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Biomedical subjects

E A Murray

Publications and source records attributed to E A Murray.

70 records · Page 4Linked to original sources

A selective mnemonic role for the hippocampus in monkeys: memory for the location of objects.

Monkeys were trained preoperatively on a one-trial learning task in which they were required to associate in memory a novel object and the place in which it had just appeared. After learning the task to a level of 80% correct responses, they received bilateral ablations of either the hippocampal formation or the amygdaloid complex. The monkeys with amygdalectomy showed a small drop in performance initially but then regained their preoperative level. By contrast, the monkeys with hippocampectomy dropped to near-chance levels of performance and remained there throughout postoperative testing. Both groups performed at better than 90% correct responses on a test of recognition memory. These results, taken together with earlier work, suggest that although the hippocampus and amygdala appear to participate equally in object recognition, only the hippocampus is critical for the rapid formation of object-place associations.

Animals↗

Cortical connections of the somatosensory fields of the lateral sulcus of macaques: evidence for a corticolimbic pathway for touch.

The ipsilateral corticocortical connections of the somatosensory fields of the lateral sulcus of macaques were examined with both anterograde and retrograde axonal transport methods. In most cases, the field of interest was identified prior to the injection of the tracer substance by recording neuronal responses to somatic stimulation. The results show that the second somatosensory area (S2) is reciprocally connected with the retroinsular area (Ri), area 7b, and the granular (Ig) and dysgranular (Id) insular fields. Ri is also reciprocally connected with Ig. Previously reported connections were confirmed between S2 and areas 3a, 3b, 1, and 2 and between area 5 and both area 7 and Ri. Moreover, the portions of Ig and Id that receive somatic inputs were shown to project to the amygdaloid complex. Id projects, in addition, to the perirhinal cortex, which supplies input to the hippocampal formation. The corticocortical projections were found to have two distinct laminar patterns of termination. One is characterized by heavy terminations in layers IV and IIIb and the other by heavy terminations in layer I, but no terminations in layers IV and IIIb. These two patterns were typically found to be reciprocally related. The results suggest that somatosensory information is processed by a series of cortical fields, including areas 3a, 3b, 1, 2, 5, 7b, S2, Ig, and Id. These fields have access to the amygdaloid complex and the hippocampal formation. Thus, a ventrally directed tactile processing pathway can be followed from S1 to the temporal lobe limbic structures via relays in S2 and the insula; this corticolimbic pathway may subserve tactile learning and memory.

Animals↗

Thalamic connectivity of the second somatosensory area and neighboring somatosensory fields of the lateral sulcus of the macaque.

The thalamocortical relations of the somatic fields in and around the lateral sulcus of the macaque were studied following cortical injections of tritated amino acids and horseradish peroxidase (HRP). Special attention was paid to the second somatosensory area (S2), the connections of which were also studied by means of thalamic isotope injections and retrograde degeneration. S2 was shown to receive its major thalamic input from the ventroposterior inferior thalamic nucleus (VPI) and not, as previously reported, from the caudal division of the ventroposterior lateral nucleus (VPLc). Following small injections of isotope or HRP into the hand representation of S2, only VPI was labeled. Larger injections, which included the representations of more body parts, led to heavy label in VPI, with scattered label in VPLc, the central lateral nucleus (CL), and the posterior nucleus (Po). In addition, small isotope injections into VPLc did not result in label in S2 unless VPI was also involved in the injection site, and ablations of S2 led to cell loss in VPI. Comparison of injections involving different body parts in S2 suggested a somatotopic arrangement within VPI such that the trunk and lower limb representations are located posterolaterally and the hand and arm representations anteromedially. The location of the thalamic representations of the head, face, and intraoral structures that project to S2 may be in the ventroposterior medial nucleus (VPM). The granular (Ig) and dysgranular (Id) fields of the insula and the retroinsular field (Ri) each receive inputs from a variety of nuclei located at the posteroventral border of the thalamus. Ig receives its heaviest input from the suprageniculate-limitans complex (SG-Li), with additional inputs from Po, the magnocellular division of the medial geniculate n. (MGmc), VPI, and the medial pulvinar (Pulm). Id receives its heaviest input from the basal ventromedial n. (VMb), with additional inputs from VPI, Po, SG-Li, MGmc, and Pulm. Ri receives its heaviest input from Po, with additional input from SG-Li, MGmc, Pulm, and perhaps VPI. Area 7b receives its input from Pulm, the oral division of the pulvinar, the lateral posterior n., the medial dorsal n., and the caudal division of the ventrolateral n. These results indicate that the somatic cortical fields, except for those comprising the first somatosensory area, each receive inputs from an array of thalamic nuclei, rather than just one, and that individual thalamic somatosensory relay nuclei each project to more than one cortical field.

Afferent Pathways↗

Visual recognition in monkeys following rhinal cortical ablations combined with either amygdalectomy or hippocampectomy.

