Dorsocentral Striatum Research Articles

Perceptual spatial position induces the attentional enhancement of prepulse inhibition and its neural mechanism

Prepulse inhibition (PPI) is a sensorimotor gating process that reduces the startling response when a weaker sensory stimulus precedes a sudden startling stimulus. Perceptual spatial separation (PSS) between the prepulse and the background noise was found to enhance PPI compared to perceptual spatial co-location (PSC). However, little is known about the perceptual characteristics of prepulses in the PSS that induce more inhibition of the startling response and the associated neural mechanism. The dorsocentral striatum (DCS) was the convergence of spatial information from the cortical and thalamic circuits. Our study investigated whether the perceptual spatial position of prepulses induced spatial attentional modulation of PPI. In addition, whether the DCS was involved in spatial attentional modulation's neural circuits of PPI. In our study, the relative perceptual image positions of the prepulse and masker were controlled by the playback time difference between the two loudspeakers, i.e., PSS and PSC. The specific spatial attention of the prepulse was conditioned by foot shock. The results revealed that PPI was generally enhanced after fear conditioning/conditioning-control manipulation across all rats. Further enhancement of PPI in the PSS condition occurred only in the fear conditioning position, not in the conditioning-control position. We first found that PPI did not show specific spatial enhancement in the drug-blocking bilateral DCS rats with 2 mM kynurenic acid. These results demonstrated that the perceptual spatial position modulated the spatial attention of prepulse and improved PPI. DCS was involved in the attentional modulation neural circuits of PPI and processed spatial information of prepulse.

Striatal dopamine D1 receptors control motivation to respond, but not interval timing, during the timing task.

Dopamine plays a critical role in behavioral tasks requiring interval timing (time perception in a seconds-to-minutes range). Although some studies demonstrate the role of dopamine receptors as a controller of the speed of the internal clock, other studies demonstrate their role as a controller of motivation. Both D1 dopamine receptors (D1DRs) and D2 dopamine receptors (D2DRs) within the dorsal striatum may play a role in interval timing because the dorsal striatum contains rich D1DRs and D2DRs. However, relative to D2DRs, the precise role of D1DRs within the dorsal striatum in interval timing is unclear. To address this issue, rats were trained on the peak-interval 20-sec procedure, and D1DR antagonist SCH23390 was infused into the bilateral dorsocentral striatum before behavioral sessions. Our results showed that the D1DR blockade drastically reduced the maximum response rate and increased the time to start responses with no effects on the time to terminate responses. These findings suggest that the D1DRs within the dorsal striatum are required for motivation to respond, but not for modulation of the internal clock speed.

A neuronal activation correlate in striatum and prefrontal cortex of prolonged cocaine intake

Maladaptive changes in the involvement of striatal and frontal cortical regions in drug use are thought to underlie the progression to habitual drug use and loss of cognitive control over drug intake that occur with accumulating drug experience. The present experiments focus on changes in neuronal activity in these regions associated with short-term (10 days) and long-term (60 days) self-administration of cocaine. Quantitative in situ hybridization for the immediate early gene Mkp1 was combined with statistical parametric mapping to assess the distribution of neuronal activity. We hypothesized that neuronal activity in striatum would increase in its dorsal part and that activity in frontal cortex would decrease with prolonged cocaine self-administration experience. Expression of Mkp1 was profoundly increased after cocaine self-administration, and the magnitude of this effect was greater after short-term compared to long-term self-administration. Increased neuronal activity was seen in both dorsal and ventral sectors of the striatum after 10 days exposure to cocaine. However, enhanced activity was restricted to dorsomedial and dorsocentral striatum after 60 days cocaine self-administration. In virtually all medial prefrontal and most orbitofrontal areas, increased expression of Mkp1 was observed after 10 days of cocaine taking, whereas after 60 days, enhanced expression was restricted to caudal parts of medial prefrontal and caudomedial parts of orbitofrontal cortex. Our data reveal functional changes in cellular activity in striatum and frontal cortex with increasing cocaine self-administration experience. These changes might reflect the neural processes that underlie the descent from recreational drug taking to compulsive cocaine use.

Unilateral lesions of the dorsocentral striatum (DCS) disrupt spatial and temporal characteristics of food protection behavior.

