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O Steward

Publications and source records attributed to O Steward.

155 records · Page 9Linked to original sources
PubMed1976

A quantitative autoradiographic and electrophysiological study of the reinnervation of the dentate gyrus by the contralateral entorhinal cortex following ipsilateral entorhinal lesions.

The post-lesion proliferation of contralateral enthorhinal afferents which occurs in response to ipsilateral entorhinal lesions was quantitatively analyzed with autoradiographic and electrophysiological techniques. In both cases, the extent of the crossed projection to the dentate granule cells was quantified on the basis of a contralateral/ipsilateral (C/I) ratio. Autoradiographic measures of grain density in the entorhinal terminal field indicates that the very sparse crossed entorhinal projection in intact animals proliferates approximately 6-fold following unilateral entorhinal lesions (on the basis of an increased C/I ratio of grain density in animals with long standing unilater entorhinal lesions). Furthermore, the total number of grains in the entorhinal terminal zone (obtained by subtracting background from non-terminal regions) also increases approximately 6-fold, indicating that compression of the neuropil cannot be the factor responsible for the increased grain density. These increases in the anatomical extent of the crossed projection as a consequence of unilateral entorhinal lesions are also reflected electrophysiologically. In operated animals, the C/I ratio of the extracellular population EPSP (a measure of the synaptic current generated by the crossed projections) also increase 5-8 fold. In addition, while in normal animals, no population spikes are observed following stimulation of the contralateral entorhinal area (indicating an absence of synchronous grnaule cell discharge in response to contralateral entorhinal input), such population spikes are quite prominent in the reinnervated dentate gyrus, indicating a large increase in the effective synaptic drive of the proliferated crossed projections.

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PubMed1976

Topographic organization of the projections from the entorhinal area to the hippocampal formation of the rat.

The present study re-examines, with autoradiographic methods, the pattern of termination of fibers originating from various medio-lateral divisions of the entorhinal cortex on dentate granule cells and on hippocampal pyramidal cells of the rat. Entorhinal fibers were found to distribute in a proximo-distal gradient along the dendrites of dentate granule cells, with afferents from the medial entorhinal area terminating in the innermost portion of the entorhinal synaptic field, afferents from the lateral entorhinal area terminating in the most superficial portions of the entorhinal synaptic field, and intermediate medio-lateral locations in the entorhinal area terminating in intermediate locations in the entorhinal synaptic zone. A similar graded pattern of termination of medial and lateral entorhinal fibers was apparent in the very slight crossed projection of the entorhinal area to the contralateral dentate gyrus. In addition, a comparable gradient in the pattern of termination of entorhinal fibers was evident in the entorhinal projection field in the distal regions of the pyramidal cells of regio inferior of the hippocampus proper. Entorhinal projections to regio superior were, however, organized in quite a different fashion. In this zone, there was no evidence of a proximo-distal gradient in the patterns of termination of medial and lateral entorhinal areas along the dendrites of regio superior pyramidal cells. Rather, the medio-lateral organization was in a longitudinal dimension, with medial entorhinal afferents terminating in the portions of regio superior near the CA1-CA2 transition, and lateral entorhinal afferents terminating furthest from the CA1-CA2 transition, immediately adjacent to the CA1-subicular transition, and in the molecular layer of the subiculum proper. A comparable longitudinal organization of entorhinal projections to regio superior was also evident in the zones of termination of the crossed temporo-ammonic tract, contralateral to the injection. These results demonstrate a heretofore unrecognized complexity in the patterns of projection of the entorhinal area to the hippocampal formation, and illustrate that the entorhinal cortex cannot be divided into only two discrete divisions on the basis of the pattern of projection.

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PubMedDate not supplied

Behavioral correlates of denervation and reinnervation of the hippocampal formation of the rat: recovery of alternation performance following unilateral entorhinal cortex lesions.

Following unilateral lesions of the entorhinal cortex (E.C.) of the rat, cells in the dentate gyrus which have been deprived of their normal ipsilateral input are reinnervated in part by axons from the contralateral E.C. The proliferation of this crossed projection occurs largely between 8 and 12 days postlesion. The present experiments analyze changes in alternation behavior which occur during this period of afferent proliferation. Rats were trained to alternate responses (L-R) in a T-maze for food reward. Bilateral E.C. lesions resulted in a persistent deficit in alternation performance which did not recover after over 50 days of postoperative testing. Unilateral E.C. lesions, however, resulted in a transient deficit in alternation which recovered over time to preoperative levels. For example, animals permitted a 10-day recovery before the initiation of postlesion testing exhibited no more of a performance deficit than following a 10-day no-training period alone. However, animals permitted only a 3-day postoperative recovery were impaired in the alternation task until 10-12 days postlesion, despite daily training. Thus, recovery of performance following unilateral lesions was dependent on postlesion time rather than the amount of testing/retraining. Since bilateral lesions resulted in a persistent performance deficit while unilateral lesions resulted in a deficit with recovery, we hypothesize that behavioral recovery might be related to the reinnervation of the dentate gyrus by the contralateral E.C. To test this hypothesis, secondary lesions were placed in operated-recovered animals. Secondary lesions of the surviving E.C. resulted in a deficit in alternation performance similar to that following one stage bilateral lesions. In addition, secondary lesions of the dorsal psalterium (the fiber tract which carries the corssed E.C.-dentate projections) also disrupted performance in operated-recovered animals. Primary lesions of the dorsal psalterium alone had only slight and transient effects on alternation performance, however. Thus, the time course of the recovery, the results following bilateral lesions, and the results of secondary lesions are all consistent with the hypothesis that recovery of alternation performance following unilateral E.C. lesions may depend upon the reinnervation of the dentate gyrus by the contralateral E.C.

