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O Steward

Publications and source records attributed to O Steward.

At least 19 recordsLinked to original sources
PubMed1992

Lesion-induced synapse reorganization in the hippocampus of cats: sprouting of entorhinal, commissural/associational, and mossy fiber projections after unilateral entorhinal cortex lesions, with comments on the normal organization of these pathways.

This study evaluates whether three forms of sprouting occur in the hippocampus of the cat following unilateral entorhinal cortex (EC) lesions: (1) sprouting of projections from the EC contralateral to the lesion; (2) sprouting of the commissural/associational system; and (3) sprouting of mossy fibers. Tract tracing techniques were used to define the normal organization of the entorhinal cortical projection system, the commissural/associational (C/A) systems, and the mossy fiber projections in normal cats. The same techniques were then used to evaluate whether there were changes in these projections in animals with long-standing unilateral EC lesions. The projections from the entorhinal cortex were evaluated autoradiographically following injections of 3H proline into the entorhinal area. The projections of the C/A system were traced using the Fink-Heimer technique after lesions of the hippocampal commissures, and by using autoradiographic techniques after injections of 3H proline into the hippocampus. The distribution of mossy fibers was evaluated using the Timm's stain. The results reveal that unilateral lesions of the EC in cats lead to the same sorts of sprouting that have been described in rats. There is: (1) an increase in the density of the crossed projection from the surviving EC to the contralateral dentate gyrus that had been deprived of its normal EC inputs; (2) an expansion of the terminal field of the C/A projection system into portions of the molecular layer of the dentate gyrus normally occupied by EC projections; and (3) an increase in supragranular mossy fibers in some animals. The mossy fiber sprouting was especially prominent when the lesions encroached upon the hippocampus. The studies also reveal additional details about the normal organization of hippocampal pathways in cats. The most important points are: (1) there is a crossed projection from the entorhinal cortex to the contralateral dentate gyrus; and (2) there is a complex laminar organization of the commissural and associational terminal fields in the molecular layer of the dentate gyrus that appears to be related to the point of origin of the projections along the septotemporal axis of the hippocampus. This heretofore unrecognized aspect of the laminar organization of C/A terminations has important implications for the temporal competition hypothesis, which has been advanced to account for the development of these afferent systems.

Animals↗
PubMed1992

Signals that induce sprouting in the central nervous system: sprouting is delayed in a strain of mouse exhibiting delayed axonal degeneration.

This study evaluates whether CNS sprouting is initiated by signals related to the degeneration of presynaptic axons. We evaluate the time course of sprouting of cholinergic septohippocampal fibers after unilateral entorhinal cortex (EC) lesions in a substrain of mice carrying a mutation which leads to a substantial delay in the onset of Wallerian degeneration. We first verified that axonal degeneration resulting from EC lesions was delayed in mutant mice using silver-staining techniques (the Fink-Heimer method). Cholinergic sprouting was then evaluated using a histochemical technique for acetylcholinesterase (AChE) in mutant mice and normal controls. In normal control mice, both axonal degeneration and cholinergic sprouting occurred with a time course that was comparable to that described in rats. Argyrophilic degeneration debris was prominent by 4 days postlesion, and increases in AChE staining in the molecular layer of the dentate gyrus were well developed by 10 days. In mice carrying the "Ola" mutation, however, argyrophilic degeneration debris was not detectable at 4 or 6 days postlesion, began to appear in the dentate gyrus by 8 days postlesion, but did not become prominent until 12 days. Increases in AChE staining in the molecular layer of the dentate gyrus were not detectable even at 12 days postlesion, but developed gradually after 14 days. These results demonstrate that the signals which initiate at least one form of CNS sprouting are related to the degeneration of presynaptic axons.

Acetylcholinesterase↗
PubMed1992

Getting the message from the gene to the synapse: sorting and intracellular transport of RNA in neurons.

A key question in cellular neurobiology is how neurons target molecules to cellular microdomains at a distance from the nucleus. Of special importance are the thousands of postsynaptic sites that form the basis for synaptic communication. Recent evidence suggests that an important aspect of molecular trafficking involves differential sorting, selective intracellular transport, and docking of particular mRNA molecules and associated protein synthetic machinery at postsynaptic sites. This offers the potential for local regulation of the production of key proteins in response to conditions at individual synapses. This article reviews what is known about the mechanisms of mRNA trafficking in neurons and in other cells ranging from oocytes to oligodendrocytes, and considers the possible role that mRNA trafficking and the resulting local synthesis of particular proteins may play in cellular function.