Spatial and temporal information processing provide a foundation for higher cognitive functions. The survival of animals depends on integrating spatial and temporal information to organize behavior. In general, previous research has focused on only one source of information processing; however, there is evidence to support a convergence in the processing of egocentric-spatial and temporal information within a cortico-striatal system of structures. The current study evaluated the contributions of the dorsocentral striatum (DCS) to egocentric-spatial and temporal (within the seconds-to-minutes range) processing of information using a food protection task. Long-Evans rats received unilateral NMDA lesions of the DCS followed by testing in a food protection task. Performance in this task is mediated by the motivation of the animal to consume a food item, their perception of the time required to consume a food item, their sensory ability to process egocentric cues, and their motor ability to evade an incoming conspecific. Unilateral DCS lesions were shown to impact both spatial and temporal characteristics of food protection. These results suggest that the DCS may be a critical structure for the integration of egocentric-spatial and temporal information within the interval timing range.

Organization of the corticostriatal projection from rat medial agranular cortex to far dorsolateral striatum

The rat medial agranular cortex (AGm) projects bilaterally to the striatum, mainly to the dorsocentral striatum (DCS) and in a narrow band in the far dorsolateral striatum (FDLS). For the projection from AGm to DCS, axonal and synaptic densities are known to be two times greater in the ipsilateral versus contralateral DCS, producing a contralateral to ipsilateral ratio of 0.5. In the present study we wished to determine if this was also the case for the projection from AGm to FDLS. Injections of biotinylated dextran amine were made into AGm in normal rats, and unbiased sampling was used to quantify the density of axons and axonal varicosities present in the FDLS. Unlike the contra/ipsi ratio of 0.5 found in DCS, the FDLS exhibited a contra/ipsi ratio of 1.0 for both axonal and synaptic densities. While overall axonal densities were roughly equivalent in ipsilateral and contralateral FDLS, axonal density in the ipsilateral FDLS was uniform, whereas density in the contralateral FDLS increased from the medial edge of the band to its boundary at the external capsule. These differences in the bilateral projections of AGm to separate striatal regions raise questions regarding the populations of corticostriatal neurons in AGm that contribute to these projections.

Cortical connections of the rat lateral posterior thalamic nucleus

Spatial processing related to directed attention is thought to be mediated by a specific cortical–basal ganglia–thalamic–cortical network in the rat. Key components of this network are associative cortical areas medial agranular cortex (AGm) and posterior parietal cortex (PPC), dorsocentral striatum (DCS), and lateral posterior (LP) thalamic nucleus, all of which are interconnected. Previously, we found that thalamostriatal projections reaching DCS arise from separate populations of neurons of the mediorostral part of LP (LPMR). The far medial LPMR (fmLPMR) terminates in central DCS, a projection area of AGm, whereas central LPMR terminates in dorsal DCS, a projection area of PPC. This represents segregated regional convergence in DCS from different sources of thalamic and cortical inputs. In the present study, thalamocortical and corticothalamic projections arising from and terminating in LPMR and neighboring thalamic nuclei were studied by anterograde and retrograde tracing techniques in order to further understand the anatomical basis of this neural circuitry. A significant finding was that within LPMR, separate neuronal populations provide thalamic inputs to AGm or PPC and that these cortical areas project to separate regions in LPMR, from which they receive thalamic inputs. Other cortical areas adjacent to AGm or PPC also demonstrated reciprocal connections with LP or surrounding nuclei in a topographic manner. Our findings suggest that the cortical–basal ganglia–thalamic network mediating directed attention in the rat is formed by multiple loops, each having reciprocal connections that are organized in a precise and segregated topographical manner.

Posterior parietal cortex as part of a neural network for directed attention in rats

A rodent model of directed attention has been developed based upon behavioral analysis of contralateral neglect, pharmacological manipulations, and anatomical analysis of neural circuitry. In each of these three domains the rodent model exhibits striking similarities to humans. We hypothesize that there is a specific thalamo-cortical-basal ganglia network that subserves spatial attentional functions. Key components of this network are medial agranular and posterior parietal cortex, dorsocentral striatum, and the lateral posterior thalamic nucleus. Several issues need to be addressed before we can hope to realistically understand or model the functions of this network. Among these are the roles of medial versus lateral posterior parietal cortex; cholinergic mechanisms in attention; interhemispheric interactions; the role of synchronous firing at the cortical, striatal, and thalamic levels; interactions between cortical and thalamic projections to the striatum; interactions between cortical and nigral inputs to the thalamus; the role of collicular inputs to the lateral posterior thalamic nucleus; the role of cerebral cortex versus superior colliculus in driving the motor output expressed as orienting behavior during directed attention; the extent to which the circuitry we describe for directed attention also plays a role in other forms of attention.

