Traumatic brain injury produces impairments in long-term and recent memory.

Traumatic brain injury (TBI) in humans typically produces neurological suppression and a longer lasting impairment of memory clinically defined as post-traumatic amnesia. An animal model that reliably reproduces the physiological changes associated with TBI was used to assess the memory deficits following brain injury. Prior to TBI, rats were trained to perform one of four tasks that assessed either motor performance, long-term or recent memory. Rats were randomly assigned to one of three groups (anesthesia only, sham operation or fluid percussion). Following fluid percussion, used to produce TBI, rats were tested for 6 test sessions. The first session occurred 1-2 min after the experimental manipulation. The next 5 sessions followed the training schedule maintained prior to experimental manipulation. Differences in long-term memory occurred only in the first post-operative test session. Differences in recent memory performance were found across all 6 test sessions. The memory deficits were clearly dissociated from motor deficits. The similar memory deficits observed following human head injury and the experimentally produced TBI injury demonstrate that fluid percussion is a useful approach to examine underlying neurobiological mechanisms involved in head injury and possible clinical interventions.

Primate supplementary eye field. II. Comparative aspects of connections with the thalamus, corpus striatum, and related forebrain nuclei.

The supplementary eye field (SEF) was defined electrophysiologically in behaving monkeys to study its connections with the diencephalon and corpus striatum. The specificity of SEF pathways was determined with horseradish peroxidase (HRP) histochemistry to compare its connections with those of the arcuate frontal eye field (FEF), contiguous dorsocaudal area 6 (6DC), and primary motor cortex (M1, arm/hand region). Results indicate that patterns of SEF connectivity were similar to the FEF and markedly different from areas 6DC and M1. Primary reciprocal thalamic pathways of the SEF were with the magnocellular ventral anterior (VA) nucleus, medial parvicellular VA, medial area X, and paralaminar medialis dorsalis (multiformis and parvicellularis). FEF showed similar connections but its most robust pathway was with MD rather than VA. In contrast, area 6DC showed the most extensive reciprocal connections with lateral VApc and lateral area X with only sparse connections with paralaminar MD. Area 6DC also exhibited reciprocal connections with the ventral lateral (VL) complex and the ventral posterior lateral nucleus, pars oralis (VPLo). M1 showed dense bidirectional connections with VPLo, and to a lesser extent, with VL. M1 pathways with the medial dorsal nucleus were negligible. All areas exhibited connections with the paracentral and central lateral nuclei and only M1 lacked connections with the central superior lateral nucleus. SEF and FEF exhibited similar efferent projections to the caudate and putamen. In the caudate, terminal fields were restricted to a central longitudinal core while those from area 6DC were more widely distributed. Eye field efferents were restricted to the putamen's face region while 6DC projections were more exuberant. The arm/hand region of M1 projected to the arm/hand region of the putamen. Pathways are discussed with respect to their significance in oculomotor control.

Quantitative cytoarchitectural analysis of cellular degeneration in the dorsal lateral geniculate nuclei of cats and kittens with cerebral hemispherectomy.

Quantitative morphometry was used to study the effects of maturationally dependent responses to brain trauma on the cytologic organization of the dorsal lateral geniculate nucleus (LGd). The left hemitelencephalon was removed in adult cats and in neonatal kittens and resultant changes in cell size and density were compared between these groups and with intact controls. Morphological changes were found bilaterally in all lesioned cats. Ipsilaterally, geniculate volume was reduced by 23% in kitten-lesioned cats and by 33% in adult-lesioned cats. The geniculate of both lesion groups contained fewer neurons in all laminae than did the nucleus of intact cats, but only the adult-lesioned cats showed a substantial increase in glial cell counts. Contralaterally, there was a tendency for a lower neuronal density in both lesion groups, but this was significant only for the A-laminae of adult-lesioned cats. Therefore, neonatal lesions spared more neurons bilaterally and produced minimal ipsilateral gliosis compared to the adult ablation. Results are discussed within the context of the "Gudden effect" which asserts that there is more retrograde degeneration in neonatal versus adult brain-lesioned animals.

Primate supplementary eye field: I. Comparative aspects of mesencephalic and pontine connections.

WGA-HRP was used to examine projections to the brainstem from the supplementary eye field (SEF). The SEF was defined electrophysiologically in awake, behaving monkeys and connections were compared to those of the arcuate frontal eye field (FEF), area 6DC, and primary motor cortex. The SEF was found to have either direct or indirect connections with almost every known pre- and paraoculomotor structure of the brainstem. The SEF was found to project bilaterally to layers I and IV of a tangentially widespread region of the superior colliculus. Terminal label was evident in the pretectal olivary nucleus, nucleus of the optic tract, nucleus raphe interpositus (omnipause region), nucleus prepositus hypoglossi, the perioculomotor cap of the central gray, dorsal central gray, nucleus reticularis tegmenti pontis, nucleus reticularis pontis oralis, and to multiple nuclei of the basis pontis (most densely to the dorsomedial nucleus). Bilateral projections were found in the parvicellular red nucleus. Reciprocal connections were present in the nucleus limitans, the mesencephalic reticular formation, locus coeruleus, and the serotonergic nuclei of the raphe complex (dorsalis and central superior). Overall patterns of connectivity were similar to those of the FEF and markedly different from those of the contiguous dorsocaudal area 6 or primary motor cortex. It was concluded that observed patterns of SEF-brainstem connectivity further justifies viewing this region as a distinct eye field that is likely to serve preparatory and trigger functions in the generation of saccadic eye movements.