Animals↗
PubMed1992

Temperature-dependent blockade of nucleocytoplasmic transport of newly synthesized RNA in neurons.

This study evaluates the temperature sensitivity of transport of recently synthesized RNA from the nucleus to the cytoplasm (nucleocytoplasmic transport) in CNS neurons. Rat hippocampal slices were incubated with [3H]uridine for 1 h to label recently synthesized RNA. Slices were then fixed immediately or maintained at 27 degrees C or 37 degrees C for chase intervals of 3, 4.5, and 6 h to allow for nucleocytoplasmic transport of recently synthesized RNA. The time-dependent translocation of recently synthesized RNA was evaluated autoradiographically. At the end of the 1 h pulse at either 27 degrees C or 37 degrees C, the label was localized exclusively over nuclei. In slices maintained at 37 degrees C, labeling expanded to cover the cell body and proximal dendrites. However, in slices that were labeled and maintained at room temperature, labeling remained confined to the nucleus. In slices that were pulse-labeled at room temperature, and then transferred to 37 degrees C medium, cytoplasmic labeling increased as a function of time. Nucleocytoplasmic transport of RNA in cultured rat hippocampal neurons showed a comparable temperature sensitivity. The inhibition of nucleocytoplasmic transport of RNA at room temperature provides an opportunity to evaluate neuronal function when no new RNA molecules can reach the cytoplasm.

Animals↗
PubMed1992

Seizures and the regulation of astroglial gene expression.

Seizures are known to induce dramatic alterations in neuronal gene expression. These changes may play a role in the genesis of an epileptic state. The present report describes another consequence of seizures-a dramatic induction of glial fibrillary acidic protein (GFAP) expression in astrocytes. Using a hippocampal kindling model, we demonstrate that kindled seizures lead to many fold increases in mRNA for GFAP in structures which experience electrographic seizures. The increases can be detected 1 day following a single seizure. If seizures are induced repetitively (every other day for many days), levels of GFAP mRNA remain elevated. However, when kindled seizures are not induced, levels of GFAP mRNA return to near control levels within a few days. The increases in GFAP mRNA levels are not in response to decreases in neuronal activity (as a result of postictal depression), because GFAP mRNA levels are unaffected when neuronal activity is decreased by blocking afferent drive (with tetrodotoxin). The induction of GFAP expression by seizures may reflect the first step in a process in which seizures induce astrocytic hypertrophy. The changes in astrocytes could in turn modify the way in which astrocytes maintain homeostasis in the extracellular microenvironment in ways that could contribute to the development of an epileptic state.

Animals↗
PubMed1992

Demonstration of local protein synthesis within dendrites using a new cell culture system that permits the isolation of living axons and dendrites from their cell bodies.

The presence of polyribosomes within dendrites suggests a capability for local dendritic protein synthesis. However, local synthesis is difficult to evaluate because of rapid somatodendritic protein transport. The present study describes a two-surfaced culture system that allowed the separation of living axons and dendrites from their cell bodies of origin. Because this system eliminates the transport of proteins produced in the cell body, it was possible to study the extent of dendritic protein synthesis directly. Hippocampal neurons were plated on a Nucleopore polycarbonate membrane that was mounted on a thick matrix of proteins (Matrigel) fixed on a coverslip. As the neurons grew, axons and dendrites grew through the membrane into the Matrigel. To evaluate local protein synthesis within dendrites, the membrane with the cell bodies was removed, leaving a dense array of transected dendrites and axons on the coverslip with few contaminant cell bodies. Absence of cell bodies was confirmed by staining with the nuclear stain Hoechst 33258. Coverslips with isolated neurites were pulse labeled with 3H-leucine for 30 min, and fixed for autoradiography to identify sites of protein synthesis. Autoradiographic analyses revealed that isolated dendrites (immunochemically identified using antibodies against MAP2) became heavily labeled, whereas axons exhibited little if any labeling. The labeling was essentially eliminated when the neurites were pulse labeled with 3H-leucine in the presence of puromycin, whereas labeling was affected only minimally by chloramphenicol. The puromycin-sensitive incorporation of 3H-leucine in dendrites demonstrates that the polyribosomes previously described are active in protein synthesis. This system will allow a characterization of synthetic activity within isolated neurites and provide a new approach to identifying proteins that are produced within dendrites.

Animals↗
PubMed1991

Selective localization of polyribosomes beneath developing synapses: a quantitative analysis of the relationships between polyribosomes and developing synapses in the hippocampus and dentate gyrus.