Topography in the projections of lateral posterior thalamus with cingulate and medial agranular cortex in relation to circuitry for directed attention and neglect

In the rat, the lateral posterior thalamic nucleus (LP) has reciprocal connections with areas of the cortex and the striatum involved in directed attention and its dysfunctional counterpart, contralateral neglect. It has also been shown that the medial portion of the mediorostral part of LP (mLPMR) is of special interest because it has connections with the dorsocentral striatum, a key node in this circuitry. In the present study we used neuroanatomical tracers to map the specific connections and topography of LP with the anterior cingulate cortex (ACC) and medial agranular cortex (AGm). We primarily used Alexa Fluor conjugates of the retrograde tracer cholera toxin subunit B, and injected two different colored conjugates into ACC and AGm in the same animal in order to directly compare the differential topography of the thalamocortical connections of mLPMR. The bidirectional tracer, dextran amine, was also used to examine anterograde corticothalamic projections of AGm and ACC. We found that mLPMR consists of two distinct groups of neurons, with the more dorsal group projecting to ACC and the more ventral group projecting to AGm. This is mirrored by a similar corticothalamic topography. These findings suggest that the ventral mLPMR is specifically associated with AGm and dorsocentral striatum, while dorsal mLPMR is associated with ACC. They also suggest that ACC may play a role in the circuitry for directed attention and contralateral neglect, as it is known to do in humans.

Quantification of synaptic density in corticostriatal projections from rat medial agranular cortex

Medial agranular cortex (AGm) has a prominent bilateral projection to the dorsocentral striatum (DCS). We wished to develop a normal baseline by which to assess neuronal plasticity in this corticostriatal system in rats with neglect resulting from a unilateral lesion in AGm, followed by treatment with agents that promote sprouting and functional recovery in other systems. Injections of biotinylated dextran amine were made into AGm in normal rats, and unbiased sampling was used to quantify the density of axons and axonal varicosities present in DCS (the latter represent presynaptic profiles). Labeling density in contralateral DCS is approximately half of that seen in ipsilateral DCS (this ratio is 0.50 for axons, 0.55 for varicosities). The ratio of varicosities is stable over a greater than seven-fold range of absolute densities. There is no consistent relationship between the absolute density of axons and axon varicosities; however, the ratio measures are strongly correlated. We conclude that changes in the contralateral/ipsilateral ratio of axon density after experimental treatments do reflect changes in synaptic density, but axon varicosities are likely to be the most sensitive anatomical parameter by which to assess plasticity at the light microscopic level.

Striatal projections from the rat lateral posterior thalamic nucleus

The dorsocentral striatum (DCS) has been implicated as an associative striatal area receiving inputs from several cortical areas including medial agranular cortex (AGm), posterior parietal cortex (PPC), and visual association cortex to form a cortical-subcortical circuit involved in directed attention and neglect. The lateral posterior thalamic nucleus (LP) may also play a role in directed attention and neglect because LP has robust reciprocal connections with these cortical areas and projects to DCS. We used anterograde axonal tracing to map thalamostriatal projections from LP and surrounding thalamic nuclei, with a focus on projections to DCS. The thalamic nuclei investigated included LP, laterodorsal thalamic nucleus (LD), central lateral nucleus (CL), and posterior thalamic nucleus (Po). We found that the mediorostral part of LP (LPMR) projects strongly to DCS as well as to the dorsal peripheral region of the striatum. Further, there is topography within LPMR and DCS such that the far medial LPMR projects to the central region of DCS (projection area of AGm) and the central LPMR projects to the dorsal region of DCS (projection area of PPC and Oc2M). In contrast, the laterorostral part of LP (LPLR) and other thalamic nuclei surrounding LP project to dorsolateral to dorsomedial peripheral regions of the striatum but do not project to DCS. These findings indicate that DCS is a region of convergence for thalamostriatal and corticostriatal projections from regions that are themselves interconnected, serving as the key element of the corticostriatal-thalamic network mediating spatial processing and directed attention.

