Henk J. Groenewegen

Putting a spin on the dorsal–ventral divide of the striatum

Since its conception three decades ago, the idea that the striatum consists of a dorsal sensorimotor part and a ventral portion processing limbic information has sparked a quest for functional correlates and anatomical characteristics of the striatal divisions. But this classic dorsal-ventral distinction might not offer the best view of striatal function. Anatomy and neurophysiology show that the two striatal areas have the same basic structure and that sharp boundaries are absent. Behaviorally, a distinction between dorsolateral and ventromedial seems most valid, in accordance with a mediolateral functional zonation imposed on the striatum by its excitatory cortical, thalamic and amygdaloid inputs. Therefore, this review presents a synthesis between the dorsal-ventral distinction and the more mediolateral-oriented functional striatal gradient.

Organization of the projections from the subiculum to the ventral striatum in the rat. A study using anterograde transport of Phaseolus vulgaris leucoagglutinin

The projections of the subiculum, as the main output structure of the hippocampal formation, to the striatum were studied in the rat using the anterograde tracer Phaseolus vulgaris leucoagglutinin. It appears that not only the entire nucleus accumbens, part of the so-called ventral striatum, receives fibres from the subiculum, but that the hippocampal projection area in the striatum includes also the most medial, ventral, rostral and caudal parts of the caudate-putamen complex. Moreover, a relatively small number of fibres and terminals are present in the striatal elements of the medial part of the olfactory tubercle. The projections to the ventral and caudal parts of the caudate-putamen are predominantly derived from the ventral subiculum, whereas the projections to the rostral part of the caudate-putamen are derived from the dorsal subiculum. Furthermore, with respect to the subiculum-accumbens pathway a topographical organization could be established. Thus, the ventral or temporal part of the subiculum projects predominantly to the caudomedial part of the nucleus accumbens, and to a lesser degree to its rostromedial portion, whereas progressively more dorsal or septal parts of the subiculum send fibres to successively more lateral and rostral portions of the nucleus accumbens. Very sparse projections are found to the contralateral nucleus accumbens, arranged in a topographical manner similar to the ipsilateral projections. An important observation with respect to the structure of the nucleus accumbens is that the subicular terminations are inhomogeneously distributed, although a relation with earlier described mosaic patterns in the connectivity and neurochemical composition of the nucleus is not yet clear. Subicular fibres have their densest terminations in relatively cell-poor regions of the nucleus accumbens, and in particular tend to avoid small cell clusters.

The nucleus accumbens as a complex of functionally distinct neuronal ensembles: an integration of behavioural, electrophysiological and anatomical data.

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Organization of the afferent connections of the mediodorsal thalamic nucleus in the rat, related to the mediodorsal-prefrontal topography.

The aim of the present study was to determine the organization of the afferents of the mediodorsal thalamic nucleus in relation to the reciprocal connections of this nucleus with different areas of the prefrontal cortex. For this purpose injections of horseradish peroxidase, or horseradish peroxidase conjugated to wheatgerm agglutinin were placed in different parts of the mediodorsal nucleus. These experiments revealed the organization of the reciprocal mediodorsal-prefrontal connections since wheatgerm agglutinin-horseradish peroxidase is transported effectively in anterograde and retrograde directions. Injections of wheatgerm agglutinin-horseradish peroxidase or fluorescent tracers were placed in different portions of the prefrontal cortex, and the lectin Phaseolus vulgaris leucoagglutinin was injected in the mediodorsal nucleus in order to verify in more detail the point-to-point relationship in the mediodorsal-prefrontal connections. The organization of a number of the subcortical afferents to the mediodorsal nucleus was determined in detail using injections of Phaseolus vulgaris leucoagglutinin, wheatgerm agglutinin-horseradish peroxidase, or tritiated amino acids in areas identified as a source of mediodorsal afferents in the retrograde tracing experiments. These anterograde tracers were injected in different parts of the pallidal complex, the amygdala, the lateral hypothalamus, the lateral entorhinal cortex, the ventral mesencephalon, the superior colliculus and the dorsal tegmental region. The results of the present experiments indicate that the mediodorsal nucleus, on the basis of its cyto-, myelo- and chemoarchitecture as well as the organization of its reciprocal connections with the prefrontal cortex, can be subdivided into a medial, a central, a lateral and a paralamellar segment. Apart from this subdivision along a mediolateral axis, rostrocaudal and dorsoventral differences are also evident in the structural organization and connectivity of the mediodorsal nucleus. A number of subcortical structures send fibres to all parts of the mediodorsal nucleus. The reticular thalamic nucleus projects to the mediodorsal nucleus in a topographical way such that its rostral part is connected with the rostral part of the nucleus, whereas more caudal and ventral areas in the reticular thalamic nucleus are connected with more caudal parts of the mediodorsal nucleus. Regions in the brainstem that project to all parts of the mediodorsal nucleus include the mesencephalic raphé nuclei, the locus coeruleus, the rostral part of the central gray substance and the reticular formation.(ABSTRACT TRUNCATED AT 400 WORDS)