Previous studies have revealed that polyribosomes are selectively localized beneath post-synaptic sites on central nervous system (CNS) neurons, and are particularly prominent during periods of synapse growth. The present study evaluates whether polyribosomes are most prominent at a consistent time in the developmental history of the synapse, or instead at a consistent time in the life of the organism regardless of the state of synaptic maturation (suggesting a globally acting factor). We compare the time course of synaptogenesis and the association between polyribosomes and developing synapses in three regions that develop at different rates: the external and internal blades of the dentate gyrus, and the CA1 region of the hippocampus proper. Each region was examined electron microscopically at 1, 4, 7, 10, 15, 20, 28 and over 120 days of age, evaluating: (1) synapse density (the number of synaptic profiles/area of neuropil), (2) the width of the neuropil layers, (3) the proportion of synapses with underlying polyribosomes, and (4) the number of polyribosome-containing synapses/area of neuropil. As anticipated on the basis of the differences in cytogenesis, the time course of synaptogenesis was different in the three regions. In the external blade of the dentate gyrus, synapse density increased in a nearly linear fashion between birth and 15 days of age, and then continued to increase at a somewhat slower rate until 28 days of age. Synapse development in the internal blade was delayed by several days in comparison to the external blade. In CA1, synapse density increased slowly between 1 and 7 days, and then at a rapid rate between 7 and 28 days of age. In all three regions, the proportion of synapses with underlying polyribosomes was highest between 1 and 7 days of age, and then decreased as synapse density increased. However, the peak in the number of polyribosome-containing synapses/unit area of neuropil occurred at different times in the three regions (4-7 days of age in the external blade of the dentate gyrus and in CA1, and 20 days of age in the internal blade). In addition to further defining the relationship between polyribosomes and developing synapses, the present study provides a data base on the time course of synapse development in the hippocampus and dentate gyrus, which will be useful for comparisons with other measures.

Aging↗
PubMed1991

LTP-associated EPSP/spike dissociation in the dentate gyrus: GABAergic and non-GABAergic components.

The induction of long-term potentiation (LTP) in the dentate gyrus (DG) leads to a change in the firing characteristics of the dentate granule cells. This phenomenon, termed EPSP/spike dissociation, is seen in field potential studies as a shift to the left of the E-S curve, in which population spike amplitude is plotted against pEPSP slope at various stimulus intensities. It has been suggested that EPSP/spike dissociation reflects a decrease in feed-forward inhibition. To test this hypothesis, we blocked GABA-A neurotransmission in a circumscribed area of the DG in urethane-anaesthetized rats by inserting a micropipette filled with 8 mM bibuculline methiodide in saline. We then recorded E-S curves from 9 such electrodes and from 8 control electrodes before and after inducing LTP in the perforant path. Bicuculline prevented the LTP-associated leftward shift of the E-S curves. Instead, the E-S curve showed a consistent shift to the right at the bicuculline sites after LTP, reflecting potentiation of the pEPSP without corresponding increases in the population spike amplitude. The results indicate that the EPSP/spike relationship is controlled largely by GABAergic input, and that potentiation of the population spike in the DG depends largely on a change in the EPSP/spike relationship.

Action Potentials↗
PubMed1991

Neuronal activity up-regulates astroglial gene expression.

Neuronal gene expression is known to be modulated by functional activity. This modulation is thought to play a key role in determining the differentiation of developing neurons and regulating the operation of mature neurons. Here we describe a regulation of astroglial gene expression by neuronal activity. We report that intense neuronal activity (electrically induced seizures) in rat hippocampus leads to rapid and dramatic increases in mRNA for glial fibrillary acidic protein (GFAP), an astroglia-specific intermediate filament protein. GFAP mRNA levels increased at sites of stimulation as well as in areas that were synaptically activated by the resultant seizures. When seizures were induced repetitively for many days, levels of GFAP mRNA remained chronically elevated. However, GFAP mRNA returned to control levels within a few days after the cessation of stimulation. The coupling between astroglial gene expression and neuronal activity may be a mechanism through which neuronal activity modulates the function of supporting cells that are responsible for regulating the extracellular microenvironment of the brain.

Animals↗
PubMed1991

Evidence that protein constituents of postsynaptic membrane specializations are locally synthesized: time course of appearance of recently synthesized proteins in synaptic junctions.

