Morphometric analysis of ventral mesencephalic neurons retrogradely labeled with Fluoro-Gold following injections in the shell, core and rostral pole of the rat nucleus accumbens

doi:10.1016/0006-8993(95)00556-6

Brain Research

Volume 689, Issue 1, 14 August 1995, Pages 151-156

https://doi.org/10.1016/0006-8993(95)00556-6 Get rights and content

Abstract

Morphologically distinct subsets of mesotelencephalic neurons were sought following retrograde transport of Fluoro-Gold from iontophoretic injections relatively restricted to the medial shell, core or rostral pole subterritories of the nucleus accumbens. The diameters and lengths of Fluoro-Gold immunolabeled dendrites of medial shell-projecting neurons were less than those of core and rostral pole-projecting neurons.

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An update on the connections of the ventral mesencephalic dopaminergic complex
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Citation Excerpt :
A variety of morphological, electrophysiological and molecular biological characteristics of VTA DA neurons vary with their projection targets. Earlier studies showed that DA neurons in the medial part of the VTA projecting to medial Acb are smaller and have fewer and shorter dendritic branches as compared to lateral VTA neurons projecting to more lateral parts of the Acb (Tan et al., 1995). Lammel et al. (2008) extended these findings in a recent study that employed experimental neuroanatomical, electrophysiological, immunohistochemical and laser-dissection techniques to demonstrate one group of neurons centered in the medial VTA that projects to the mPfC, Acb medial shell and core, and basolateral amygdala and another positioned mainly in the lateral VTA that projects to the Acb lateral shell and ventrolateral CPu.
This review covers the intrinsic organization and afferent and efferent connections of the midbrain dopaminergic complex, comprising the substantia nigra, ventral tegmental area and retrorubral field, which house, respectively, the A9, A10 and A8 groups of nigrostriatal, mesolimbic and mesocortical dopaminergic neurons. In addition, A10dc (dorsal, caudal) and A10rv (rostroventral) extensions into, respectively, the ventrolateral periaqueductal gray and supramammillary nucleus are discussed. Associated intrinsic and extrinsic connections of the midbrain dopaminergic complex that utilize gamma-aminobutyric acid (GABA), glutamate and neuropeptides and various co-expressed combinations of these compounds are considered in conjunction with the dopamine-containing systems. A framework is provided for understanding the organization of massive afferent systems descending and ascending to the midbrain dopaminergic complex from the telencephalon and brainstem, respectively. Within the context of this framework, the basal ganglia direct and indirect output pathways are treated in some detail. Findings from rodent brain are briefly compared with those from primates, including humans. Recent literature is emphasized, including traditional experimental neuroanatomical and modern gene transfer and optogenetic studies. An attempt was made to provide sufficient background and cite a representative sampling of earlier primary papers and reviews so that people new to the field may find this to be a relatively comprehensive treatment of the subject.
Vulnerabilities of ventral mesencephalic neurons projecting to the nucleus accumbens following infusions of 6-hydroxydopamine into the medial forebrain bundle in the rat
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Approximately spherical FG injection sites with diameters between 650 and 1000 μm resulted from the injection parameters utilized (Figs. 1B and 2B, D, F and H). The injections were quite similar to those generated in previous studies from this lab [2,43,45]. Only cases with injections that were localized predominantly, if not quite exclusively, in the medial half of the shell (Figs. 1A and 2B and D) or the core (Fig. 2F and H) were evaluated further.
The terminal arbors of dopaminergic projections in the nucleus accumbens (Acb) core degenerate more rapidly, completely and permanently in a variety of neurotoxic circumstances than do those in the medial shell. It is unknown if this always reflects purely losses of the distal parts of axons from the core (as proposed in methamphetamine intoxication), or whether, in some circumstances, the disproportionate loss of core axons may also stem from an intrinsic vulnerability to degeneration of core-projecting neuronal perikarya. Experiments described here addressed this issue in the following manner. Three days after Fluoro-Gold (FG), a retrogradely transported tracer, had been iontophoresed selectively into the core or medial shell of male Sprague–Dawley rats, each received an infusion of saline vehicle containing or lacking 6-hydroxydopamine (6-OHDA) in the ipsilateral medial forebrain bundle (MFB). Twenty-one days later the brains were processed to exhibit ventral mesencephalic neurons containing FG. Application of an unbiased sampling method revealed substantially greater losses of FG labeled neurons relative to controls in rats that had received 6-OHDA lesions and deposition of FG in the Acb core as compared to the medial shell. Of the few core-projecting neurons that remained in the ventral mesencephalon after these lesions, 54% did not co-localize tyrosine hydroxylase immunoreactivity (TH-ir) and, thus, were not expected to degenerate. The capacity to selectively remove core-projecting dopaminergic neurons may be useful in the determination of molecular correlates of vulnerability and resistance to neurotoxicity and to possibly test the role of the core in reinforcement paradigms.
