bluuebunny/crossref_metadata_2025_split huggingface dataset:
A presynaptic role for protein kinase C in hippocampal mossy fiber synaptic transmission
Authors: Terrian David M. , Ways D. Kirk , Gannon Robert L. 
Published: May 2005

AbstractIt has been suggested that the maintenance of long‐term potentiation (LTP) in the hippocampal mossy fiber (MF) synapse involves a presynaptic mechanism that does not require the activation of protein kinase C (PKC), since this enzyme appears to be absent in the MF presynaptic terminals. In the present study the authors evaluated this proposal by directly comparing the metabolic properties of hippocampal MF synaptosomes and a conventional P2B synaptosomes preparation prepared from the same hippocampal tissue. Protein kinase C‐dependent histone phosphotransferase activity was found to be comparable in MF and P2B synaptosomes. Western blot analysis was performed using antisera prepared against four of the PKC isoforms, and the results demonstrate that the α, β, and γ PKC isoforms are present in relatively equivalent amounts in these two subcellular fractions. However, the cytosolic fraction derived from the hippocampal MF synaptosomes appeared to contain a greater amount of the PKC−∈ isoform when compared to the P2B synaptosomal preparation. Four distinct endogenous substrates present in the MF synaptosomes are shown to be phosphorylated in response to PKC activation. A functional role for PKC in the hippocampal MF nerve endings seems to be indicated by the finding that 4β‐phorbol 12, 13‐dibutyrate (PDBu) and 4β‐phorbol 12, 13‐diacetate produce a dosedependent potentiation of the K+‐evoked release of endogenous glutamate and dynorphin B, while the inactive 4‐α‐phorbol was without effect. The PDBu‐induced enhancement of transmitter release was blocked by the PKC inhibitor, staurosporine. In addition, PDBu significantly facilitated the rise in cytosolic free calcium that immediately followed depolarization of the MF synaptosomal membrane. It is concluded that hippocampal MF presynaptic terminals possess a variety of PKC isoforms and that their activation may have an important facilitory influence on MF synaptic transmission and plasticity.
Swimming navigation and structural variations of the infrapyramidal mossy fibers in the hippocampus of the mouse
Authors: Schöpke R. , Wolfer D. P. , Lipp H.‐P. , Leisinger‐Trigona M.‐C. 
Published: May 2005

AbstractThe extent of the infrapyramidal mossy fiber projection in CA3 (IIP–MF) at the midsepto‐temporal level correlates negatively with two‐way avoidance learning and positively with performance in the radial maze, both tasks known to be sensitive to hippocampal lesions. If hippocampal structural variations are causing behavioral variations, one must predict positive correlations between the extent of the IIP–MF and performance in swimming navigation. Thus, the authors studied learning and reversal learning of swimming navigation in mice in which the size of the IIP–MF had been randomized by means of systematic crosses and in 2 mouse strains known for differential infrapyramidal projections (C57BL/6 and DBA/2).In 19 random‐bred mice (9 male, 10 female), the extent of the IIP–MF showed negative correlations with swimming time after platform reversal (day 4: r = −0.50, P<.03; day 5: r = −0.73, P>.001), but none during acquisition of the task. In addition, statstical analysis suggested an influence of asymmetrically distributed mossy fiber projections during reversal learning. The strain comparison between 18 DBA/2 and 16 C57BL/6 male mice confirmed these results: no strain difference during days 1–3, and a significantly faster swimming time in the strain C57 BL/6 (with large IIP–MF) at day 5 (second day of reversal), associated with significantly more crossings of the former platform location during the early phases of reversal learning. This latter measure was also negatively correlated with asymmetry of the IIP–MF in both strains. Finally, variations of the IIP–MF were correlated partially with adjustment of swimming speed that appeared to depend on size and asymmetry of CA4 as well. Thus, natural variations in the size of the IIP–MF distribution, and, perhaps, of CA4, appear to linearly influence processes directly involved in complex spatial learning.
Decreased glutamate release correlates with elevated dynorphin content in the hippocampus of aged rats with spatial learning deficits
Authors: Zhang Wan‐Qin , Mundy William R. , Thai Linda , Hudson Pearlie M. , Gallagher Michela , Tilson Hugh A. , Hong J. S. 
Published: May 2005