Previous studies have led to the hypothesis that some protein constituents of postsynaptic membrane specializations are locally synthesized near postsynaptic sites. The present study focuses on one prediction of this hypothesis, specifically, that if some proteins of the postsynaptic membrane specialization are locally synthesized, then the delay between synthesis and assembly into synaptic junctional membrane could be short. We evaluate the time course of appearance of recently synthesized protein in synaptic junctions by pulse-labeling hippocampal slices maintained in vitro with radiolabeled protein precursors, and then isolating subcellular fractions enriched in synaptic plasma membranes (SPM) and synaptic junctional complexes (SJC). We report that there is no evidence of a delay in the appearance of recently synthesized proteins in SPM and SJC fractions. Labeled proteins could be detected as early as 15 min after the initiation of the pulse-labeling period, and the extent of labeling increased monotonically thereafter. The labeling could not be accounted for by contamination of synaptic membrane fractions with other membranes, because the relative specific activity of the SPM and SJC fractions was the same or higher than that of the less pure fractions from which these synaptic fractions were derived. One-dimensional PAGE-fluorography was used to provide an initial characterization of which proteins were labeled in SJC fractions. We found that the most prominent labeled bands were at apparent molecular weights of approximately 43-44, 55-56, and 60 kd, with more lightly labeled bands at about 38 and 116 kd. In some preparations, there was a labeled doublet at about 36-38 kd. There were also other lightly labeled bands at other molecular weights. These bands were much less heavily labeled than the bands at 43-44, 55-56, and 60 kd, however. There was little labeling in the molecular weight range of the "major psd protein" (the alpha subunit of CAM-kinase), although there was diffuse labeling throughout the 45-52 kd region. These results are consistent with the hypothesis that some of the protein constituents of the postsynaptic junctional complex are synthesized by polyribosomes which are selectively localized beneath synaptic junctions.

Animals↗
PubMed1991

Combination of in situ hybridization and immunocytochemistry to detect messenger RNAs in identified CNS neurons and glia in tissue culture.

We have developed a technique in which immunofluorescence is combined with in situ hybridization using cDNA and RNA probes to assess the expression and distribution of messenger RNAs (mRNA) by neurons and neuroglia in tissue cultures of the rat dentate gyrus. The probes used in this study include a cDNA probe for ribosomal RNA (rRNA) and an RNA probe (cRNA) for glial fibrillary acidic protein (GEAP), an intermediate filament protein subunit expressed by astrocytes in the central nervous system. Both ubiquitous (tubulin) and cell type-specific (MAP-2 and GEAP) antibodies were used to identify neurons and neuroglia in culture. Using this procedure, the mRNA for rRNA was found in the cell bodies and large processes of MAP-2-positive neurons and throughout the cytoplasm of GEAP-positive flat astrocytes. In process-bearing astrocytes, GEAP mRNA is concentrated in the cell body, although some hybridization also occurred in astrocyte cell processes. With this combined in situ hybridization-immunofluorescence technique, the expression and distribution of an mRNA can be examined in different immunocytochemically identified cell types under identical culture and hybridization conditions. It is also possible to determine if there is a differential subcellular distribution of an mRNA in a single cell and if the distribution of the mRNA reflects the distribution of the protein itself. Finally, this technique can be utilized to verify the specificity of probes for cell type-specific mRNAs and to determine appropriate hybridization conditions to produce a specific signal.

Animals↗
PubMed1991

Evidence that protein constituents of postsynaptic membrane specializations are locally synthesized: analysis of proteins synthesized within synaptosomes.