Afferent Pathways↗
PubMedDate not supplied

Behavioral correlates of denervation and reinnervation of the hippocampal formation of the rat: open field activity and cue utilization following bilateral entorhinal cortex lesions.

Bilateral lesions of the entorhinal cortex (E.C.) of the rat result in persistent deficits in both spontaneous and reinforced alternation. The present study analyzes the nature of this impairment. To determine if changes in exploratory activity accompanied the deficits in alternation, open field activity was measured daily from 2-22 days following bilateral E.C. lesions. Such lesions resulted in a pronounced transient increase in open field activity which peaked between 5 and 7 days postlesion, but subsequently decreased to near preoperative levels at approximately 11 days postlesion. Alternation performance was also analyzed, to determine which cues are utilized to make the alternation, and whether cue utilization is affected by bilateral E.C. lesions. Utilizing a plus (+) maze, animals readily learned to alternate goal arms, but even with extensive training, failed to learn to alternate turns (left and right). However, the ability to identify the two goal arms in a nonalternation situation (which does not require short term recall of the preceding trial) was not permanently impaired by bilateral E.C. lesions. Since bilateral E.C. lesions do not result in persistent deficits in the ability to identify the two goal arms, but do disrupt alternation performance, we hypothesize that the deficit in alternation might reflect an inability to recall which arm was chosen on preceding trials. The implications of these results for an understanding of the behavioral consequences of postlesion reorganization of neuronal circuitry are discussed.

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PubMedDate not supplied

Selective dendritic transport of RNA in hippocampal neurons in culture.

Typical neurons of the central nervous system (CNS) elaborate tens of thousands of membrane specializations at sites of synaptic contacts on their dendrites. To construct, maintain, and modify these specializations, neurons must produce and deliver the appropriate molecular constituents to particular synaptic sites. Previous studies have revealed that polyribosomes are selectively positioned beneath postsynaptic sites, suggesting that in neurons, as in other cell types, protein synthetic machinery is located at or near the sites where particular proteins are needed. The mechanisms that deliver ribosomes and messenger RNA to their specific destinations in cells are therefore of considerable interest. Here we describe a system for RNA transport in dendrites that could provide a mechanism for the delivery of ribosomes and mRNA to synaptic sites in dendrites. Hippocampal neurons grown in culture incorporate 3H-uridine in the nucleus, then selectively transport the newly synthesized RNA into dendrites at a rate of about 0.5 mm day-1. The transport is inhibited by metabolic poisons, suggesting that it is an active, energy-dependent process. The RNA may be transported in association with the cytoskeleton.

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PubMedDate not supplied

Injury-induced physiological events that may modulate gene expression in neurons and glia.

Damage to the brain triggers a host of reactive responses in neurons and glia which are seen at sites of focal injury as well as at sites that are at a distance from the injury. Although many of these responses have been studied extensively, the signals that initiate the different responses have not been fully characterized, and it is still not understood how focal injury affects neurons and glia in distant sites. The present review summarizes recent findings that suggest that physiological events that occur at the time of the injury or during the early postlesion period can play an important and variable role in modulating neuronal and glial responses to injury. We focus on the events that occur in the hippocampal formation following unilateral lesions of the entorhinal cortex - a model system that has been used extensively for studies of cellular responses following focal brain injury. This lesion destroys the cells of origin of a massive excitatory projection to the dentate gyrus and hippocampus proper. Over time, the denervated neurons in the hippocampal formation are almost completely reinnervated as a result of local sprouting of systems that survive the lesion. Thus, this model system has been useful for studying cellular responses to both denervation and reinnervation. We summarize the information that this injury triggers physiological events that can strongly modulate gene expression in neurons and glia, including episodes of spreading depression that occur at the time of the injury, seizures that occur during the early postlesion period, the loss of afferent drive which leads to decreases in postsynaptic activity, and the restoration of activity that occurs in conjunction with reinnervation. We describe recent studies which suggest that some of these physiological events occur to a variable extent in different animals, especially the episodes of spreading depression and the recurrent seizures. Thus, the spatial pattern and temporal dynamics of altered gene expression following this "model" experimental injury may vary from animal to animal. The fact that physiological events strongly modulate the reactive changes in gene expression that occur following injury has important implications for understanding the sequelae of injury, and offers new opportunities for experimental and therapeutic interventions that may improve cellular repair, regeneration, and recovery of function.

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