Noradrenergic antagonists mitigate amphetamine-induced recovery.

Brain injury, including that due to stroke, leaves individuals with cognitive deficits that can disrupt daily aspect of living. As of now there are few treatments that shown limited amounts of success in improving functional outcome. The use of stimulants such as amphetamine have shown some success in improving outcome following brain injury. While the pharmacological mechanisms for amphetamine are known; the specific processes responsible for improving behavioral outcome following injury remain unknown. Understanding these mechanisms can help to refine the use of amphetamine as a potential treatment or lead to the use of other methods that share the same pharmacological properties. One proposed mechanism is amphetamine's impact upon noradrenaline (NA). In the current, study noradrenergic antagonists were administered prior to amphetamine to pharmacologically block α- and ß-adrenergic receptors. The results demonstrated that the blockade of these receptors disrupted amphetamines ability to induce recovery from hemispatial neglect using an established aspiration lesion model. This suggests that amphetamine's ability to ameliorate neglect deficits may be due in part to noradrenaline. These results further support the role of noradrenaline in functional recovery. Finally, the development of polytherapies and combined therapeutics, while promising, may need to consider the possibility that drug interactions can negate the effectiveness of treatment.

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.

A rodent model for investigating the neurobiology of contralateral neglect.

BACKGROUND: Contralateral neglect is a common and disabling sequela of right hemisphere strokes. Neglect involves attentional and cognitive deficits, including distortions of contralateral spatial and personal awareness. There are no established successful therapies for neglect, and treatment is often complicated by anosognosia. The disturbances associated with neglect are debilitating to patients and their families, and presence of neglect is a strong predictor of poor prognosis for recovery. OBJECTIVE: The present report reviews findings from 20 years of research using a rat model of neglect. In the rat, 2 cortical areas that are linked by corticocortical connections have been identified as having a major role in neglect, and these correspond to frontal and parietal fields in primates. These 2 cortical areas also have convergent projections to the dorsocentral striatum, which has been implicated as a crucial subcortical component of the cortical-striatal-thalamic circuitry involved in directed attention and neglect. We discuss the role of the dorsocentral striatum in neglect and recovery and present evidence that induced axonal sprouting may promote functional recovery following cortical lesions that produce neglect. CONCLUSIONS: The rodent model of neglect captures some of the essential behavioral and anatomic features of neglect in humans. This model has helped reveal the pathophysiology of neglect, has suggested a crucial role of the striatum in recovery from neglect, and is being used to investigate potential therapeutic approaches.

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 micro g 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.

Topographic organization of the striatal and thalamic connections of rat medial agranular cortex.

The rostral and caudal portions of rat medial agranular cortex (AGm) play different functional roles. To refine the anatomical framework for understanding these differences, axonal tracers were used to map the topography of the connections of AGm with the striatum and thalamus. The striatal projections follow mediolateral and rostrocaudal gradients that correspond to the locations of the neurons of origin within AGm. Projections from rostral AGm are widespread and dense rostrally, then coalesce into a circumscribed dorsocentral region at the level of the pre-commissural septal nuclei. Projections from mid and caudal AGm are less widespread and less dense, and are focused more caudally. Striatal projections from the adjacent anterior cingulate and lateral agranular areas overlap those of AGm but are concentrated more medially and laterally, respectively. Thalamic connections of AGm are organized so that more caudal portions of AGm have connections with progressively more lateral and caudal regions of the thalamus, and the full extent of AGm is connected with the ventrolateral (VL) nucleus. Rostral AGm is interconnected with the lateral portion of the mediodorsal nucleus (MD1), VL, and the central lateral (CL), paracentral (PC), central medial, rhomboid and ventromedial nuclei. Caudal AGm has robust connections with VL, the posterior, lateral posterior and lateral dorsal nuclei, but little or none with MD1, CL/PC and VM. These differences in the subcortical connections of rostral and caudal AGm parallel their known differences in corticocortical connections, and represent another basis for experimental explorations of the functional roles of these cortical territories.

Light deprivation produces a therapeutic effect on neglect induced by unilateral destruction of the posterior parietal cortex in rats.