Overlap and interdigitation of cortical and thalamic afferents to dorsocentral striatum in the rat

Dorsocentral striatum (DCS) is an associative region necessary for directed attention in rats. DCS is defined as the main region in which axons from ipsilateral medial agranular cortex (AGm) terminate within the striatum. In this double-labeling study, we placed a green axonal tracer in area AGm and a red one in an additional brain region. We examined the spatial relationship between terminals from area AGm and other portions of the cortical–basal ganglia–thalamic–cortical network involved in directed attention and its dysfunction, hemispatial neglect, in the rat. These include lateral agranular cortex (AGl), posterior parietal cortex (PPC), ventrolateral orbital cortex (VLO), and secondary visual cortex (Oc2M). One important finding is the presence of a dense focus of labeled axons within DCS after injections in cortical area PPC or Oc2M. In these foci, axons from PPC or Oc2M extensively overlap and interdigitate with axons from cortical area AGm. Additionally, retrograde labeling of striatal neurons, along with double anterograde labeling, suggests that axons from cortical area AGm and AGl cross and possibly make contact with the dendritic processes of single medium spiny neurons. Axons from thalamic nucleus LP were observed to form a dense band dorsal to DCS which is similar to that seen following PPC injections, and a significant number of LP axons were also observed within DCS. Projections from thalamic nucleus VL are present in the dense dorsolateral AGm band that abuts the external capsule, are densest in the dorsolateral striatum, and were not observed in DCS. These results extend previous findings that DCS receives input from diverse cortical areas and thalamic nuclei which are themselves interconnected.

The associative striatum: organization of cortical projections to the dorsocentral striatum in rats.

The dorsocentral striatum (DCS) is the major site of input from medial agranular cortex (AGm) and has been implicated as an associative striatal area that is part of a cortical-subcortical circuit involved in multimodal spatial functions involving directed attention. Anterograde axonal tracing was used to investigate the spatial organization of corticostriatal projections to DCS. Injections of biotinylated dextran amine were made into several cortical areas known to project to DCS based on retrograde tracing data. These included areas AGm, lateral agranular cortex (AGl), orbital cortex, posterior parietal cortex (PPC), and visual association cortex. We discovered a previously undescribed geometry whereby the projection from AGm is prominent within DCS and the main corticostriatal projections from areas other than AGm are situated around the periphery of DCS: visual association cortex dorsomedially, PPC dorsally, AGl laterally, and orbital cortex ventrally. Each of these cortical projections is also represented by less dense aggregates of terminal labeling within DCS, organized as focal patches and more diffuse labeling. Because these cortical areas are linked by corticocortical connections, the present findings indicate that interconnected cortical areas have convergent terminal fields in the region of DCS. These findings suggest that DCS is a central associative region of the dorsal striatum characterized by a high degree of corticostriatal convergence.

Infusion of apomorphine into the dorsocentral striatum produces acute drug-induced recovery from neglect produced by unilateral medial agranular cortex lesions in rats

Previous studies have shown that systemic administration of apomorphine is effective in producing acute drug-induced recovery from neglect induced by unilateral medial agranular cortex (AGm) lesions. More recent studies have demonstrated that recovery from neglect may be due to plastic changes occurring in the dorsal central striatum (DCS). Further, lesions of the DCS produce neglect that does not respond to systemic administration of apomorphine, suggesting that this area may be crucial for the therapeutic effects of apomorphine. In the present study, the behavioral effects of apomorphine infused into the DCS of animals with AGm lesion-induced neglect were examined to determine whether the DCS is a site of drug action. An infusion of 0.375 μg of apomorphine into the DCS, but not a lateral striatal control area, was effective in producing acute recovery from neglect. The results of this study support the crucial role of the DCS in recovery from neglect induced by unilateral AGm lesions and suggest that the DCS may be an important site of action for the therapeutic effects of apomorphine. Because dopamine agonist therapy has been shown to be effective in humans with neglect, the results of the current study may represent an important step in the development of future pharmacotherapies.

The associative striatum: cortical and thalamic projections to the dorsocentral striatum in rats

Corticostriatal projections to the dorsocentral striatum (DCS) were investigated using retrograde fluorescent axonal tracing. The DCS is of interest because of its role in directed attention and recovery from multimodal hemispatial neglect following cortical lesions of medial agranular cortex (AGm), an association area that is its major source of cortical input. A key finding was that the multimodal posterior parietal cortex (PPC) also contributes substantial input to DCS. This is significant because PPC and AGm are linked by corticocortical connections and are both critical components of the circuitry involved in spatial processing and directed attention. Other cortical areas providing input to DCS include visual association areas, lateral agranular cortex and orbital cortex. These areas also have reciprocal connections with AGm and PPC. Less consistent labeling was seen in somatic sensorimotor areas FL, HL and Par 1. Thalamic afferents to DCS are prominent from the intralaminar, ventrolateral, mediodorsal, ventromedial, laterodorsal (LD) and lateral posterior (LP) nuclei. Collectively, these nuclei constitute the sources of thalamic input to cortical areas AGm and PPC. Nuclei LD and LP are only labeled with injections in dorsal DCS, the site of major input from PPC, and PPC receives its thalamic input from LD and LP. We conclude that DCS receives inputs from cortical and thalamic areas that are themselves linked by corticocortical and thalamocortical connections. These findings support the hypothesis that DCS is a key component of an associative network of cortical, striatal and thalamic regions involved in multimodal processing and directed attention.