Autoregulation of dopamine synthesis in subregions of the rat nucleus accumbens
2001, European Journal of Pharmacology
The discovery of a core–shell dichotomy within the nucleus accumbens has opened new lines of investigation into the neuronal basis of psychiatric disorders and drug dependence. In the present study, the autoregulation of dopamine synthesis in subdivisions of the rat nucleus accumbens was examined. We measured the accumulation of l-3,4-dihydroxyphenylalanine (DOPA) after the inhibition of aromatic l-amino acid decarboxylase with 3-hydroxylbenzylhydrazine (NSD-1015, 100 mg kg⁻¹) as an in vivo index of dopamine synthesis. The effect of the dopamine D₁/D₂ receptor agonist apomorphine (0, 20, 100, 500 μg kg⁻¹) and the dopamine D₂/D₃ receptor agonist quinpirole (0, 20, 100, 500 μg kg⁻¹) on dopamine synthesis was determined in the dorsolateral core, ventromedial shell, and rostral pole of the nucleus accumbens. DOPA accumulation was also measured in the frontal cortex, olfactory tubercle, and caudate nucleus of the same rats for comparative purposes. The results show that the three sectors of the nucleus accumbens had similar basal levels of DOPA. Both apomorphine and quinpirole produced a decrease in the dopamine synthesis rate in all brain regions examined. In general, the dopamine D₂/D₃ receptor agonist quinpirole produced a significantly greater decrease in DOPA accumulation than the dopamine D₁/D₂ receptor agonist apomorphine. Within the nucleus accumbens, we found no core–shell differences in the agonist-induced suppression of dopamine synthesis, but the rostral pole was less sensitive to the highest dose of both dopamine agonists. These results suggest that differences in dopamine function between the core and shell might not involve region-specific differences in the receptor-mediated autoregulation of dopamine neurotransmission. Moreover, the blunted effect of dopamine agonists in the rostral pole illustrates that this region of the accumbens is functionally distinct, possibly due to a lower dopamine receptor reserve when compared to the core and shell.
Catecholamine systems in the brain of vertebrates: New perspectives through a comparative approach
2000, Brain Research Reviews
Citation Excerpt :
In turtles, PNMTi cell bodies lie in locations that correspond to those found for the C1 and C2 adrenergic cell groups of mammals, but, in a gekkonid lizard, only a C1 group is recognized [656,661]. Because of their involvement in neurological diseases such as Parkinson’s disease, the organization and connections of the mammalian midbrain A8–A10 CA cell groups, and particularly their mesostriatal projections, have been extensively studied [230,331,411,412,569,570,711]. Although the DA cells of the A8–A10 groups form a continuum without clear boundaries between groups, experimental hodological studies have shown that the ascending midbrain projections are topographically organized.
A comparative analysis of catecholaminergic systems in the brain and spinal cord of vertebrates forces to reconsider several aspects of the organization of catecholamine systems. Evidence has been provided for the existence of extensive, putatively catecholaminergic cell groups in the spinal cord, the pretectum, the habenular region, and cortical and subcortical telencephalic areas. Moreover, putatively dopamine- and noradrenaline-accumulating cells have been demonstrated in the hypothalamic periventricular organ of almost every non-mammalian vertebrate studied. In contrast with the classical idea that the evolution of catecholamine systems is marked by an increase in complexity going from anamniotes to amniotes, it is now evident that the brains of anamniotes contain catecholaminergic cell groups, of which the counterparts in amniotes have lost the capacity to produce catecholamines. Moreover, a segmental approach in studying the organization of catecholaminergic systems is advocated. Such an approach has recently led to the conclusion that the chemoarchitecture and connections of the basal ganglia of anamniote and amniote tetrapods are largely comparable. This review has also brought together data about the distribution of receptors and catecholaminergic fibers as well as data about developmental aspects. From these data it has become clear that there is a good match between catecholaminergic fibers and receptors, but, at many places, volume transmission seems to play an important role. Finally, although the available data are still limited, striking differences are observed in the spatiotemporal sequence of appearance of catecholaminergic cell groups, in particular those in the retina and olfactory bulb.