Transplantation of fetal frontal cortex onto degenerating thalamus of cats and kittens.

Tissue from fetal frontal cortex survived after transplantation onto the surface of the left thalamus in 2 kittens and 2 adult cats which 7 days previously had sustained a left cerebral hemispherectomy. There were nerve fiber connections with host tissue (WGA-HRP, Loyez myelin stain) only in the neonatal animals. The grafts contained surviving neurons in all but in one adult cat which survived 301 days. The grafts had little effects on the retrograde ventral thalamic degeneration typically seen following hemispherectomy. However, the dorsal lateral geniculate nucleus adjacent to the transplants showed reduced neuronal loss and gliosis compared to controls. Magnetic resonance imaging was successfully used to visualize the grafts in vivo and suggested a decrease in size as well as changes in composition for a graft systematically followed for 120 days posttransplantation. Cytochrome oxidase histochemistry indicated sustained metabolic activity in transplants containing surviving neurons. This study introduces the cat as a useful model for brain tissue transplantation in a classical, myelinated sensorimotor system.

Direct projection from the supplementary eye field to the nucleus raphe interpositus.

Using WGA-HRP we have demonstrated that a direct projection links the supplementary eye field, but not the more caudal aspect of the supplementary motor area, to the brain stem omnipause region. Findings are discussed in relation to oculomotor control.

Organization of geniculocortical connections following prenatal interruption of binocular interactions.

The organization of geniculostriate connections in normal cats was compared with that of adult animals that were uniocularly enucleated before birth. In normal animals microelectrophoretic deposits of horseradish peroxidase conjugated to wheat germ agglutinin (WGA-HRP) into the A-lamina of the dorsal lateral geniculate body (LGd) resulted in anterograde label in layers IV and VI and labeled cells in layer VI of areas 17 and 18. The labeling pattern within both of these cortical areas consisted of alternating patches separated by zones of equivalent size that were relatively free of label. In the normal animals no reaction product was evident in any other cortical area. In the prenatally enucleated cats, the LGd both contralateral and ipsilateral to the remaining eye is comprised of only two distinct cell layers. The dorsal layer appears to be a composite of the normal A/A1-laminae, while the ventral layer appears to correspond to the C-laminae. Deposits of WGA-HRP into the superficial aspect of the A/A1 layer yielded a dense continuous band of label within layers IV and VI of areas 17 and 18. Additionally, such deposits in the prenatally enucleated cats also revealed an anomalous reciprocal connection with area 19. Punctate deposits of WGA-HRP into cortical area 19 of the fetal enucleates resulted in the labeling of two distinct populations of cells within the A/A1 layer of the LGd. No cells were labeled within the A-laminae following such deposits into area 19 of normal animals. The geniculocortical connections of the prenatally enucleated cats, including that to area 19, were found to be retinotopically organized. These results indicate that in utero interruption of binocular interactions prevents the formation of ocular dominance domains within areas 17 and 18 of the cat's visual cortex. This could reflect the maintenance of exuberant geniculocortical projections present at the time of prenatal eye removal as originally suggested by Rakic (Science, 214 (1981) 928-931). The anomalous connection with area 19, on the other hand, could be due to the disruption of LGd cell migration resulting from the early eye removal.

Functional organization of the cat's visual cortex after prenatal interruption of binocular interactions.

The functional consequences of interrupting in utero binocular interactions were studied by recording from single cells in area 17 of adult cats that had one eye removed at least 2 wk before birth. In these animals all cortical neurons could be driven by the remaining eye, and in tangential microelectrode penetrations, sequences of neurons containing a full 180-degree cycle of preferred orientations were encountered. Other response properties of cortical neurons in the prenatally enucleated animals were also normal with the notable exception that the dimensions of receptive fields were significantly smaller when compared with those of control animals. Our results indicate that orientation columns in the visual cortex can develop independently of ocular dominance columns, and they suggest that interruption of binocular interactions during prenatal development of the visual pathways may enhance the resolving power of the remaining eye.

An analysis of the transport of WGA-HRP in the cat's visual system.

The increasing use of WGA-HRP as a neuroanatomical tracer has led us to examine two aspects of its uptake and transport. Microelectrophoretic deposits of WGA-HRP were centered in lamina A of the LGd to determine whether or not there is a discrepancy between the size of the deposit site and the effective uptake zone. For this purpose, the size of the deposit site was compared to the area of labeled ganglion cells in the retina. It was found that the effective uptake zone is approximately one half the size of the geniculate area containing reaction-product. Deposits of WGA-HRP in the optic tract, optic radiations and corpus callosum were made in order to determine if this tracer is incorporated and transported by intact fibers. In no case were labeled axon terminals or neuronal somata observed. However, application of the conjugated enzyme to cut fibers of the corpus callosum resulted in robust labeling.