Pieter Voorn

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.

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.

Immunohistochemical characterization of the shell and core territories of the nucleus accumbens in the rat.

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 accurnbens, 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.

Increase of enkephalin and decrease of substance P immunoreactivity in the dorsal and ventral striatum of the rat after midbrain 6-hydroxydopamine lesions.

Unilateral 6-hydroxydopamine lesions of the mesostriatal dopaminergic system in the rat resulted in a decrease of substance P-immunoreactivity in the ventral striatum, and in a heterogeneously distributed increase of enkephalin-immunoreactivity in the dorsal and ventral striatum and the globus pallidus. The respective decrease and increase are caused by a lower or higher staining intensity of the peptidergic fibers, whereas no changes were found in the cell bodies.

Corticostriatal Interactions during Learning, Memory Processing, and Decision Making

This mini-symposium aims to integrate recent insights from anatomy, behavior, and neurophysiology, highlighting the anatomical organization, behavioral significance, and information-processing mechanisms of corticostriatal interactions. In this summary of topics, which is not meant to provide a comprehensive survey, we will first review the anatomy of corticostriatal circuits, comparing different ways by which “loops” of cortical–basal ganglia circuits communicate. Next, we will address the causal importance and systems-neurophysiological mechanisms of corticostriatal interactions for memory, emphasizing the communication between hippocampus and ventral striatum during contextual conditioning. Furthermore, ensemble recording techniques have been applied to compare information processing in the dorsal and ventral striatum to predictions from reinforcement learning theory. We will next discuss how neural activity develops in corticostriatal areas when habits are learned. Finally, we will evaluate the role of GABAergic interneurons in dynamically transforming cortical inputs into striatal output during learning and decision making.

Detailed mapping of serotonin 5-HT1B and 5-HT1D receptor messenger RNA and ligand binding sites in guinea-pig brain and trigeminal ganglion : Clues for function

The similar pharmacology of the 5-HT1B and 5-HT1D receptors, and the lack of selective compounds sufficiently distinguishing between the two receptor subtypes, have hampered functional studies on these receptors. In order to provide clues for differential functional roles of the two subtypes, we performed a parallel localization study throughout the guinea-pig brain and the trigeminal ganglia by means of quantitative in situ hybridization histochemistry (using [35S]-labelled riboprobes probes for receptor messenger RNA) and receptor autoradiography (using a new radioligand [3H]alniditan). The anatomical patterns of 5-HT1B and 5-HT1D receptor messenger RNA were quite different. While 5-HT1B receptor messenger RNA was abundant throughout the brain (with highest levels in the striatum, nucleus accumbens, olfactory tubercle, cortex, hypothalamus, hippocampal formation, amygdala, thalamus, dorsal raphe and cerebellum), 5-HT1D receptor messenger RNA exhibited a more restricted pattern; it was found mainly in the olfactory tubercle, entorhinal cortex, dorsal raphe, cerebellum, mesencephalic trigeminal nucleus and in the trigeminal ganglion. The density of 5-HT(1B/1D) binding sites (combined) obtained with [3H]alniditan autoradiography was high in the substantia nigra, superior colliculus and globus pallidus, whereas lower levels were detected in the caudate-putamen, hypothalamus, hippocampal formation, amygdala, thalamus and central gray. This distribution pattern was indistinguishable from specific 5-HT1B receptor labelling in the presence of ketanserin under conditions to occlude 5-HT1D receptor labelling; hence the latter were below detection level. Relationships between the regional distributions of the receptor messenger RNAs and binding sites and particular neuroanatomical pathways are discussed with respect to possible functional roles of the 5-HT1B and 5-HT1D receptors.

Augmented reinforcer value and accelerated habit formation after repeated amphetamine treatment.

Various processes might explain the progression from casual to compulsive drug use underlying the development of drug addiction. Two of these, accelerated stimulus-response (S-R) habit learning and augmented assignment of motivational value to reinforcers, could be mediated via neuroadaptations associated with long-lasting sensitization to psychostimulant drugs, i.e. augmented dopaminergic neurotransmission in the striatum. Here, we tested the hypothesis that both processes, which are often regarded as mutually exclusive alternatives, are present in amphetamine-sensitized rats. Amphetamine-sensitized rats showed increased responding for food under a random ratio schedule of reinforcement, indicating increased incentive motivational value of food. In addition, satiety-specific devaluation experiments under a random interval schedule of reinforcement showed that amphetamine-sensitized animals exhibit accelerated development of S-R habits. These data show that both habit formation and motivational value of reinforcers are augmented in amphetamine-sensitized rats, and suggest that the task demands determine which behavioral alteration is most prominently expressed.