Performance on a visual recognition task was assessed in cynomolgus monkeys with ablations of rhinal (i.e., ento-, pro-, and perirhinal) cortex in combination with either amygdalectomy or hippocampectomy, as well as in unoperated controls. Removal of the hippocampal formation plus rhinal cortex resulted in a mild recognition deficit, whereas removal of the amygdaloid complex plus rhinal cortex resulted in a severe deficit. Comparison of the results with those of an earlier study (Mishkin, 1978) indicates that adding a rhinal cortical removal to hippocampectomy yields little, if any, additional impairment in recognition. By contrast, adding a rhinal cortical removal to an amygdalectomy has a profound effect; indeed, the recognition impairment in monkeys with amygdaloid plus rhinal removals was at least as severe as that seen in monkeys with combined amygdaloid and hippocampal removals. Taken together, these results support the conclusion that combined damage to the amygdaloid and hippocampal systems is necessary to produce a severe recognition deficit. In addition, they suggest that the effect of ablating the rhinal cortex is equivalent to that of removing the entire hippocampal formation, presumably because the rhinal cortical ablation disconnects the hippocampus from its neocortical input.

Amygdala↗

Amygdalectomy impairs crossmodal association in monkeys.

Monkeys trained on both visual and tactual versions of an object memory task (delayed nonmatching-to-sample) received bilateral ablations of either the amygdaloid complex or the hippocampal formation of the brain. Although both groups performed well on the two intramodal versions (visual-to-visual and tactual-to-tactual), the amygdalectomized monkeys were severely impaired relative to the hippocampectomized monkeys on a crossmodal version (tactual-to-visual). The findings suggest that the amygdala is critical for certain forms of crossmodal association and that the loss of such associations underlies many of the bizarre behaviors that make up the Klüver-Bucy syndrome.

Amygdala↗

Further evidence that amygdala and hippocampus contribute equally to recognition memory.

The medial temporal neuropathology found in an amnesic neurosurgical patient [17] was simulated in monkeys in an attempt to determine whether the patient's mnemonic disorder, which had been ascribed to bilateral hippocampal destruction, may have also been due in part to unilateral amygdaloid removal. For this purpose, monkeys were prepared with bilateral hippocampectomy combined with unilateral amygdalectomy, and (as a control) bilateral amygdalectomy combined with unilateral hippocampectomy. The animals were trained both before and after surgery on a one-trial visual recognition task requiring memory of single objects for 10 sec each and then given a postoperative performance test in which their one-trial recognition ability was taxed with longer delays (up to 2 min) and longer lists (up to 10 objects). The two groups, which did not differ reliably at any stage, obtained average scores on the performance test 75 and 80%, respectively. Comparison with the results of an earlier experiment [8] indicates that this performance level lies approximately midway between that of monkeys with amygdaloid or hippocampal removals alone (91%) and that of monkeys with combined amygdalo-hippocampal removals (60%). The results point to a direct quantitative relationship between degree of recognition impairment and amount of conjoint damage to the amygdala and hippocampus irrespective of the specific structure involved. Evidence from neurosurgical cases tested in visual recognition [21] indicates that the same conclusion may apply to man.

Amygdala↗

Relative contributions of SII and area 5 to tactile discrimination in monkeys.

Rhesus monkeys with ablations of either the second somatosensory cortex (SII) or of the superior parietal lobule (area 5) were tested on a battery of tactile discrimination tasks in order to help determine which of these areas might constitute part of a postulated cortico-limbic tactile processing pathway. Monkeys with ablations of SII were severely impaired on both texture and shape discrimination learning and had markedly elevated size and roughness discrimination thresholds relative to control animals. By contrast, monkeys with area 5 lesions were impaired only on roughness thresholds, and these were elevated only moderately. Although more severe tactile deficits following lesions of area 5 have been reported previously, they were found in the present study only when the area 5 removals were extended slightly rostrally, in a third operated group, to include the posteromedial part of the hand representation of area 2. These results are consistent with the suggestion that SII, but not area 5, is a critical station in a tactile processing pathway that proceeds from the primary somatosensory cortex (SI) to the limbic structures of the temporal lobe through links in SII and the insular cortex.

Animals↗

Severe tactual as well as visual memory deficits follow combined removal of the amygdala and hippocampus in monkeys.

To determine whether medial temporal limbic structures are essential for memory in more than one modality, we trained monkeys preoperatively on both visual and tactual versions of a sensory memory task and then retested them after they had been given bilateral ablations of either the amygdaloid complex, the hippocampal formation, or both. Monkeys with the combined ablations were severely impaired in both modalities. By contrast, the amygdalectomized monkeys were only moderately impaired in the two modalities, while the hippocampectomized monkeys were impaired in neither. Further examination revealed that the source of the impairment in the monkeys with amygdalectomy alone, unlike that in the animals with combined lesions, was the small size of the pool from which the test objects were drawn. The latter result suggests that, whereas the sensory memory impairment following the combined lesions is basically a recognition loss, the more selective impairment following amygdalectomy alone reflects special difficulty in determining whether a recognized object was presented recently. By demonstrating that the profound sensory memory impairment that follows combined ablation of the amygdala and hippocampus extends beyond a single modality, the present results strengthen the proposals that these two structures are important for sensory memory in all modalities and the multimodal or global amnesia observed in patients with medial temporal lobe damage is likewise due to combined amygdaloid and hippocampal lesions.

