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G F Alheid

Publications and source records attributed to G F Alheid.

34 records · Page 2Linked to original sources

The ventral striatopallidothalamic projection: II. The ventral pallidothalamic link.

The projection of ventral pallidal neurons to the mediodorsal nucleus of the thalamus (MD) was examined in rats by combined retrograde transport of horseradish peroxidase (HRP) after injections in the MD and glutamate decarboxylase (GAD) immunocytochemistry at light and electron microscopic levels, with and without prior exposure of the brains to colchicine. HRP was transported to the soma of medium-sized and large ventral pallidum neurons, which along with their long, large dendrites were contacted by many glutamate decarboxylase immunoreactive synaptic boutons. The retrograde tracer positive neurons bore a remarkable resemblance to the projecting cells of the globus pallidus and entopeduncular nucleus. When colchine exposure was included in the tissue preparation, some but not all tracer positive cells also exhibited cytoplasmic GAD immunoreactivity.

Animals↗

Mapping of transmitter-specific connections: simultaneous demonstration of anterograde degeneration and changes in the immunostaining pattern induced by lesions.

This paper describes simple procedures which allow immunohistochemistry to be combined with a newly developed silver degeneration technique for the purpose of mapping transmitter-specific connections on the light microscopic level. Conditions of fixation, survival time and immunohistochemistry that contribute to optimal results are discussed.

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Cholecystokinin innervation of the ventral striatum: a morphological and radioimmunological study.

Immunocytochemistry, radioimmunological assay after surgical cuts, anterograde degeneration and retrograde tracing of fluorescent dyes were used in order to elucidate the cholecystokinin-containing afferents to the ventral striatum (nucleus accumbens, olfactory tubercle and ventral part of the caudate-putamen). In agreement with the report by Hökfelt et al., midbrain cholecystokinin-containing cells supply the posteromedial parts of the nucleus accumbens and olfactory tubercle, as well as the subcommissural part of caudate-putamen. Brainstem cholecystokinin afferents also reach more rostral parts of the ventral striatum including the rostrolateral olfactory tubercle. The ascending cholecystokinin axons enter the medial forebrain bundle at the meso-diencephalic border and maintain a rough medial to lateral topography at the caudal diencephalon. A second major cholecystokinin pathway, with possible origin in the piriform and medial prefrontal cortices and/or the amygdala, projects to the subcommissural caudate-putamen, the olfactory tubercle, the lateral part of the nucleus accumbens and the dorsal part of the bed nucleus of stria terminalis. Finally, the rostral part of the dorsal caudate-putamen receives a substantial cholecystokinin innervation from the basolateral amygdala and possibly from the neocortex. According to radioimmunological data, the descending telencephalic cholecystokinin system accounts for about 60% of all cholecystokinin in the rostral forebrain. The combined use of morphological and biochemical methods provided evidence for a partially overlapping distribution and possible interaction between an ascending brainstem and descending telencephalic cholecystokinin fiber systems within the striatum and related rostral forebrain areas.

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Quantitative determination of collateral anterior olfactory nucleus projections using a fluorescent tracer with an algebraic solution to the problem of double retrograde labeling.

The bilateral projections of the rat anterior olfactory nucleus (AON) were evaluated using retrograde fluorescent tracers. Competitive effects of these tracers led to severe underestimation of bilaterally projecting neurons, when double-labeled cells were counted. The underestimate was corrected using a numerical approach, which is of general utility for problems in double labeling and requires only a single tracer. With this method we estimated that approximately 63% of AON neurons project bilaterally to the olfactory bulbs, except for the external part which projects exclusively to the contralateral olfactory bulb. No other AON neurons project only to the contralateral bulb.

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An algebraic approach to the detection of multiple markers in complex neuronal systems.

An important class of neuroanatomical problems requires identification of neurons that contain two or more substances. Based on the additivity of neuronal elements that are independently labeled, a simple numerical approach may be applied to these problems. This approach provides a sensitive and viable alternative to direct multiple labeling of endogenous or transported neuronal markers.

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The ventral pallidal projection to the mediodorsal thalamus: a study with fluorescent retrograde tracers and immunohistofluorescence.

We have examined rat basal forebrain projections to the mediodorsal thalamic nucleus (MD) by making injections of retrogradely transported fluorescent tracers into the MD. Additionally, in some animals, we also stained sections for glutamate decarboxylase (GAD) by the indirect fluorescent antibody technique. Our results demonstrate that the following basal forebrain areas project to the MD: lateral orbital cortex, agranular insular cortex superficial to claustrum, primary olfactory cortex, diagonal band nuclei, ventral pallidum, and amygdala. A large number of labeled cells are present in the olfactory tubercle, and these cells are almost without exception located in dense GAD-positive ventral pallidal areas rather than in striatal regions of the tubercle. This ventral pallidal projection to the MD strengthens the concept of a ventral striatal-pallidal system in parallel to the classic striatal-pallidal system which projects to the ventral thalamus. These results are also discussed in relationship to the olfactory system.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗

Deficits in food and water intake after knife cuts that deplete striatal DA or hypothalamic NE in rats.

