence which supports the general conclusion that GABAergic neurons play a significant role in modulating the output of the visually related NOT and terminal accessory optic nuclei.

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Few cortical cholecystokinin immunoreactive neurons have long projections.

Cholecystokinin (CCK)-like immunoreactive neurons have been reported to be widely distributed throughout both the neo- and allocortices. In the present study, we were interested in determining whether these cortical CCK neurons have long projections using the double-labeling technique of fluorescence retrograde tracing combined with immunofluorescence for CCK. The distribution of CCK immunoreactive perikarya and fibers was plotted throughout the rostro-caudal extent of the cerebral cortex in both untreated and colchicine-treated albino rats. In the double-labeling experiments, the animals received injections of fluorescent retrograde tracers into cortical, limbic, striatal or thalamic structures, followed one to two days later by colchicine treatment. Brains were subsequently processed for indirect immunofluorescence for CCK-octapeptide and fluorescent dye localization. It was found that 1) a small number of prefrontal cortical CCK neurons were double-labeled with both fluorescent dye and immunofluorescence for CCK after dye injection into midline thalamus, 2) only rarely were cortical CCK neurons double-labeled with injection of tracers into cortex, striatum, or other subcortical structures, 3) numerous midbrain CCK neurons were double-labeled after dye injection into prefrontal cortex and anterior cingulate cortex. and 4) colchicine or cannula injection damage to cortical forebrain tracts (corpus callosum, internal capsule, external capsule, anterior commissure) resulted in the appearance of numerous CCK immunoreactive fibers not normally seen in the undamaged tracts. Although the possibility remains that cortical CCK neurons may be refractory to transport of retrograde tracers, these results suggest that CCK-like immunoreactive neurons of the rat cerebral cortex are predominantly local circuit neurons and that only minor cortico-cortical and cortico-subcortical CCK-containing projections exist.

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Dynorphin-containing pathways in the substantia nigra and ventral tegmentum: a double labeling study using combined immunofluorescence and retrograde tracing.

A rich plexus of dynorphin (DYN)-containing fibers and terminals is present throughout the substantia nigra-ventral tegmental area (SN-VTA). Lesion studies have indicated that these terminals originate, in part, from DYN-containing cell bodies in the caudate-putamen. We have utilized combined immunofluorescence and retrograde tracing techniques to confirm this finding and to demonstrate the presence of other potential DYN pathways in the region of SN-VTA. The location of DYN-containing cell bodies and fibers was determined by immunohistochemistry in untreated and colchicine-treated adult albino rats. In further double-labeling experiments, animals received injections of fluorescent retrograde tracers into SN-VTA, brainstem or amygdala, followed one to fourteen days later by colchicine treatment. Brains were subsequently processed for combined FITC immunofluorescence and fluorescent dye localization. These experiments provided neuroanatomical evidence for heterogeneous DYN-containing pathways in the SN-VTA. Topographically organized afferents arose from the caudate putamen, amygdala and hypothalamus, while efferents arose from only the most lateral sectors of the SN to the amygdala. While most of the observed descending projections terminated in the SN-VTA, hypothalamic and amygdala projections also continued en passage to the brainstem. These findings implicate DYN systems in striatal and limbic, as well as neuroendocrine, functions.

Amygdala↗

Neurons in the ventral tegmentum have separate populations projecting to telencephalon and inferior olive, are histochemically different, and may receive direct visual input.

The connections of the ventral tegmental area (VTA) and medial terminal nucleus (MTN) of the accessory optic system were studied in the albino rat. Using injection of two fluorescent retrograde tracers it was found that individual neurons of the VTA project to frontal cortices or the inferior olive but not both structures. Using combined retrograde fluorescent tracers and glyoxylic acid histochemistry, it was found that although a third of the cells projecting to frontal cortex contained catecholamine, none of the cells projecting to the inferior olive contained catecholamine. Thus, these portions of the ascending and descending VTA systems are independent. In addition, using injections of the anterograde transneuronal tracer [3H]adenosine into one eye, it was found that cells in the VTA, as well as the MTN, contained the tracer. Therefore, there is a basis for direct retino-mesentelencephalic pathways through the VTA.

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Epidermal growth factor immunoreactive material in the central nervous system: location and development.

Epidermal growth factor (EGF) is a potent mitogen with hormonal activity in the gastrointestinal tract. Material cross-reacting with EGF was detected in the central nervous system of the developing and adult albino rat by the indirect immunofluorescence technique. High concentrations of EGF-cross-reacting material were identified in forebrain and midbrain structures of pallidal areas of the brain. These include the globus pallidus, ventral pallidum, entopeduncular nucleus, substantia nigra pars reticulata, and the islands of Calleja . Thus, EGF may represent another gut-brain peptide with potential neurotransmitter-neuromodulator functions in pallidal structures of the extrapyramidal motor systems of the brain.