Amygdala↗

Severe tactual memory deficits in monkeys after combined removal of the amygdala and hippocampus.

Monkeys with bilateral removals of both the amygdaloid complex and hippocampal formation were far more severely impaired on a tactual memory task than were monkeys with removal of either structure alone. These data parallel earlier findings on visual memory in monkeys and suggest that: (i) the memory deficit following combined ablations of the amygdala and hippocampus is multimodal; and (ii) the global anterograde amnesia observed in patients with medial temporal-lobe damage is also due to combined damage to these two structures.

Amygdala↗

Organization of tectospinal neurons in the cat and rat superior colliculus.

Neurons in the superior colliculus which send axons to the spinal cord were identified by the retrograde axonal transport method. Injections of the retrograde axonal tracer, horseradish peroxidase, made into different levels of the cervical spinal cord indicate that the spinally projecting neurons in the superior colliculus are topographically organized. Tectospinal neurons projecting to the rostral segments of the cervical spinal cord are found over a larger extent of the contralateral superior colliculus than those terminating in the cervical enlargement. The tectospinal projection to the cervical enlargement in both rats and cats arises almost exclusively from the caudolateral quadrant of the contralateral superior colliculus, whereas the tectal projection to the rostral (upper) cervical spinal cord originates, in cats, from almost the entire extent of the colliculus and, in rats, from its greater part. No evidence for tectospinal projections to the thoracic or lumbar levels of the spinal cord was found. In the context of the hypothesis that, in these species, head and body movements which orient the animal toward stimuli in its environment may be mediated by the superior colliculus, these data are consistent with the view that direct tectospinal connections may play a role in such movements.

Afferent Pathways↗

Organization of corticospinal neurons in the monkey.

The retrograde axonal transport method has been employed to identify the cell bodies of cortical neurons projecting directly to the spinal cord in the monkey. The investigation has focused on aspects of the laminar, columnar, and somatotopic organization of corticospinal neurons within each of the cytoarchitectural and functional subdivisions of the sensorimotor cortex. The principle findings of these experiments are that: i) cortical regions containing cell bodies of corticospinal neurons are the first motor cortex (area 4), the first somatic sensory cortex (areas 3a, 3b, 1, and 2), and part of the immediately adjacent posterior parietal cortex (area 5), the second somatic sensory cortex, the supplementary motor cortex (the medial aspect of area 6), and the medial part of the posterior parietal cortex in a region termed the supplementary sensory area; ii) corticospinal neurons display a somatotopic organization within each of these functional subdivisions of the sensorimotor cortex; iii) all corticospinal neurons arise from layer V of the cortex; and iv) corticospinal neurons within the first motor and first somatic sensory cortex often occur in clusters, perhaps reflecting a columnar organization in the sensorimotor cortex. These findings demonstrate the origins of the corticospinal system to be more extensive than previously recognized and show that a number of common features characterize the organization of corticospinal neurons in all cortical areas. Across cortical subdivisions, however, major differences exist in the extent of spinal segmental representations, in the manner in which corticospinal neurons occur in groups, and in the numerical density and sizes of corticospinal neurons. These aspects of the organization of the corticospinal system presumably reflect specialization of the different cortical areas in spinal cord sensory and motor control.

Animals↗

Increased expression of nitric oxide synthase and dendritic injury in simian immunodeficiency virus encephalitis.

OBJECTIVES: Widespread dendritic injury may be one mechanism involved in the neurologic impairment that occurs in HIV-1 infection. The objectives of this study were to quantitate the extent of dendritic injury in a primate model of central nervous system (CNS) infection, investigate the role of nitric oxide (NO) as a mediator of neuropathologic changes, and evaluate the relation of these changes to cognitive and motor function. STUDY DESIGN/METHODS: Cognitive and motor function was assessed in rhesus macaque monkeys infected with simian immunodeficiency virus (SIV). In situ hybridization, immunohistochemistry, and quantitative image analysis were employed to assess the relations among productive infection, NO synthase (iNOS), and dendritic injury. RESULTS: Productive infection of cells of the macrophage lineage in CNS is associated with inflammation, increased expression of iNOS, and dendritic injury. The tests of cognitive and motor function employed were abnormal in both animals that had evidence of productive infection and those that did not. CONCLUSIONS: Increased NO accompanying productive infection and encephalitis may be one cause of neuronal injury in lentivirus infections of the CNS. Extension of tests of cognitive and motor function to late-stage AIDS in rhesus monkeys is needed to assess the potential role of NO-induced dendritic damage in lentiviral encephalopathy/AIDS dementia complex.

Animals↗