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G Lynch

Publications and source records attributed to G Lynch.

At least 487 records · Page 27Linked to original sources
PubMed1977

Development of afferent lamination in the fascia dentata of the rat.

In the present study we examine the development of afferent lamination in the fascia dentata of the postnatal rat, as a first step in determining possible mechanisms controlling synaptic specificity in this system. This analysis is based on degeneration-induced argyrophilia as well as autoradiographic labeling of the entorhinal and commissural/associational afferents. Both methods show that in spite of the immaturity of the neonatal fascia dentata, these afferent systems have already established territorial relationships by 4 days of age which persist into adulthood. At 4 days, the entorhinal projection is restricted approximately to the outer 45 mum of the 80 mum wide molecular layer. The commissural/associational projection occupies appoximately the inner 35 mum of the molecular layer. At older ages the commissural/associational zone increases in width very slowly relative to the entorhinal zone. We also discuss these results in relation to potential mechanisms of afferent development and dendritic differentiation.

Afferent Pathways↗
PubMed1977

Patterns of astroglial hypertrophy and neuronal degeneration in the hippocampus of ages, memory-deficient rats.

The brains of aged and young Fischer rats were examined using a modified version of Cajal's gold chloride stain for astrocytes. A sizable loss of pyramidal cells and remarkably hypertrophic astrocytes were found in the hippocampus of the aged animals, while the astrocytic changes were not seen in other forebrain regions. Four major characteristics of the pattern of hippocampal astrogliosis were noted: (1) the astrocytes were often found to be grouped in clusters; (2) grouped astrocytes were commonly seen to have similarly oriented processes; (3) small blood vessels were more often stained in regions of pyramidal cell degeneration and astroglial hypertrophy; and (4) reactive astrocytes were in several instances found to be gathered on the "border" between deteriorated regions and healthier appearing areas. This pattern was interpreted to suggest that the astrocyte clusters may be analogous to senile plaques. Since the aged Fischer animals have previously been found to exhibit retention deficits, the possibility that the hippocampal pathology is related to impaired memory in these animals was raised.

Animals↗
PubMed1977

Impaired monosynaptic potentiation in in vitro hippocampal slices from aged, memory-deficient rats.

Neurophysiological experiments were conducted in vitro on 400 mu thick transverse hippocampal slices from aged and young rats. These slices exhibit neurophysiological responses similar to those of intact hippocampus. The aged rats have previously been found to exhibit impaired retention. Synaptic responses of the Schaffer collateral system were not found to be different between aged and young slices when elicited by very low frequency (0.3 Hz) electrical stimulation. However, the aged slices exhibited marked deficits in frequency and posttetanic potentiation in response to repetitive stimulation (15 Hz). This deficit was interpreted as resulting from an increased tendency to synaptic depression, rather than from impaired potentiation processes. The possibility of a relationship of these physiological deficits in hippocampal synaptic plasticity to the deficits in behavioral plasticity found in these aged animals is considered.

Action Potentials↗
PubMed1976

Potentiation of excitatory synaptic transmission in the normal and in the reinnervated dentate gyrus of the rat.

Following destruction of the ipsilateral temporo-ammonic tract, which originates in the entorhinal cortex, and terminates on the granule cells of the dentate gyrus, fibers from the surviving contralateral entorhinal area proliferate forming extensive new connections with the denervated dentate granule cells. Utlizing extracellular recording techniques, we have compared the characteristics of synaptic transmission in the lesion induced afferents with the characteristics of the normal ipsilateral afferents by analyzing the responses of dentate granule cells to paired pulse activation of temporo-dentate circuitry. In the dentate gyrus of the normal rat, and extracellularly recorded EPSP evoked by stimulation of the ipsilateral entorhinal cortex is enhanced by as much as 100% by a "conditioning" pulse to the same afferent system. This is called paired pulse potentiation. In the reinnervated dentate gyrus, the extracellular EPSP evoked by a test stimulus delivered to the contralateral entorhinal cortex is also potentiated by a conditioning pulse. Thepaired pulse potentiation in the reinnervated dentate gyrus has a time course which is comparable to that of the normal ipsilateral afferent system, but the magnitude of the potentiation is somewhat less, averaging approximately 140% of control...