On the altered expression of tyrosine hydroxylase and calbindin-D 28kD immunoreactivities and viability of neurons in the ventral tegmental area of Tsai following injections of 6-hydroxydopamine in the medial forebrain bundle in the rat
2000, Brain Research
Citation Excerpt :
This suggests, but does not prove, that VTA neurons that give rise to the core innervation, of which many express CB-ir [37], were preferentially caused to degenerate by the lesions. The actual relative losses of accumbens core vs. shell CB-ir neuron profiles remain to be addressed empirically by labeling ventral mesencephalic neurons with a retrogradely transported marker following placement in the core and shell of the nucleus accumbens [2,36,37] in rats that also get injections of 6-OHDA into the medial forebrain bundle. Nevertheless, it is conditionally concluded that CB-ir is expressed by a subset of TH-ir VTA neurons that is at least as vulnerable to 6-OHDA as TH-ir neurons lacking CB.
Calbindin-D 28kD is a calcium binding protein reported to protect neurons from degeneration by buffering intracellular calcium. It is expressed in midbrain dopaminergic neurons reported to be relatively resistant to degeneration in Parkinson’s disease and certain of its animal models. Lesions of the nigrostriatal pathway produced in rats following injection of 6-hydroxydopamine result in a neurochemical profile similar to that seen in patients with Parkinson’s disease. In the present study, brains were processed to exhibit tyrosine hydroxylase- and calbindin-D 28kD immunoreactivities in sections through the ventral mesencephalon at 3, 7, 10, 14 and 21 days after 6-hydroxydopamine had been injected into the medial forebrain bundle. Numbers of ventral mesencephalic calbindin-D 28kD immunoreactive neurons were significantly reduced ipsilateral to the lesions at 3 days post-lesion and, following slight recovery, remained significantly depleted through post-lesion day 21. The densities of calbindin-D 28kD and tyrosine hydroxylase immunoreactive neurons were different only at the 3 day post-lesion time point, when the apparent loss of calbindin-D 28 kD immunoreactive profiles was significantly greater. A lesion-induced increase in the proportion of neurons exhibiting both calbindin-D 28kD and tyrosine hydroxylase immunoreactivities, expected if calbindin-D 28kD is neuroprotective, was observed in the substantia nigra, pars compacta, but not in the ventral tegmental area. It is concluded that, while the observed losses of tyrosine hydroxylase and calbindin-D 28kD immunoreactivities do not necessarily reflect neuronal degeneration, they are not consistent with CB confering a neuroprotective advantage in the ventral tegmental area following 6-OHDA lesions as administered in this study.
Comparative effects of neurotensin, neurotensin(8-13) and [D- Tyr<sup>11</sup>]neurotensin applied into the ventral tegmental area on extracellular dopamine in the rat prefrontal cortex and nucleus accumbens
2000, Neuroscience
Ejections of 10⁻⁵–10⁻³ M neurotensin into the ventral tegmental area increased dopamine efflux measured by electrochemical approaches in the prefrontal cortex of anaesthetized rats. In the same conditions, the effects evoked on dopamine efflux by 10⁻⁵ M neurotensin(8-13) and [D-Tyr¹¹]neurotensin were different from each other and depended on the explored area: the prefrontal cortex and the caudal and rostral nucleus accumbens. In the prefrontal cortex, neurotensin(8-13) was as potent as neurotensin, whereas [D-Tyr¹¹]neurotensin was ineffective. In the caudal nucleus accumbens, when considering the initial intensity of the effect, neurotensin(8-13) and neurotensin appeared more potent than [D-Tyr¹¹]neurotensin. In contrast, in the rostral nucleus accumbens, neurotensin(8-13) was less potent than [D-Tyr¹¹]neurotensin and neurotensin.
These results support the differential involvement of two pharmacologically distinct neurotensin receptor entities on ventral tegmental area neurons in the modulation of mesolimbic and mesocortical dopaminergic activity.

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Morphometric analysis of ventral mesencephalic neurons retrogradely labeled with Fluoro-Gold following injections in the shell, core and rostral pole of the rat nucleus accumbens

Abstract

Brain Res.

Neurosci. Lett.

Mol. Brain Res.

Brain Res.

Neurosci. Lett.

J. Neurosci. Methods

Brain Res.

Neuroscience

Ascending monoamine neurons to the telencephalon and diencephalon

Acta Physiol. Scand.

A quantitative study on the nigro-neostriatal dopamine neuron system in the rat

Acta Physiol. Scand.

The patterns of afferent innervation of the core and shell in the ‘accumbens’ part of the rat ventral striatum: immunohistochemical detection of retrogradely transported Fluoro-Gold

J. Comp. Neurol.

The current status of the dopamine hypothesis of schizophrenia

Neuropsychopharmacology

Pharmacological characterization of dopamine systems in the nucleus accumbens core and shell

Neuroscience

Verteilung von Noradrenalin und Dopamin (3-Hydroxytryramin) im Gehirn des Menschen un ihr Verhalten Bein Erkrankungen des extrapyramidalen Systems

Wien Klin. Wochenshcr.

Substantia nigra