Light deprivation has been found to produce accelerated recovery from severe multimodal neglect induced by unilateral destruction of medial agranular cortex, the rat analog of area 8 in humans. However, neglect in humans is most often produced by destruction of the parietal association cortex. Therefore, the present study examined whether light deprivation would produce accelerated recovery from severe multimodal neglect induced by unilateral destruction of the rodent analog of the parietal association cortex. Subjects received unilateral parietal association cortex lesions, and 4 h after surgery were tested for neglect of visual, tactile, and auditory stimuli. If severe neglect was obtained, subjects experienced either light deprivation, constant light, or a 12:12 light/dark cycle for 48 h. The results indicated that, relative to the other groups, the light deprivation group demonstrated significant accelerated recovery from neglect. Recovery was evident on the first post-light deprivation behavioral test, and was maintained for the 3 weeks of behavioral testing. The results provide further support for the therapeutic effects of light deprivation on neglect induced by cortical lesions when light deprivation is administered in the immediate postoperative period.

Disconnection of medial agranular and posterior parietal cortex produces multimodal neglect in rats.

Two cortical areas in rats have been found to be important in directed attention and spatial processing: the medial agranular cortex (AGm), the rodent analog of the frontal eye fields; and the posterior parietal cortex (PPC), the rodent analog of area 7 in primates. As in primates, unilateral destruction of either of these cortical association areas produces severe contralesional neglect of visual, auditory, and tactile stimulation. AGm and PPC are reciprocally interconnected by longitudinally oriented axons traveling in layer VI of the cortex. Their trajectory provides a unique opportunity to examine the effects of disconnection of these two areas. The key question is whether these two regions function independently or as components of a cortical network for directed attention. Unilateral disconnection of the PPC and AGm was achieved via transverse knife-cuts extending through layer VI of cortex, and the disconnection verified by tract-tracing methods. The knife-cuts produced severe multimodal neglect and allesthesia/allokinesia. The deficits produced by the knife-cuts were virtually identical to those produced by unilateral destruction of these regions. The control operates, which received knife-cuts that spared the interconnections between the AGm and PPC, were unimpaired. The results indicate that AGm and PPC in rats function as parts of a cortical system for directed attention.

Apomorphine produces an acute dose-dependent therapeutic effect on neglect produced by unilateral destruction of the posterior parietal cortex in rats.

The neglect syndrome is a complex and devastating neurological disorder typically induced by unilateral destruction of one of three regions of the neocortex: the inferior parietal lobule, the dorsolateral prefrontal cortex or the cingulate cortex. Previous studies of neglect using a rodent model have indicated that disruption of dopaminergic mechanisms may underlie neglect. However, the pharmacological results were obtained using a rodent prefrontal model of the syndrome (medial agranular cortex), whereas the majority of cases of neglect in humans are produced by unilateral destruction of the posterior parietal cortex (inferior parietal lobule). The present study examined the effects of administration of the dopamine receptor agonist apomorphine on neglect induced by unilateral destruction of the posterior parietal cortex (PPC) in rats. The results indicated that administration of apomorphine produced a significant dose-dependent decrease in the severity of neglect. The results support the contention that neglect induced by cortical damage may be produced by a disruption of dopaminergic mechanisms, and that the PPC may be one component of a cortical system for directed attention.

Neuronal connections of orbital cortex in rats: topography of cortical and thalamic afferents.

The cortical and thalamic afferent connections of rat orbital cortex were investigated using fluorescent retrograde axonal tracers. Each of the four orbital areas has a distinct pattern of connections. Corticocortical connections involving the ventral and ventrolateral orbital areas are more extensive than those of the medial and lateral orbital areas. The medial orbital area has cortical connections with the cingulate, medial agranular (Fr2) and posterior parietal (PPC) cortices. The ventral orbital area has connections with the cingulate area, area Fr2, secondary somatic sensory area Par2, PPC, and visual areas Oc2M and Oc2L. The ventrolateral orbital area (VLO) receives cortical input from insular cortex, area Fr2, somatic sensory areas Par1 and Par2, PPC and Oc2L. The lateral orbital area has cortical connections limited to the agranular and granular insular areas, and Par2. Thalamic afferents to the four orbital fields are also topographically organized, and are focused in the submedial and mediodorsal nuclei. The ventrolateral orbital area receives input from the entirety of the submedial nucleus, whereas the other orbital areas receive input from its periphery only. Each orbital area is connected with a particular segment of the mediodorsal nucleus. The medial orbital area receives its principal thalamic afferents from the parataenial nucleus, the dorsocentral portion of the mediodorsal nucleus, and the ventromedial portion of the submedial nucleus. The ventral orbital area receives input from the lateral segment of the mediodorsal nucleus, the rostromedial portion of the submedial nucleus, and the central lateral nucleus. Thalamic afferents to the ventrolateral orbital area arise from the entirety of the submedial nucleus and from the lateral segment of the mediodorsal nucleus. The lateral orbital area receives thalamic afferents from the central segment of the mediodorsal nucleus, the ventral portion of the submedial nucleus, and the ventromedial nucleus. The paraventricular, ventromedial, rhomboid and reuniens nuclei also provide additional input to the four orbital areas. The connections of the ventrolateral orbital area are interpreted in the context of its role in directed attention and allocentric spatial localization. The present findings provide anatomical support for the view that areas Fr2, PPC and VLO comprise a cortical network mediating such functions.