Afferent Pathways↗
PubMed1976

An electron microscopic study of lesion-induced synaptogenesis in the dentate gyrus of the adult rat. I. Magnitude and time course of degeneration.

Synapses in the rat dentate gyrus are rapidly lost after removal of the primary input from the entorhinal cortex. In this paper we describe the extent and time course of degeneration and in the subsequent paper the nature of the reinnervation processes. They synapses of entorhinal afferents are remarkably concentrated in their zone of termination. Unilateral removal of the rat entorhinal cortex results in the loss of about 86% of all synapses in the outer three-fourths of the molecular layer of the epsilateral dentate gyrus. Entorhinal synapses are all asymmetric (Gray type I) and terminate on dendritic spines. Analysis of the degeneration reaction provides a means to examine the characteristics of the loss of a relatively homogeneous afferent on a single cell type. The morphological characteristics of the the degenerating terminals showed some heterogeneity; both the electron lucent and electron dense types of degenerating terminals were identified. The electron lucent type was observed only at short survival times. The time course of the loss of degenerating terminals was resolvable into two components, each of which followed first order decay kinetics. Thus degenerating entorhinal terminals behaved as a population which disappeared randomly at a rate dependent on the fraction of terminals present at any time. The loss of degenerating terminals was accompanied by the loss of postsynaptic sites. At short survival times the majority of postsynaptic sites (defined by the presence of a postsynaptic density) had disappeared. There was also a loss of complex spines and some shrinkage of the molecular layer.

Animals↗
PubMed1976

An electron microscopic study of lesion-induced synaptogenesis in the dentate gyrus of the adult rat. II. Reappearance of morphologically normal synaptic contacts.

Intact synapses in the denervated area of the rat dentate gyrus are reduced to 14% of those normally present 2-4 days following a unilateral entorhinal lesion. By 160-240 days after lesion, the former entorhinal terminal zone is repopulated with new synapses. In all, there is more than a 5-fold increase in the density of intact synapses in the denervated zone between 2 and 240 days post-lesion, and the denervated zone of the molecular layer is restored to 80% of control values. The synapses are Gray type I and are formed on simple and complex spines which closely resemble those normally present. A few boutons have an abnormally large number of synaptic junctions. Reinnervation seems to progress at differential rates. Synapses are rapidly regained up to 30 days after operation, but thereafter the reacquisition of synaptic connections is much slower. Reinnervation is more rapid in the portion of the denervated zone nearest the granule cells, where the maximal densities are attained within 30 days. The time course of reinnervation differed from that of degeneration. A portion of the new synapses in the reinnervated molecular layer appear to arise by the assembly of new synaptic junctions. Over time, the number of post-synaptic contact sites along a given length of dendritic surface recovers, suggesting the formation of new synaptic sites. Our data indicate that granule cells retain a capacity even into adulthood to manufacture, position and assemble postsynaptic components of a synapse and, in concert with reactive afferents, form normal-appearing synapses.

Animals↗
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.

Animals↗
PubMed1976

Electrophysiological analysis of the projection from the contralateral entorhinal cortex to the dentate gyrus in normal rats.

The projection from the contralateral entorhinal cortex to the dentate gyrus is shown to exert a monosynaptic excitatory action. Stimulation of the contralateral entorhinal cortex evokes unitary granule cell discharges in the dentate gyrus. This evoked activity is followed by a period of inhibition lasting about 50 msec. Laminar analyses of field potentials generated by contralateral medial entorhinal stimulation localize the synaptic activity to the middle portion of the granule cell dendrites. This localization is consistent with the termination site of the contralateral entorhinal projection as previously shown anatomically. Earlier studies have indicated that the entorhinal cortex excites only the ipsilateral dentate gyrus. These findings now demonstrate that the cortical input to the dentate gyrus is bilateral in normal rats. However, the contralateral projection appears to be much less efficacious than the ipsilateral input.

