James V. Corwin

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 Tel, 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.

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.

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. J. Comp. Neurol. 467:271–292, 2003.

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.

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.

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.

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.

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.

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.

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.