D1-class dopamine receptor involvement in the behavioral recovery from prefrontal cortical injury.

Following unilateral aspiration of the left medial agranular cortex (AGm) region of prefrontal cortex, rats demonstrate contralateral neglect, characterized by a failure to orient to visual, tactile and auditory stimuli presented on the contralateral body side. While dopamine (DA) has been implicated in cortical neglect and its recovery, this study specifically examined D1-class DA receptors for their involvement in spontaneous recovery from neglect caused by AGm ablation. In the first experiment, left AGm-ablated rats demonstrated severe neglect of contralateral stimuli of each modality which spontaneously recovered over a period of several weeks. Recovered rats were given 7.0 micrograms/kg (s.c.) of the D1-selective antagonist SCH 23390. SCH 23390 reinstated severe neglect of contralateral stimuli, yet had no effect on orientation to ipsilateral stimuli. The same dose had no effect on the orientation behavior of controls. In a second experiment, D1 receptor characteristics were quantified via binding of [3H]SCH 23390 to tissue homogenates of the caudate-putamen of recovered AGm-ablated rats. Numbers and affinities of striatal D1 receptors of rats with unilateral AGm ablations did not differ between hemispheres or from values obtained from lesioned controls. Considered together, these findings indicate that recovery from neglect produced by cortical injury is associated with an increased dependence on D1-class receptor-mediated events, and that this increased dependence is unlikely to be mediated through changes in D1-class receptor numbers or affinities within caudate-putamen.

Bilateral destruction of the ventrolateral orbital cortex produces allocentric but not egocentric spatial deficits in rats.

Previous studies have implicated the ventrolateral orbital cortex (VLO) in spatial attention and orientation. Unilateral destruction of the VLO has been found to produce severe multimodal neglect to unilateral stimulation which is qualitatively quite similar to that found following unilateral destruction of either the medial agranular or posterior parietal cortices. A series of anatomical studies have shown that the VLO is reciprocally interconnected with both the medial agranular cortex and the posterior parietal cortex, which are involved in egocentric and allocentric spatial processing respectively. However, the role of the VLO in either egocentric or allocentric spatial processing has never been directly examined. The present study directly examined the role of the VLO in spatial learning by examining the effects of bilateral VLO destruction on performance in both egocentric (adjacent-arm maze task) and allocentric (cheeseboard task) spatial tasks. Subjects in either the cheese board task or the adjacent arm maze were given presurgical maze training and then were assigned to one of three surgical groups: a bilateral VLO group, a lesion control group which received bilateral destruction of the laterally adjacent lateral orbital cortex which has a quite different pattern of connectivity than the VLO, or a sham operated control group. The results indicated that the VLO operates were significantly impaired in the cheeseboard task (allocentric task) relative to controls, but displayed no deficits in the adjacent-arm maze (egocentric task), a pattern of results similar to those found for the posterior parietal cortex. The results of the present study strongly support the contention that the VLO is a component of the cortical circuitry for spatial processing in rodents.

Rat posterior parietal cortex: topography of corticocortical and thalamic connections.