Animals↗
PubMed1976

Changes in the distribution of the dentate gyrus associational system following unilateral or bilateral entorhinal lesions in the adult rat.

The distribution of the dentate gyrus associational system was analyzed in naive adult rats and in those with either unilateral or bilateral lesions of the entorhinal cortex. Horseradish peroxidase histochemistry was used to trace the origin and course of this intrinsic fiber system. The fibers originated in the CA3-4 pyramidal cell field, apparently medial to the origin of the Schaffer collateral system, and followed a trajectory which was essentially identical to that described for this system by Zimmer36. The associational terminal field occupied the inner 26% of the dentate gyrus molecular layer in normal rats and 35-38% of the normal width of that layer following either ipsilateral or bilateral entorhinal lesion. These measurements are quite similar to those previously obtained on the commissural system terminal field in the normal and partially deafferented dentate gyrus. These results are interpreted to reflect axon sprouting by the associational fibers into the adjacent deafferented dendritic field.

Animals↗
PubMed1976

Intracellular responses from granule cell layer in slices of rat hippocampus: perforant path synapse.

Intracellular responses were recorded in vitro from the denate granule cell layer of hippocampal slices prepared from adult rats. Spontaneous activity of granule cells in vitro consisted of action potentials and small, graded depolarizations, presumably of synaptic origin. Granule cells could be activated by injection of depolarizing current or release of hyperpolarizing current. Individual granule cells spatially summed input from the perforant path and fired multiple action potentials in vitro following strong presynaptic volleys. Depolarization decreased and hyperpolarization increased the EPSP amplitude, which is consistent with a conductance-increase mechanism. Although we could demonstrate postexcitatory inhibition in some cells, granule cells in vitro appeared to receive less inhibitory feedback than in vivo, EPSP amplitude and spike output of granule cells showed frequency potentiation and posttetanic potentiation to perforant path stimulation. These intracellular responses in vitro complement some of the findings from field-potential analyses of the dentate gyrus in intact animals.

Action Potentials↗
PubMed1975

Time-dependent changes in commissural field potentials in the dentate gyrus following lesions of the entorhinal cortex in adult rats.

Previous neuroanatomical work has shown that lesions of the entorhinal cortex in adult rats cause the commissural projections to spread from their normally restricted locus in the inner molecular layer approximately 40-50 mum into the outer molecular layer (that is, into the zone deafferented by the lesion). In the present study we measured the effects of the entorhinal lesion on the distribution of short-latency potentials elicited by commissural stimulation in the molecular layer. Studies with animals tested at various times after the lesion and with a preparation that permitted recording from the same rat at several post-lesion intervals both indicated that the commissural response spread 100-150 mum towards the deafferented outer molecular layer, while the maximum response spread 50-100 mum. These effects were first detectable by 9 days after the lesion and were fully developed by 15 days post-lesion. These findings suggest that the growth of the commissural system seen after entorhinal lesions results in the rapid formation of functional terminals and are discussed in relationship to the behavioral consequences of brain lesions.

Animals↗
PubMed1975

A dual marking technique for microelectrode tracks and localization recording sites.

This paper describes techniques for marking both microelectrode tracks and exact recording loci using a combination of fast green dye and horseradish peroxidase (HRP). The procedure involves coating the exterior of HRP filled microelectrodes with fast green dye in order to identify electrode tracks, and ejecting HRP from the electrode to mark recording loci. Rapid, multiple marks can be made with this technique without harming the recording capabilities of the micropipette.

Animals↗
PubMed1975

Neuronal sprouting after hippocampal lesions.

It appears that aberrant but functional circuitry can rapidly develop after removal of particular afferent projections. The parameters describing this process appear to vary according to (1) the age at which the experimental manipulation was performed, (2) the specific afferent being studied, and (3) the particular input which is eliminated or possibly the brain region which is deafferented. It must also be emphasized that abnormal growth is not always found after lesions even in situations which a priori appear appropriate. Hopefully, these anatomical and physiological results obtained in a relatively "simple" brain system will be of help in evaluating the role played by abnormal wiring in the development of behavioral deficits.

Animals↗