Anatomical evidence for direct connections between the shell and core subregions of the rat nucleus accumbens

The nucleus accumbens is thought to subserve different aspects of adaptive and emotional behaviors. The anatomical substrates for such actions are multiple, parallel ventral striatopallidal output circuits originating in the nucleus accumbens shell and core subregions. Several indirect ways of interaction between the two subregions and their associated circuitry have been proposed, in particular through striato-pallido-thalamic and dopaminergic pathways. In this study, using anterograde neuroanatomical tracing with Phaseolus vulgaris-leucoagglutinin and biotinylated dextran amine as well as single-cell juxtacellular filling with neurobiotin, we investigated the intra-accumbens distribution of local axon collaterals for the identification of possible direct connections between the shell and core subregions. Our results show widespread intra-accumbens projection patterns, including reciprocal projections between specific parts of the shell and core. However, fibers originating in the core reach more distant areas of the shell, including the rostral pole (i.e. the calbindin-poor part of the shell anterior to the core) and striatal parts of the olfactory tubercle, than those arising in the shell and projecting to the core. The latter projections are more restricted to the border region between the shell and core. The density of the fiber labeling within both the shell and core was very similar. Moreover, specific intrinsic projections within shell and core were identified, including a relatively strong projection from the rostral pole to the rostral shell, reciprocal projections between the rostral and caudal shell, as well as projections within the core that have a caudal-to-rostral predominance. The results of the juxtacellular filling experiments show that medium-sized spiny projection neurons and medium-sized aspiny neurons (most likely fast-spiking) contribute to these intra-accumbens projections. While such neurons are GABAergic, the intrastriatal projection patterns indicate the existence of lateral inhibitory interactions within, as well as between, shell and core subregions of the nucleus accumbens.

Gabaa receptor maturation in relation to eye opening in the rat visual cortex

Changes in subunit composition of N-methyl-D-aspartate (NMDA) receptors have been reported to be affected by visual experience and may therefore form a major aspect of neuronal plasticity in the CNS during development. In contrast, putative alterations in the expression and functioning of the inhibitory GABAA receptor around eye opening have not been well defined yet. Here we describe the timing of changes in GABAA receptor subunit expression and the related synaptic functioning in the neonatal rat visual cortex and the influence of visual experience on this process. Quantitative analysis of all GABAA receptor subunit transcripts revealed a marked alpha3 to alpha1 subunit switch, in addition to a change in alpha4 and alpha5 expression. The changes were correlated with an acceleration of the decay of spontaneous inhibitory postsynaptic currents (sIPSCs). Both changes in receptor expression and synaptic functioning were initiated well before eye opening. Moreover, dark rearing could not prevent the robust upregulation of alpha1 or the change in sIPSC kinetics, indicating that this is not dependent of sensory (visual) input. Upon eye opening a positive correlation was observed between a faster decay of the sIPSCs and an increase in sIPSC frequency, which was absent in dark-reared animals. Thus, lack of extrinsic input to the cortex does not affect overall developmental regulation of synaptic functioning of GABAA receptors. However, we cannot exclude the possibility that visual experience is involved in proper shaping of the inhibitory network of the primary visual cortex.

Social play behavior in adolescent rats is mediated by functional activity in medial prefrontal cortex and striatum

Social play behavior is a characteristic, vigorous form of social interaction in young mammals. It is highly rewarding and thought to be of major importance for social and cognitive development. The neural substrates of social play are incompletely understood, but there is evidence to support a role for the prefrontal cortex (PFC) and striatum in this behavior. Using pharmacological inactivation methods, ie, infusions of GABA receptor agonists (baclofen and muscimol; B&M) or the AMPA/kainate receptor antagonist 6,7-dinitroquinoxaline-2,3(1H,4H)-dione (DNQX), we investigated the involvement of several subregions of the medial PFC and striatum in social play. Inactivation of the prelimbic cortex, infralimbic cortex, and medial/ventral orbitofrontal cortex using B&M markedly reduced frequency and duration of social play behavior. Local administration of DNQX into the dorsomedial striatum increased the frequency and duration of social play, whereas infusion of B&M tended to have the same effect. Inactivation of the nucleus accumbens (NAcc) core using B&M increased duration but not frequency of social play, whereas B&M infusion into the NAcc shell did not influence social play behavior. Thus, functional integrity of the medial PFC is important for the expression of social play behavior. Glutamatergic inputs into the dorsomedial striatum exert an inhibitory influence on social play, and functional activity in the NAcc core acts to limit the length of playful interactions. These results highlight the importance of prefrontal and striatal circuits implicated in cognitive control, decision making, behavioral inhibition, and reward-associated processes in social play behavior.