Previous studies have led to the hypothesis that some proteins of the postsynaptic membrane are locally synthesized at postsynaptic sites. To evaluate this hypothesis, synaptosome fractions that included fragments of dendrites were allowed to incorporate labeled amino acid into protein. The labeled synaptosomes were then subfractionated to the level of the synaptic plasma membrane (SPM) and then the synaptic junctional complex (SJC). The specific activity (cpm/microgram protein) of the synaptosome fraction and its subfractions was assessed by scintillation counting and protein assay, and labeled polypeptides were characterized by SDS-PAGE and fluorography. The contribution of mitochondrial and eucaryotic protein synthesis to the overall incorporation was evaluated using cycloheximide (CYC), a eucaryotic protein synthesis inhibitor, and chloramphenicol (CAP), a mitochondrial protein synthesis inhibitor. Both the SPM and the SJC subfractions obtained from labeled synaptosomes contained labeled polypeptides. The SPM from labeled synaptosomes had a specific activity approximately equal to that of other nonmitochondrial membrane components of the synaptosome. Thus, labeling of the SPM was not due to contamination by these other labeled membrane components. The mitochondrial fraction had the highest specific activity of the membrane components of the labeled synaptosome, but the specific activity was reduced by 47% in mitochondrial fractions from CAP-treated synaptosomes, while the specific activity of the SPM was not reduced by this treatment. Thus, SPM labeling is not due to mitochondrial contamination. The specific activity of the detergent-insoluble SJC was comparable to that of the SPM from which it was derived. The possibility of labeling of SPM and SJC by contamination with soluble proteins was assessed by adding labeled soluble proteins to a cold synaptosome preparation that was then subfractionated to obtain the SPM and SJC. There was no detectable binding of labeled soluble proteins to the SPM or SJC. These results support the hypothesis that some synaptic proteins are locally synthesized. Fluorographs of SDS gels of SPM from labeled synaptosomes revealed labeled bands at approximate molecular weights of 14, 18, 26, 28, 36, 38, 42, 45, 55, 60, and 116 kDa. Six of these labeled polypeptides at 38, 42, 45, 55, 60, and 116 kDa were still evident in fluorographs of the synaptic junctional complex from labeled synaptosomes. None of these labeled bands were seen in fluorographs of SPM and SJC from CYC-treated synaptosomes, whereas they were still present in fluorographs of CAP-treated synaptosomes. These labeled polypeptides are therefore produced by eucaryotic ribosomal systems.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Dendritic transport: quantitative analysis of the time course of somatodendritic transport of recently synthesized RNA.

We have previously reported that recently synthesized RNA is selectively transported into the dendrites of hippocampal neurons grown in culture (Davis et al., 1987). The present study provides further details about this transport process, focusing especially on the velocity of transport, by comparing the velocity of dendritic transport of RNA in neurons of different ages and in the branched and unbranched dendrites of individual neurons. In our previous study, we recognized that calculations of transport velocity could be compromised because transport was being evaluated in a population of dendrites of varying lengths. The present study uses a mathematical modeling approach to determine how the morphology of the population of dendrites would affect the analysis of transport velocity. Focusing first on a simple model, we compared the distribution of transported material at various times when all dendrites were of the same length and when the population included dendrites of different lengths. We found that the distance of labeling increased linearly over time when all dendrites were of the same length, but increased with a negatively accelerating curve when dendrites were of different lengths. We then determined the actual distribution of dendritic lengths in cultured hippocampal neurons, based on immunostaining with an antibody directed against the selective dendritic marker, microtubule-associated protein 2 (MAP2). Using a computer model, we calculated the mean distance of transport as a function of time in this population of dendrites, assuming different velocities of transport. The velocity that best fit the measured distances of RNA transport in both 7- and 15-d-old neurons was 11 microns/hr (0.26 mm/d). However, for the dendrites exhibiting the longest distance of labeling, the best-fitting curve assumed a velocity of 21 microns/hr in both 7- and 15-d-old neurons (0.50 mm/d). Comparisons of transport in branched and unbranched dendrites revealed that the distance of labeling over branched dendrites was consistently longer than over unbranched dendrites of individual neurons. However, neurons with a larger proportion of branched dendrites did not exhibit a greater mean distance of transport. The density of silver grains was higher over branched than over unbranched dendrites, suggesting that a greater amount of recently synthesized RNA may be transported into branched dendrites. Taken together, these results suggest that RNA transport into dendrites is regulated differentially in the dendrites of individual neurons.

Animals↗
PubMed1979

Functional effects of lesion-induced plasticity: long term potentiation in formal and lesion-induced temporodentate connections.

The crossed temporodentate pathway from the entorhinal cortex of one hemisphere which proliferates in response to a contralateral entorhinal lesion in adult rats was analyzed for its ability to exhibit long term potentiation of synaptic efficacy similar to that which occurs in the normal ipsilateral temporodentate pathway. It was found that while the small synaptic response evoked by contralateral entorhinal cortical stimulation in normal rats does not undergo long term potentiation, after unilateral entorhinal lesions and proliferation of the crossed temporodentate pathway, the crossed pathway acquires a capacity for potentiation of synaptic action which qualitatively resembles that of the normal ipsilateral temporodentate circuit. However, despite the potentiation of synaptic drive, no long term enhancement of cell discharge was observed in the re-innervated dentate gyrus even through potentiation of this parameter was very prominent in the ipsilateral pathway. Mechanisms are discussed by which a previously non-potentiating pathway may acquire, as a consequence of lesion-induced sprouting, an ability to undergo long term potentiation of synaptic efficacy in a fasion similar to the ablated pathway. Reasons for the failure to observe potentiation of cell firing are also considered.