The medial prefrontal cortex in the rat: evidence for a dorso-ventral distinction based upon functional and anatomical characteristics

The prefrontal cortex in rats can be distinguished anatomically from other frontal cortical areas both in terms of cytoarchitectonic characteristics and neural connectivity, and it can be further subdivided into subterritories on the basis of such criteria. Functionally, the prefrontal cortex of rats has been implicated in working memory, attention, response initiation and management of autonomic control and emotion. In humans, dysfunction of prefrontal cortical areas with which the medial prefrontal cortex of the rat is most likely comparable is related to psychopathology including schizophrenia, sociopathy, obsessive-compulsive disorder, depression, and drug abuse. Recent literature points to the relevance of conducting a functional analysis of prefrontal subregions and supports the idea that the area of the medial prefrontal cortex in rats is characterized by its own functional heterogeneity, which may be related to neuroanatomical and neurochemical dissociations. The present review covers recent findings with the intent of correlating these distinct functional differences in the dorso-ventral axis of the rat medial prefrontal cortex with anatomical and neurochemical patterns.

Convergence and Segregation of Ventral Striatal Inputs and Outputs

ABSTRACT: 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.

Chapter 5 The anatomical relationship of the prefrontal cortex with the striatopallidal system, the thalamus and the amygdala: evidence for a parallel organization

Recent findings in primates indicate that the connections of the frontal lobe, the basal ganglia, and the thalamus are organized in a number of parallel, functionally segregated circuits. In the present account, we have focused on the organization of the connections between the prefrontal cortex, the basal ganglia and the mediodorsal thalamic nucleus in the rat. It is concluded that in this species, in analogy with the situation in primates, a number of parallel basal ganglia-thalamocortical circuits exist. Furthermore, data are presented indicating that the projections from particular parts of the amygdala and from individual nuclei of the midline and intralaminar thalamic complex to the prefrontal cortex and the striatum are in register with the arrangements in the parallel circuits. These findings emphasize that the functions of the different subregions of the prefrontal cortex cannot be considered separately but must be viewed as components of the integrative functions of the circuits in which they are involved.

Restricted cortical termination fields of the midline and intralaminar thalamic nuclei in the rat

The projections from the midline and intralaminar thalamic nuclei to the cerebral cortex were studied in the rat by means of anterograde tracing with Phaseolus vulgaris-leucoagglutinin. The midline and intralaminar nuclear complex taken as a whole projects to widespread, predominantly frontal, cortical areas. Each of the constituent thalamic nuclei has a restricted cortical projection field that overlaps only slightly with the projection fields of adjacent midline and intralaminar nuclei. The projections of the intralaminar nuclei cover a larger cortical area than those of the midline nuclei. The laminar distributions of fibres from individual midline and intralaminar thalamic nuclei are different and include both deep and superficial cortical layers. The parataenial, paraventricular and intermediodorsal midline nuclei each project to circumscribed parts of the prefrontal cortex and the hippocampal and parahippocampal regions. In the prefrontal cortex, the projections are restricted to the medial orbital, infralimbic, ventral prelimbic and agranular insular fields, and the rostral part of the ventral anterior cingular cortex. In contrast to the other midline nuclei, the rhomboid nucleus projects to widespread cortical areas. The rostral intralaminar nuclei innervate dorsal parts of the prefrontal cortex, i.e. the dorsal parts of the prelimbic, anterior cingular and dorsal agranular insular cortical fields, the lateral and ventrolateral orbital areas, and the caudal part of the ventral anterior cingular cortex. Additional projections are aimed at the agranular fields of the motor cortex and the caudal part of the parietal cortex. The lateral part of the parafascicular nucleus sends fibres predominantly to the lateral agranular field of the motor cortex and the rostral part of the parietal cortex. The medial part of the parafascicular nucleus projects rather sparsely to the dorsal part of the prelimbic cortex, the anterior cingular cortex and the medial agranular field of the motor cortex. Individual midline and intralaminar thalamic nuclei are thus in a position to directly influence circumscribed areas of the cerebral cortex. In combination with previously reported data on the organization of the midline and intralaminar thalamostriatal projections and the prefrontal corticostriatal projections the present results suggest a high degree of differentiation in the convergence of thalamic and cortical afferent fibres in the striatum. Each of the recently described parallel basal ganglia-thalamocortical circuits can thus be expanded to include projections at both the cortical and striatal levels from a specific part of the midline and intralaminar nuclear complex. The distinctive laminar distributions of the fibres originating from the different nuclei emphasize the specificity of the midline and intralaminar thalamocortical projections.