Anatomical and functional findings support the contention that there is a distinct posterior parietal cortical area (PPC) in the rat, situated between the rostrally adjacent hindlimb sensorimotor area and the caudally adjacent secondary visual areas. The PPC is distinguished from these areas by receiving thalamic afferents from the lateral dorsal (LD), lateral posterior (LP), and posterior (Po) nuclei, in the absence of input from the ventrobasal complex (VB) or dorsal lateral geniculate (DLG) nuclei. Behavioral studies have demonstrated that PPC is involved in spatial orientation and directed attention. In the present study we used fluorescent retrograde axonal tracers primarily to investigate the cortical connections of PPC, in order to determine the organization of the circuitry by which PPC is likely to participate in these functions, and also to determine how the topography of its thalamic connections differs from that of neighboring cortical areas. The cortical connections of PPC involve the ventrolateral (VLO) and medial (MO) orbital areas, medial agranular cortex (area Fr2), portions of somatic sensory areas Par1 and Par2, secondary visual areas Oc2M and Oc2L, auditory area Te1, and retrosplenial cortex. The secondary visual areas Oc2L and Oc2M have cortical connections which are similar to those of PPC, but are restricted within orbital cortex to area VLO, and within area Fr2 to its caudal portion, and do not involve auditory area Te1. The cortical connections of hindlimb cortex are largely restricted to somatic sensory and motor areas. Retrosplenial cortex, which is medially adjacent to PPC, has cortical connections that are prominent with visual cortex, do not involve somatic sensory or auditory cortex, and include the presubiculum. We conclude that PPC is distinguished by its pattern of cortical connections with the somatic sensory, auditory and visual areas, and with areas Fr2, and VLO/MO, in addition to its exclusive thalamic connectivity with LD, LP and Po. Because recent behavioral studies indicate that PPC, Fr2 and VLO are involved in directed attention and spatial learning, we suggest that the interconnections among these three cortical areas represent a major component of the circuitry for these functions in rats.

Light deprivation produces accelerated behavioral recovery of function from neglect produced by unilateral medial agranular prefrontal cortex lesions in rats.

Environmental manipulations involving 48 h of light deprivation have been found to produce sparing of function from neglect produced by unilateral destruction of the medial agranular prefrontal cortex (AGm) in rats. The present study is an extension of these findings and examined whether light deprivation would produce recovery in subjects with demonstrated severe neglect produced by unilateral AGm destruction. The orientation behavior of the subjects, 25 left and 16 right AGm operates, was tested at 4 h post injection and if severe neglect was demonstrated, the subjects were placed into one of three environmental conditions: (1) 48 h of total light deprivation, (2) 48 h of continuous light, or (3) 48 h of a 12:12 light/dark cycle. The left vs. right hemisphere comparisons indicated that the left hemisphere operates were significantly more responsive by 4 h postsurgery than the right hemisphere operates, and only five of the right hemisphere operates demonstrated severe neglect. Therefore, the effects of environment on behavioral recovery of function were only examined in left AGm operates with severe neglect. The results indicated that 48 h of light deprivation could produce dramatic behavioral recovery in left AGm operates with demonstrated severe neglect, and that these effects were not produced by disruption of the light/dark cycle.

Comparisons of hemi-inattention produced by unilateral lesions of the posterior parietal cortex or medial agranular prefrontal cortex in rats: neglect, extinction, and the role of stimulus distance.

Neglect in human and non-human primates has been demonstrated following unilateral lesions of both posterior parietal and prefrontal areas. While it has now been well established that a unilateral lesion of the rodent analog of dorsolateral prefrontal cortex, medial agranular cortex (AGm), results in neglect, the effects of unilateral damage restricted to rodent posterior parietal cortex (PPC) have not been examined in detail. The current study assessed rats with unilateral lesions of PPC or AGm on their ability to orient to unilateral and bilateral stimulation. Since it has been proposed in both the primate and rodent literatures that frontal areas may be responsible for the perception of near space while parietal areas may be responsible for far space, stimuli were presented at two different distances. Lesions of PPC and AGm resulted in severe neglect relative to control operates, with both PPC and AGm operates manifesting severe hemi-inattention and allesthesia relative to control operates. After behavioral recovery from neglect there was no evidence of extinction to bilateral simultaneous stimulation. While neglect to visual stimuli predominated in unilateral PPC operates, unilateral AGm operates had severe neglect in all modalities. In addition, while both left and right PPC operates showed contralesional neglect, AGm operates demonstrated the lateralized differences in neglect reported in previous studies. All groups demonstrated an approximately equivalent level of neglect to stimuli presented at the two different distances, and thus failed to support the suggestion of a peripersonal-extrapersonal dichotomy between frontal and parietal areas in rodents.