Knife cuts ventral or medial to the striatum were used to interrupt some of the principal connections of this structure. All of the cuts depleted striatal dopamine and produced aphagia and adipsia but there was no indication that the two classes of effects were always correlated. Cuts medial to the striatum produced the most severe DA depletions, persistent aphagia and adipsia, and the full complement of deficits in responding to glucoprivic and hydrational challenges that characterize rats that have recovered from lateral hypothalamic lesions. Cuts ventral to posterior portions of the striatum produced comparable periods of aphagia and adipsia (but few of the persisting impairments in responsiveness to regulatory challenges) even though their effect on striatal DA was relatively small (the average depletion was 51% compared to 89% for rats with cuts medial to the striatum). A second group of rats with cuts below more anterior aspects of the striatum sustained severe DA depletions (70%) but only very brief periods of aphagia and adipsia and only slight deficits in responding to osmotic challenges. The effects of the DA depleting cuts were compared with the behavioral consequences of coronal cuts in the midbrain tegmentum which selectively depleted hypothalamic norepinephrine. These cuts did not produce reliable effects on either food or water intake but abolished the normal feeding response to 2-deoxy-d-glucose without affecting the response to insulin. A correlational analysis of the biochemical and behavioral results of our cuts indicated a significant positive relationship between drinking in response to cellular thirst stimuli and hypothalamic NE as well as striatal DA. The postoperative body weights of our experimental animals were positively correlated with striatal dopamine and negatively related to hypothalamic norepinephrine.

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A correlational analysis of the effects of surgical transections of three components of the MFB on ingestive behavior and hypothalamic, striatal, and telencephalic amine concentrations.

A retractable wire knife was used to transect medial or lateral components of the MFB or its lateral projections to the striatum and amygdaloid complex. All cuts produced significant depletions of NE, DA, and 5-HT from telencephalon and striatum but little or no effect on hypothalamic NE or 5-HT. Two of our cuts resulted in aphagia and adipsia, the third in hyperphagia and obesity. A detailed correlational analysis of the magnitude and direction of the behavioral and biochemical consequences of our cuts indicated that the ingestive behavior of all of our experimental animals (including animals which had been aphagic and adipsic after surgery as well as animals which were hyperphagic and obese) was positively correlated with the concentration of DA in striatum and telencephalon and negatively correlated with telencephalic 5-HT. Less consistent evidence for facilitatory noradrenergic influences on food intake was also obtained. Our results suggest that the regulation of food intake may be the result of an interaction between telencephalic serotonergic mechanisms and dopaminergic pathways which exert opposite effects on ingestive behavior.

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Supersensitivity to norepinephrine or dopamine antagonists after knife cuts that produce aphagia and adipsia in rats.

Aphagia and adipsia of equivalent duration were produced by knife cuts along the lateral border of the hypothalamus (PH cuts), or the medial surface of the globus pallidus (MP cuts) in male albino rats. Striatal dopamine (DA) was reduced by 75% in animals with PH cuts but only 50% by MP cuts. Hypothalamic norepinephrine was reduced 25% by PH cuts and was unaffected by MP cuts. Aphagia and adipsia were positively correlated with DA depletions only in rats with PH cuts. Presurgical catecholamine depletions produced by chronic injections of alpha-methyl-p-tyrosine did not alter the duration of aphagia or adipsia resulting from these knife cuts. However, following recovery of ingestive behavior, rats with PH and MP cuts were supersensitive to the anorexic effects of the dopamine-beta-hydroxylase inhibitor, diethyldithiocarbamate. Exaggerated anorexia was also observed after DA blockade by haloperidol or alpha-adrenergic blockade by phenoxybenzamine. The most pronounced effects of catecholamine blockade were observed in rats with PH cuts.

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Behavioral and biochemical effects of knife cuts that preferentially interrupt principal afferent and efferent connections of the striatum in the rat.

Knife cuts were made that preferentially interrupted (a) the nigrostriatal pathway; (b) pallidofugal projections to the lower brainstem; (c) caudate-pallidal interconnections; and (d) fibers entering or leaving the striatum ventrally. The effects of these cuts on conditioned (shuttle box) avoidance, passive avoidance, swimming escape, sucrose-rewarded alley running, locomotor activity, and various measures of sensory-motor function were examined. The norepinephrine, dopamine and serotonin content of the striatum, residual forebrain and hypothalamus were determined following the completion of behavioral testing. The pattern of results suggests that striatal functions which are significantly influenced by several afferent and efferent connections are essential for the acquisition and, perhaps, execution of complex behavior in appetitive as well as aversive test paradigms. A special role for the dopaminergic afferents to the striatum was not established in these tests.