Organization of the output of the ventral striatopallidal system in the rat: Ventral pallidal efferents

The efferent projections of the ventral pallidum in the rat were studied using anterograde tracing of Phaseolus vulgaris-leucoagglutinin and retrograde tracing of choleratoxin subunit B. The main aim of this study was to determine the degree of topographical organization in the outputs of the ventral pallidum. In the telencephalon, ventral pallidal fibers reach the prefrontal cortex, the ventral striatum, the lateral septum, the basolateral, lateral, and central amygdaloid nuclei, and the lateral entorhinal area. Diencephalic targets of ventral pallidal fibers are the lateral hypothalamus, the reticular nucleus of the thalamus, the mediodorsal thalamic nucleus, the dorsomedial part of the subthalamic nucleus, the medial part of the parafascicular nucleus and the lateral habenula. In the mesencephalon, ventral pallidal fibers terminate in the ventral tegmental area, the substantia nigra, the retrorubral area, the median raphe nucleus, the nucleus raphe magnus, the peribrachial area, the ventromedial part of the central gray substance and the locus coeruleus. The results of the experiments in which retrograde tracers were injected in different nuclei in the mesencephalon allow the distinction of two main areas in the ventral pallidum. Deposits of retrograde tracers in the substantia nigra, pars reticulata result in labeling of cells in the dorsolateral part of the ventral pallidum, located immediately ventral to the anterior limb of the anterior commissure. Retrograde tracer injections in other targets of the ventral mesencephalon, i.e. the dopaminergic cell groups A10, A9 or A8, or nuclei in the peribrachial area result in labeling of neurons in an extensive ventromedial and ventrolateral zone of the ventral pallidum. The medial part of this ventral pallidal zone projects to the ventral tegmental area, whereas ventral and lateral parts connect with more lateral and caudal mesencephalic targets. The projections from the ventral pallidum to the ventral striatum, the subthalamic nucleus and adjacent lateral hypothalamic area, and the mediodorsal thalamic nucleus are distinctly topographically organized. The ventral pallidostriatal projections preserve a medial-to-lateral, a dorsal-to-ventral and, to a lesser degree, a rostral-to-caudal topography. With respect to the subthalamic region, the dorsolateral part of the ventral pallidum projects to the dorsomedial part of the subthalamic nucleus, whereas the ventromedial and ventrolateral parts of the ventral pallidum are topographically connected with the area of the lateral hypothalamus medially adjacent to the subthalamic nucleus.(ABSTRACT TRUNCATED AT 400 WORDS)

The prefrontal cortex and the integration of sensory, limbic and autonomic information

Publisher Summary This chapter discusses an overview of the afferent and efferent connections of the prefrontal cortex (PFC) in primates and rats, and discusses in the light of this circuitry, the presumptive functional role of the PFC in integrating sensory, motor, cognitive, emotional and autonomic functions. While studying the connectivity of the PFC in rats and primates, it is found that the PFC directly projects to the cholinergic forebrain system, and the monoaminergic cell groups in the hypothalamus and brainstem. In this way, the PFC is in a unique position to influence the transmitter systems that modulate large parts of the forebrain. Further, the PFC subserves visceral functions by direct reciprocal connections with the hypothalamus and brainstem structures, such as the periaqueductal grey and the nucleus of the solitary tract. The PFC is crucial for its role in complex cognitive and behavioral functions. It is postulated that the interoceptive component of the afferents of the PFC may serve as a form of navigational marker in the organization of complex goal-directed behavior.