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Visual and auditory pathways contain cholecystokinin: evidence from immunofluorescence and retrograde tracing.

The distribution of cholecystokinin (CCK) in the visual and auditory systems of the rat was studied with combined immunofluorescence and fluorescence retrograde tracing techniques. Double-labeled projection neurons in the pathway from the dorsal lateral geniculate nucleus to area 17 of visual cortex, and from the superior olive to the inferior colliculus demonstrated the presence of CCK-containing pathways in the ascending visual and auditory systems. Thus, CCK can be viewed as a neurotransmitter/neuromodulator candidate in ascending sensory systems.

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Substantia nigra and ventral tegmental area projections to cortex: topography and collateralization.

The substantia nigra and ventral tegmental area of the rat were examined by retrograde transport methods to determine the topography and collateralization patterns of projections to cortex and certain subcortical sites. The topographical relationships between cells and their terminal fields were confirmed and clarified by the horseradish peroxidase retrograde transport technique. The collateralization of axons was analyzed by the use of multiple fluorescent tracers. These experiments indicated that individual ventral tegmental area cells do not collateralize extensively to either subcortical or cortical terminal fields. Substantia nigra cells, however, give rise to more highly collateralized axons and single cells may simultaneously innervate different regions of cortex as well as subcortical sites. Substantia nigra cells can be divided with respect to their cortical collateralization patterns into three groups: (1) those that innervate cingulate cortices, (2) those that project to prefrontal and suprarhinal cortices, and (3) those that innervate entorhinal cortex.

Afferent Pathways↗

The crossed mesostriatal projection: neurochemistry and developmental response to lesion.

The projections of substantia nigra and ventral tegmental area (SN-VTA) neurons to either the ipsilateral or contralateral caudate-putamen (CP) were studied in intact and 6-hydroxydopamine-treated rats, using both retrograde transport of fluorescent dyes and measurements of dopamine concentration. After unilateral CP injections of nuclear yellow or granular blue in intact 6- or 30-day-old rats, approximately 1% of the retrogradely labeled cells were located in the contralateral SN-VTA. In 6- or 30-day-old rats which had been injected with 6-hydroxydopamine in the left lateral hypothalamic area (LHA) at 1 day of age, the extent of cell labeling of both the uncrossed projection in the right hemisphere and the crossed projection originating in the left SN-VTA was normal. However, the number of labeled cells of the uncrossed pathway of the left side and the crossed pathway originating in the right SN-VTA were markedly decreased by the lesion, indicating that the crossed nigrostriatal cells decussate before they reach the LHA. The 6-hydroxydopamine-induced decreases in SN-VTA labeling of both the crossed and uncrossed pathway closely matched the degree of dopamine depletion in the lesioned CP at 6 days of age and at 30 days of age. A partial recovery of both measures occurred between days 6 and 30. Thus, retrograde labeling of SN-VTA cells and at 30 days of age. A partial recovery of both measures occurred between days 6 and 30. Thus, retrograde labeling of SN-VTA cells with fluorescent dyes provided a quantitative measure of the dopaminergic innervation of the neostriatum in both the uncrossed and crossed pathways.(ABSTRACT TRUNCATED AT 250 WORDS)

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Dopamine- and cholecystokinin-containing neurons of the crossed mesostriatal projection.

The projection of the substantia nigra-ventral tegmental area (SN-VTA) to the ipsilateral and contralateral caudate-putamen was studied with double-labeling fluorescence techniques in the albino rat. By combining glyoxylic acid histofluorescence with retrograde fluorescence tracers, we were able to determine that 93% of the minor (1-2%) contralateral mesostriatal pathway is catecholaminergic. In addition, combined immunofluorescence and retrograde fluorescence tracer studies showed that 50% of the crossed mesostriatal pathway also arises from cholecystokinin-containing neurons. These results provide evidence for crossed catecholamine- and peptide-containing pathways in the mesostriatal system which is part of the 'prefrontal system' that links the prefrontal cortex through the caudate-putamen, with the thalamus and tectum of each hemisphere.

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The islands of Calleja complex of rat basal forebrain. III. Histochemical evidence for a striatopallidal system.