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Regulatory deficits after surgical transections of three components of the MFB: correlation with regional amine depletions.

Parasagittal knife cuts along the lateral border of the diencephalon (PS), coronal cuts across the lateral (LMFB) or medial (MMFB) components of the medial forebrain bundle reproduce most of the persisting deficits in responding to glucoprivic and hydrational challenges that characterize rats with lateral hypothalamic lesions or intracranial injections of 6-hydroxydopamine (60HDA). Each of these cuts produced a differnet pattern of regulatory deficits, suggesting that individual components of the LH syndrome may be mediated by different neural substrates. This interpretation is supported by the results of our correlational analysis of the relationships between specific behavioral and biochemical effects of our cuts. For example, feeding responses to insulin were reliably correlated with striatal DA concentrations but feeding responses to 2-deoxy-d-glucose (2DG) were not. Water intake during periods of food deprivation was reliably correlated with striatal DA but water intake after an experimental osmotic challenge was not. Only one of the common persisting deficits (impaired feeding response to peripheral injections of insulin) was positively correlated with the duration of aphagia and adipsia.

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GABA stimulation and blockade in the hypothalamus and midbrain: effects on feeding and locomotor activity.

Microinjections of the gamma-aminobutyric acid (GABA) antagonist, bicuculline methiodide (BM) (100 ng), into the anterolateral hypothalamus (LH) increased ingestion of sweet milk. A subsequent injection of BM 48 hrs. later produced a type of kindling effect consisting of feeding related automatisms, such as gnawing and biting. The behavioral effects of injections of 100 ng of GABA into the LH were variable. GABA injections into the ventromedial hypothalamus (VMH) reliably increased food intake. GABA injections into the origin of the nigrostriatal dopamine (DA) neurons in the substantia nigra (SN) suppressed it. Similar injections into the origin of the mesolimbic DA cells in the ventral tegmental area (VTA) had no effect on feeding behavior. Following BM injections into the SN, a moderate increase in tilt box activity was observed. A second injection of the GABA blocker 6 days later exaggerated this effect. Short latency extreme hyperactivation was accompanied by unidirectional barrel rolling which persisted until blocked by local injections of GABA.

Aminobutyrates↗

Temporal lobe lesion-induced obesity in rats: an anatomical investigation of the posterior amygdala and hippocampal formation.

Bilateral lesions centered in the posterodorsal amygdala of female rats resulted in hyperphagia and excessive weight gain (mean = 65.3 g in 20 days compared to 6.8 g for control animals). The brain damage always extended posteriorly into the ventral hippocampal formation. However, lesions that were confined to the ventral hippocampus or amygdalohippocampal area had no effect on daily food intake or body weight, nor did lesions at any other hippocampal site. In a previous study, lesions of the basolateral, corticomedial, and anterior groups of amygdaloid nuclei failed to affect food intake or body weight. It is concluded that the posterodorsal aspect of the amygdala is the critical site for this experimentally induced obesity syndrome. New coordinates for the effective site are presented.

Amygdala↗

Parvalbumin in respiratory neurons of the ventrolateral medulla of the adult rat.

A column of parvalbumin immunoreactive neurons is closely associated with the location of respiratory neurons in the ventrolateral medulla of the rat. The majority (66%) of bulbospinal neurons in the medullary ventral respiratory column (VRC) that were retrogradely labeled by tracer injections in the phrenic nucleus were also positive for parvalbumin. In contrast, only 18.8% of VRC neurons retrogradely labeled after a tracer injection in the VRC, also expressed parvalbumin. The average cross-sectional area of VRC neurons retrogradely labeled after VRC injections was 193.8 microm2 +/- 6.6 SE. These were significantly smaller than VRC parvalbumin neurons (271.9 microm2 +/- 12.3 SE). Parvalbumin neurons were found in the Bötzinger Complex, the rostral ventral respiratory group (VRG), and the caudal VRG, areas which all contribute to the bulbospinal projection. In contrast, parvalbumin neurons were sparse or absent in the preBötzinger Complex and in the vicinity of the retrotrapezoid nucleus, areas that have few bulbospinal projections. Parvalbumin was rarely colocalized within Neurokinin-1 receptor positive (NK1R) VRC neurons, which are found in the preBötzinger complex and in the anteroventral part of the rostral VRG. Parvalbumin neurons in the Bötzinger Complex and rostral VRG help define the rostrocaudal extent of these regions. The absence of parvalbumin neurons from the intervening preBötzinger complex also helps establish the boundaries of this region. Regional boundaries described in this manner are in good agreement with earlier physiological and anatomical studies. Taken together, the distributions of parvalbumin, NK1R and bulbospinal neurons suggest that the rostral VRG may be subdivided into distinct, anterodorsal, anteroventral, and posterior subdivisions.

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