Acetylcholinesterase↗
PubMed1979

Synapses as associative memory elements in the hippocampal formation.

This report analyzes long term potentiation (LTP) and associative interactions between synapses of the ipsilateral and crossed entorhinal cortical (EC) pathways to the dentate gyrus (DG). In the anesthetized rat, conditioning stimulation to one EC-DG pathway reliably elicits LTP at the ipsilateral synapses, while the synapses of the collateral, crossed pathway to the contralateral DG do not exhibit LTP. Furthermore, in the DG ipsilateral to the conditioning stimulation the convergent crossed pathway from the contralateral side, which had not been itself conditioned, failed to exhibit heterosynaptic LTP. These results are consistent with a specific 'synaptic' localization of the changes responsible for LTP, and suggest that some critical number of synapses must be activated in order to observe LTP. While the crossed EC-DG projection never exhibited LTP when conditioned alone, the crossed input could be potentiated under certain circumstances. Specifically, paired conditioning of ipsi- and contralateral inputs by nearly simultaneous conditioning stimulation of the EC bilaterally results in LTP in the crossed system. Furthermore, this associatively induced LTP of the crossed system can be reversed by subsequent conditioning of the ipsilateral system alone. Successive potentiating and depotentiating sequences are possible using paired and non-paired stimulation procedures even after lesions which prevent neural loops through the EC. The results are interpreted as evidence for a 'Hebb' type synapse which has the capability for erasure. This synaptic type is not appropriate for classical conditioning without appendant circuitry, but is suited for other forms of associative learning.

Animals↗
PubMed1979

Analysis of the habituation-like changes in transmission in the temporodentate pathway of the rat.

Habituation-like decrements in extracellular measures of synaptic activation (population EPSP) and cell discharge (population spike) were analyzed in the dentate gyrus of the rat following repetitive low-frequency stimulation of the medial and lateral entorhinal cortex. Stimulation of either subdivision of the entorhinal projection system resulted in comparable habituation-like response decrements with similar stimulation regimens. However, habituating stimulation of one subdivision did not result in decreased responsiveness to stimulation of the other. Repetitive low-frequency stimulation or even a single pulse delivered to either subdivision did, however, result in a potentiation of granule cell discharge in response to stimulation of the other subdivision (a form of heterosynaptic potentiation). This heterosynaptic potentiation of granule cell discharge was not accompanied by any increase in the extracellular EPSP. Comparisons of the relationship between the population EPSP and population spike before and during habituating stimulation revealed changes in cell discharge in response to the habituating stimulus which could not be accounted for by changes in synaptic activation alone. The results suggest that repetitive activation of the temporodentate pathway alters granule cell output as a result of two processes, a habituation-like decrement in synaptic activation, and a potentiation of granule cell discharge as a consequence of prior activation.

Afferent Pathways↗
PubMed1978

Polysynaptic activation of the dentate gyrus of the hippocampal formation: an olfactory input via the lateral entorhinal cortex.

The possibility that olfactory input is transmitted to specific subregions of the hippocampal formation via the entorhinal cortex was investigated electrophysiologically by analyzing the laminar profiles of potentials evoked in the hippocampal formation by stimulation of the lateral olfactory tract (LOT). LOT stimulation resulted in long latency (14--20 ms) evoked responses in the dentate gyrus of the hippocampal formation ipsilateral to the stimulation. The variable long latency of these responses and their inability to follow stimulus rates of 40/s suggested that these potentials reflected polysynaptic activation. Analysis of the laminar profiles of the evoked potentials indicated that the responses originated from a synaptic field localized in the outer portion of the stratum moleculare of the dentate gyrus, a terminal distribution which overlaps that of the lateral entorhinal cortical (LEC) projection to the dentate gyrus. Lesions of the LEC eliminated the long latency responses in the dentate gyrus evoked by LOT stimulation. In addition, a conditioning pulse delivered either to the LOT or to the LEC produced paired pulse potentiation of the response elicited by subsequent stimulation of the other structure. No evidence was found to indicate that responses were generated in regio superior of the hippocampus proper following LOT stimulation. Taken together, these results suggest that stimulation of the LOT activates the dentate gyrus of the hippocampal formation by multisynaptic pathways which relay through the lateral portion of the entorhinal area. This finding is discussed with regard to entorhinal cortical organization and the known olfactory projections to the LEC.

Animals↗