The characteristics of the islands of Calleja complex (ICC) in the basal forebrain of the rat were studied with immunohistochemistry, histofluorescence, acetylcholinesterase staining, India ink vascular perfusions, electron microscopy, and steroid autoradiography. The ICC contains clusters of granule cells and associated medium-sized and large cells in the surrounding neuropil of the olfactory tubercle and septum-nucleus accumbens interface. The ICCs were found to contain monoamine fibers (dopamine and norepinephrine), neuroactive peptide fibers (leu-enkephalin, met-enkephalin, substance P, cholecystokinin, luteinizing hormone-releasing hormone), acetylcholinesterase-containing somata and dendrites, and medium-sized and large cells that concentrate [3H] estradiol. The specific overlap and combination of putative neurotransmitters in separate compartments of the ICC suggest that these structures contain striatum- and pallidumlike components. Striatumlike regions are defined as the zone in the rim regions of the ICC and are innervated predominantly by dopamine and cholecystokinin inputs. Pallidumlike regions are defined as the synaptic zone near the medium-sized and large cells of the cap and core regions of the ICC and they are innervated predominantly by enkephalin, substance P, and gamma aminobutyric acid inputs. The morphology, connections, and neurotransmitter relationships of the ICC, therefore, resemble classical striatopallidal systems. The additional presence of substances involved in the reproductive neuroendocrine systems (luteinizing hormone-releasing hormone, estradiol-binding cells, especially in the medial ICC, suggest that some ICC are involved in an endocrine corticostriatopallidal system. These endocrine systems resemble other neocortically and allocortically originating corticostriatopallidal systems in terms of their cell types, connections, and neurotransmitter systems. A functional role for the ICC in extrapyramidal motor systems is proposed.

Acetylcholinesterase↗

The origin of cholecystokinin terminals in the basal forebrain of the rat: evidence from immunofluorescence and retrograde tracing.

The origins of cholecystokinin (CCK) fibers in the olfactory tubercle, nucleus accumbens and amygdala of the basal forebrain of the albino rat were studied with combined immunofluorescence and fluorescent retrograde tracing techniques. In each case, the majority of the CCK innervation arises topographically from subpopulations of neurons in the substantia nigra-ventral tegmental area of the midbrain. This ascending CCK input to the forebrain appears to exceed the amount of descending CCK input from the cortex. In this regard, the CCK innervation of limbic structures is quite different from that of the neostriatum. It has been reported that the CCK innervation of the neostriatum is derived primarily from piriform cortex as a descending corticostriatal projection. Limbic structures, on the other hand, are primarily innervated by ascending CCK, as well as local circuit, projections.

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Dopaminergic and non-dopaminergic projections to amygdala from substantia nigra and ventral tegmental area.

The projections from the substantia nigra (SN) and ventral tegmental area (VTA) to the amygdala of the rat were examined by simultaneous visualization of catecholamine (CA) histofluorescence and retrograde tracer. CA-containing cells in lateral VTA, medial SN and the dorsal edge of SN pars compacta were labeled by injections of propidium iodide (PI) into the amygdala. While CA-containing cells were present in SN pars lateralis (SNl), those cells which were labeled by injections into the amygdala did not contain CA. There is, thus, a significant non-DA projection from SNl to the amygdala.

Amygdala↗

The islands of Calleja complex of rat basal forebrain II: connections of medium and large sized cells.

The connections of the medium (10-20 microns) and large (20-35 microns) cells of the islands of Calleja Complex (ICC) were studied in the albino rat with anterograde and retrograde transport of horseradish peroxidase (HRP) and fluorescent tracers. The medium and large size cells were found to project to the ipsilateral olfactory tubercle, ventral pallidum, septum, piriform cortex, periamygdaloid cortex, cortical nuclei of the amygdala, ventral endopiriform nucleus, lateral hypothalamic area, Forel's field H, ventral tegmental area, supramammillary complex, and nuclei gemini of the hypothalamus, midline, intralaminar and medial thalamic nuclei, and lateral habenula. Afferents of the ICC appear to include the same nuclei with the exception of the lateral habenula. In addition, the dorsal raphe projects to the ICC. These connections are consistent with the concept that the ICC is a striato-pallidal structure.

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Mesostriatal projections from ventral tegmentum and dorsal raphe: cells project ipsilaterally or contralaterally but not bilaterally.

The cells of origin of the brainstem projection to the caudate-putamen (CP) were examined in the albino rat by the use of two fluorescent retrograde tracers. Nuclear yellow was injected into the CP of one hemisphere and granular blue was injected into the contralateral CP. Retrogradely labeled cells were studied in the substantia nigra (SN), ventral tegmental area (VTA) and dorsal raphe (DR). The results confirm previous findings indicating the existence of contralateral projections from SN and VTA to the CP. Cells on both sides of the midline of the DR also project to either CP. Contralaterally projecting SN/VTA cells were located in areas of these nuclei which corresponded to the center of the ipsilaterally projecting cell region; the exact locations depended on the placement of the injection in the CP. In DR, contralaterally projecting cells were most often observed near the midline, although labeled cells were occasionally observed in the lateral wings of the DR. Cells labeled by contralateral injections were interdigitated with, but not identical to, cells labelled by ipsilateral injections. That is, contralaterally projecting cells and ipsilaterally projecting cells constituted separate populations within the SN, VTA and DR.

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