Spatial deficits and hemispheric asymmetries in the rat following unilateral and bilateral lesions of posterior parietal or medial agranular cortex.

Studies of spatial behavior in both the human and non-human primate have generally focused on the role of the posterior parietal and prefrontal cortices and have indicated that destruction of these regions produce allocentric and egocentric deficits, respectively. The present study examined the role of the rodent analogs of these regions, the posterior parietal (PPC) and medial agranular (AGm) cortices, in egocentric and allocentric spatial processing, and whether spatial processing in rodents is organized in a hemispatial and/or lateralized manner as has been found in the primate. Eighty male rats receiving either a unilateral or bilateral lesion of AGm or PPC were examined on an egocentric (adjacent arm) or an allocentric (cheeseboard) maze task. The results indicated that PPC and AGm have dissociable spatial functions. Bilateral AGm destruction resulted in egocentric spatial deficits, and unilateral AGm operates demonstrated an intermediate deficit. In contrast, bilateral PPC operates demonstrated a severe deficit in allocentric processing. In addition, there were lateralized differences in the performance of unilateral PPC operates. While right PPC lesions resulted in a significant deficit on the allocentric task, no such deficit was seen in left PPC operates. In addition, neither unilateral AGm nor unilateral PPC operates demonstrated a hemispatial impairment on either the egocentric or allocentric tasks.

Thalamocortical connections of rat posterior parietal cortex.

The neuronal connections of rat posterior parietal cortex (PPC) have been examined using retrograde fluorescent axonal tracers. We have found that PPC receives thalamic input predominantly from the lateral posterior and lateral dorsal nuclei, and not from the ventrobasal nucleus, which projects to the rostrally adjacent hindlimb cortex, or from the dorsal lateral geniculate nucleus, which projects to the caudally adjacent visual association area. PPC has reciprocal corticocortical connections with medial agranular cortex and orbital cortex; together, these three cortical areas may function as a network for directed attention in rats.

Topographic organization in the corticocortical connections of medial agranular cortex in rats.

Medial agranular cortex (AGm) is a narrow, longitudinally oriented region known to have extensive corticortical connections. The rostral and caudal portions of AGm exhibit functional differences that may involve these connections. Therefore we have examined the rostrocaudal organization of the afferent cortical connections of AGm by using fluorescent tracers, to determine whether there are significant differences between rostral and caudal AGm. Mediolateral patterns have also been examined in order to compare the pattern of corticocortical connections of AGm to those of the laterally adjacent lateral agranular cortex (AGl) and medially adjacent anterior cingulate area (AC). In the rostrocaudal domain, there are notable patterns in the connections of AGm with somatic sensorimotor, visual, and retrosplenial cortex. Rostral AGm receives extensive afferents from the caudal part of somatic sensorimotor area Par I, whereas caudal AGm receives input largely from the hindlimb cortex (area HL). Middle portions of AGm show an intermediate condition, indicating a continuously changing pattern rather than the presence of sharp border zones. The whole of the second somatic sensorimotor area Par II projects to rostral AGm, whereas caudal AGm receives input only from the caudal portion of Par II. Visual cortex projections to AGm originate in areas Oc1, Oc2L and Oc2M. Connections of rostral AGm with visual cortex are noticeably less dense than those of mid and caudal AGm, and are focused in area Oc2L. The granular visual area Oc1 projects almost exclusively to mid and caudal AGm. Retrosplenial cortex has more extensive connections with caudal AGm than with rostral AGm, and the agranular and granular retrosplenial subregions are both involved. Other cortical connections of AGm show little or no apparent rostrocaudal topography. These include afferents from orbital, perirhinal, and entorhinal cortex, all of which are bilateral in origin. In the mediolateral dimension, AGm has more extensive corticocortical connections than either AGl or AC. Of these three neighboring areas, only AGm has connections with the somatic sensorimotor, visual, retrosplenial and orbital cortices. In keeping with its role as primary motor cortex, AGl is predominantly connected with area Par I of somatic sensorimotor cortex, specifically rostral Par I. AGl receives no input from visual or retrosplenial cortex. Anterior cingulate cortex has connections with visual area Oc2 and with retrosplenial cortex, but none with somatic sensorimotor cortex. Orbital cortex projections are sparse to AGl and do not appear to involve AC.(ABSTRACT TRUNCATED AT 400 WORDS)