The ventral striatum, which prominently includes the nucleus accumbens (Acb), is a heterogeneous area. Within the Acb of rats, a peripherally located shell and a centrally situated core can be recognized that have different connectional, neurochemical, and functional identities. Although the Acb core resembles in many respects the dorsally adjacent caudate-putamen complex in its striatal character, the Acb shell has, in addition to striatal features, a more diverse array of neurochemical characteristics, and afferent and efferent connections. Inputs and outputs of the Acb, in particular of the shell, are inhomogeneously distributed, resulting in a mosaical arrangement of concentrations of afferent fibers and terminals and clusters of output neurons. To determine the precise relationships between the distributional patterns of various afferents (e.g., from the prefrontal cortex, the basal amygdaloid complex, the hippocampal formation, and the midline/intralaminar thalamic nuclei) and efferents to the ventral pallidum and mesencephalon, neuroanatomical anterograde and retrograde tracing experiments were carried out. The results of the double anterograde, double retrograde, and anterograde/retrograde tracing experiments indicate that various parts of the shell (dorsomedial, ventromedial, ventral, and lateral) and the core (medial and lateral) have different input-output characteristics. Furthermore, within these Acb regions, various populations of neurons can be identified, arranged in a cluster-like fashion, onto which specific sets of afferents converge and that project to particular output stations, distinct from the input-output relationships of neighboring, cluster-like neuronal populations. These results support the idea that the nucleus accumbens may consist of a collection of neuronal ensembles with different input-output relationships and, presumably, different functional characteristics.
The pre- and postnatal development of the dopaminergic innervation in the prefrontal cortex (PFC) of the rat is described from embryonic day 14 through postnatal day 90. By embryonic day 15 the dopamine (DA)-containing fibers reach the anlage of the lateral neocortex; 2 days later the first fibers have reached the subplate of the future prefrontal cortex. The process of entering the cortical plate starts just before birth. Prenatally, some dopaminergic fibers can be observed in the marginal zone of both the lateral and the medial wall of the hemisphere. Within 48 hours after birth a large number of dopaminergic fibers can be observed in the marginal zone, i.e., the future layer I, in some subareas of the PFC. A transient appearance of DA-positive fibers is noticed in the late embryonic and early postnatal periods especially in the marginal zone and possibly in the superficial layers of the pregenual cingulate cortex. Changes in the morphology of DA fibers at P4 suggest that the actual DA innervation starts at this age. From postnatal day 6 the different subareas of the PFC can be recognized according to the characteristics of the topographical distribution of the dopaminergic fibers. Until postnatal day 60 the density of the dopaminergic fibers continues to increase. No difference in density and topography was observed between postnatal days 60 and 90.
We found that magnocellular oxytocin neurons in adult female rats exhibit an endogenous GABA(A) receptor subunit switch around parturition: a decrease in alpha1:alpha2 subunit mRNA ratio correlated with a decrease in allopregnanolone potentiation and increase in decay time constant of the GABA(A) receptor-mediated IPSCs in these cells. The causal relationship between changes in alpha1:alpha2 mRNA ratio and the ion channel kinetics was confirmed using in vitro antisense deletion. Further, GABA(A) receptors exhibited a tonic inhibitory influence upon oxytocin release in vivo, and allopregnanolone helped to restrain oxytocin neuron in vitro firing only before parturition, when the alpha1:alpha2 subunit mRNA ratio was still high. Such observations provide evidence for the physiological significance of GABA(A) receptor subunit heterogeneity and plasticity in the adult brain.
In the caudate-putamen of the rat a patch/matrix organization can be recognized on the basis of the immunohistochemical distribution of several markers, which include enkephalin, substance P, dopamine, and calcium-binding protein. In the present experiments the distributional relations of these markers were investigated in the nucleus accumbens. The distribution of enkephalin fibers shows different inhomogeneities according to their location in the nucleus. Rostrally, heavily labeled areas stand out against a moderately stained background, whereas caudally, in medial and ventral parts of the nucleus, lightly stained areas delineate regions in the moderately stained neuropil. In the distribution of substance P, areas with high staining intensity were observed in the medial and ventral parts of the nucleus accumbens. Inhomogeneities in the distribution of strong dopamine immunoreactivity consist of weakly immunoreactive areas throughout the rostrocaudal extent of the nucleus accumbens and extremely heavily labeled areas in the medial and ventral parts of the nucleus. Calcium-binding protein immunoreactivity can only be detected in dorsal parts of the nucleus. The generally intense immunostaining for calcium-binding protein is interspersed with "blanks" of weak immunoreactivity. The heavily and moderately labeled enkephalin areas each maintain specific relations with inhomogeneities in the distribution of substance P, dopamine, and calcium-binding protein. Rostrally, the heavily labeled enkephalin areas coincide with areas strongly immunostained for calcium-binding protein and with lightly stained areas in the dopamine and substance P immunoreactivity patterns. In the same region lightly stained areas in the enkephalin distribution match heavily labeled substance P areas. Caudally, in the border region of the nucleus accumbens and the caudate-putamen, the heavily labeled enkephalin areas are either related to "blanks" or to the intense staining regions in the calcium-binding protein immunoreactivity distribution. The moderately labeled enkephalin areas caudomedially in the nucleus accumbens are in register with the heavily labeled regions in the distribution of substance P and with the extremely heavily labeled regions in the distribution of dopamine. Relations with connectivity are discussed and the inhomogeneities are compared to those in the caudate-putamen. It is concluded that in the ventral striatum either one patch and one matrix compartment exist with different immunohistochemical relationships or there are several compartments with different immunohistochemical characteristics and different input-output relations.
The nucleus accumbens in the rat has been parcelled into shell and core subdivisions. Despite accumulating evidence for such a division of the nucleus accumbens, these territories have not been delineated throughout the rostrocaudal extent of the nucleus. In the present study, an attempt has been made to delineate the shell and core using the distribution of calcium-binding protein immunoreactivity, substance P immunoreactivity and acetylcholinesterase activity in transverse and horizontal sections through the nucleus accumbens. It was found that the pattern of calcium-binding protein immunoreactivity provides the most unequivocal criterion to divide the nucleus accumbens into a ventral and medial, peripheral shell displaying low to moderate immunostaining, and a more laterally and dorsally located, strongly stained inner core. In most parts of the nucleus, borders seen in the calcium-binding protein immunoreactivity pattern can also be recognized in the distributions of substance P immunoreactivity and acetylcholinesterase activity. It is concluded that the shell occupies most of the rostral part of the nucleus accumbens, whereas rostrally the core is represented only in the most lateral part. Differences in staining intensities for all three markers indicate that both the shell and core have a heterogeneous structure. Patterns of connectivity appear to support the division of the nucleus accumbens as indicated by calcium-binding protein immunoreactivity in the present study.
Dopamine (DA) in the dorsal and ventral striatum is associated with different aspects of locomotor activity control. The ventral striatum may form an interface between the limbic system and the extrapyramidal motor system. The distribution of dopaminergic fibers in this interface position was studied in detail with a method applying antibodies against DA. Furthermore, the ultrastructural morphology of the DA fibers was examined by means of immuno-electron microscopy. The results show that DA immunoreactivity is distributed over the ventral striatum in a highly compartmentalized fashion. In the dorsal striatum few compartments were found. The DA fibers in the ventral striatum establish mainly symmetric synaptic contacts, preferably with dendritic shafts and spines. The results are discussed in relation to previous data concerning the light and electron-microscopic identification of catecholaminergic fibers in the ventral and dorsal striatum.
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