Effects of light deprivation on recovery from neglect and extinction induced by unilateral lesions of the medial agranular cortex and dorsocentral striatum

A number of previous studies have indicated that an environmental manipulation, 48 h of light deprivation (LD), produces virtually complete and permanent behavioral recovery of function from neglect induced by medial agranular cortex (AGm) lesions. LD-induced behavioral recovery from neglect is correlated with physiological changes in the dorsolateral striatum, an area that contains the projection zone of AGm efferents in the dorsocentral striatum (DCS). In this study, the behavioral effects of 48 h of LD on subjects with either unilateral DCS, AGm, or combined AGm/DCS lesions were investigated to examine whether the integrity of the DCS is crucial for behavioral recovery from neglect and whether LD will have a therapeutic effect on extinction deficits. Subjects were tested for extinction to bilateral simultaneous stimulation of the forepaws, and visual, auditory and tactile neglect. Forty-eight hours of LD failed to produce behavioral recovery from neglect in rats with DCS lesions, or a therapeutic affect on extinction deficits in any of the groups. The results of this study further support the crucial role of the DCS in recovery from neglect induced by AGm lesions and suggests that the DCS may be the crucial site for the mechanisms leading to LD-induced recovery. Further, the ineffectiveness of LD on extinction suggests that components of the neglect syndrome are dissociable and may require different therapeutic interventions.

Unilateral destruction of the dorsocentral striatum in rats produces neglect but not extinction to bilateral simultaneous stimulation

A number of previous studies have indicated that lesions of the medial agranular cortex (AGm) in rats induce multimodal neglect and extinction to bilateral simultaneous stimulation (extinction), the two major symptoms of the neglect syndrome in humans. A recent study demonstrated that lesions of dorsocentral striatum (DCS), the site of AGm projections to the striatum, produce multimodal neglect qualitatively similar to that found with AGm lesions. In the present study, the behavioral effects of unilateral DCS lesions were examined in more detail for the major manifestations of neglect: hemineglect, extinction, and allesthesia/allokinesia. Subjects were tested for extinction to bilateral simultaneous stimulation of the forepaws three times a week for 3 weeks. Neglect testing occurred twice weekly and the subjects were tested for the presence of neglect by rating the magnitude of orientation to visual, tactile, and auditory stimulation. The results indicated that DCS operates, while demonstrating severe neglect, failed to demonstrate extinction or allesthesia/allokinesia. These findings suggest that the neural mechanisms that underlie neglect and extinction are dissociable in this system. A better understanding of the neural mechanisms that underlie extinction is particularly important because humans that have recovered from neglect often continue to demonstrate the debilitating symptoms of extinction.

Unilateral destruction of the medial agranular cortical projection zone in the dorsocentral striatum produces severe neglect in rats

Physiological studies have indicated that neglect and recovery from neglect induced by unilateral lesions of the medial agranular cortex (AGm) in rats is correlated with reductions of metabolic activity and plastic changes in glutamate receptors in the dorsolateral quadrant of the striatum. The dorsolateral quadrant of the striatum encompasses the dorsocentral striatum (DCS), the projection zone of AGm efferents. Although these changes in function in the dorsolateral striatum are correlated with neglect and behavioral recovery, direct evidence for the role of this region is lacking. In the present study, we examined the behavioral effects of unilateral destruction of the DCS on neglect, as assessed by orientation to visual, auditory, and tactile stimulation. Subjects received a unilateral N-methyl-d-aspartate lesion of the DCS, a control lesion in a laterally adjacent site in the striatum, or an injection of vehicle into the DCS. The subjects were tested for neglect three times per week for 3 weeks by rating the magnitude of orientation to visual, tactile, and auditory stimulation. The results indicate that the DCS group demonstrated significantly more severe neglect than did the lesion control group or the vehicle controls. The results suggest that the DCS is part of a system for appropriate orientation to sensory stimuli in rats and that the DCS may play a pivotal role in behavioral recovery from neglect produced by AGm lesions.