AbstractThe effects of aging on extracellular glutamate and tissue dynorphin content in the hippocampus were examined in Fischer‐344 rats. Young adult (4‐month‐old) and aged (24‐month‐old) rats were trained to find a hidden platform in the Morris water task. Aged rats were unable to acquire the spatial learning task as rapidly as young controls. Following behavioral testing, an in vivo microdialysis perfusion method was used to determine extracellular glutamate levels in the hippocampus. There was a 25–35% reduction in extracellular glutamate concentration in both dorsal and ventral hippocampus of aged rats compared to young rats, in the absence of any change in tissue glutamate levels. Radioimmunoassay showed an increase in dynorphin A(1–8)‐like immunoreactivity [DYN‐A(1–8)LI] in both dorsal and ventral hippocampus, but not striatum, of aged rats. Immunocytochemistry indicated that this increase was localized to the dentate granule cells and mossy fibers. Furthermore, among the aged rats the increase in DYN‐A(1–8)LI was inversely correlated with the decrease in extracellular glutamate. These results suggest that the disregulation of dynorphin observed in cognitively impaired aged rats is related to reduced excitatory transmission within the hippocampal formation.
The role of the perforant pathway as a trophic factor for neurotransmission in the rat dentate gyrus
Authors: Bekenstein Jonathan W. , Lothman Eric W. 
Published: May 2005

AbstractChanges in electrophysiological function in the hilar associational pathway terminating on dentate granule cells in the rat hippocampal formation were studied following unilateral entorhinal cortex lesions. In rats lesioned as pups (postnatal day 4 [PN 4]) or as adults (PN 60) there was a profound loss of paired‐pulse inhibition at 30 days postlesion. Inhibition was unaffected at 10 days postlesion. Entorhinal cortex lesions did not affect population spike amplitude, population excitatory postsynaptic potentials slopes, or long‐term potentiation compared to the unlesioned hemisphere. The presence of a complete hippocampal commissurotomy had no effect on excitatory or inhibitory parameters. Laminar analyses of extracellular field potentials from animals lesioned as adults revealed an expansion of functional synapses outward into the dentate molecular layer. This expansion was complete by 10 postlesion days. The changes observed with laminar analyses were not contemporaneous with the changes in paired‐pulse inhibition. The loss of inhibition in the hilar associational pathway of entorhinal cortex‐lesioned animals thus implies a change in local circuit function rather than an effect from sprouted associational fibers directly onto granule cells. The lack of inhibition in the associational pathway in lesioned animals was not due to a failure of local circuit inhibitory function to develop, since the same findings were obtained when lesions were made neonatally or as adults. Rather, the authors suggest that the present findings arise because of the formation of functional, recurrent, excitatory mossy fiber collateral synapses following entorhinal cortex lesions.
Comparison of the effects of ethanol and chlordiazepoxide on electrophysiological activity in the fascia dentata and hippocampus regio superior
Authors: Steffensen Scott C. , Henriksen Steven J. 
Published: May 2005

AbstractAcute intoxicating doses of ethanol‐producing blood alcohol levels of 120–200 mg% increase paired‐pulse (PP) inhibition in the dentate gyrus of anesthetized rats suggesting that ethanol increases recurrent inhibitory processes (Wiesner, J. B., and S. J. Henriksen (1987) Ethanol enhances recurrent inhibition in the dentate gyrus of the hippocampus. Neurosci. Lett. 79:169–173). To further understanding of the neuronal mechanisms underlying this phenomenon, the authors studied the effects of the benzodiazepine (BZ), chlordiazepoxide, and acute intoxicating levels of ethanol on extracellular field potential recordings and single‐unit activity in the dentate gyrus and area CA1 of the hippocampus. In the dentate, ethanol had no effect on population excitatory postsynaptic potential (pEPSP) amplitudes or slopes; decreased population spike (PS) amplitudes (25%); increased PP inhibition; decreased dentate granule cell (DGC) spontaneous activity (58%); had no effect on putative interneuron spontaneous activity; and markedly increased post field potential‐evoked interneuron discharges (IDs, 218%). Chlordiazepoxide had no effect on pEPSP amplitudes or slopes or PS amplitudes; increased PP inhibition; decreased DGC (62%) and interneuron (72%) spontaneous activity; and markedly decreased IDs (89%). In CA1, ethanol had no effect on pEPSP amplitudes or slopes; decreased PS amplitudes (26%); had no effect on PP responses; decreased pyramidal cell (PC) spontaneous activity (39%); had no effect on interneuron spontaneous activity; and markedly increased IDs (97%). Chlordiazepoxide had no effect on pEPSP amplitudes or slopes or PS amplitudes; had no effect on PP responses; decreased PC spontaneous activity (41%); and had no effect on interneuron spontaneous activity or IDs. The results suggest that the BZs decrease principal cell excitability by postsynaptic facilitation of inhibitory processes, whereas ethanol decreases principal cell excitability by postsynaptic facilitation of inhibitory processes, whereas ethanol decreases principal cell excitability indirectly by increasing the excitability of inhibitory interneurons.
Modulation of high‐threshold Ca current and spontaneous postsynaptic transient currents by phorbol 12, 13‐diacetate, 1‐(5‐isoquinolinesulfonyl)‐2‐methyl piperazine (H‐7), and monosialoganglioside (GM1) in CA1 pyramidal neurons of rat hippocampus in vitro
Authors: Agopyan N. , Miu P. , Krnjević K. 
Published: May 2005

AbstractPhorbol esters, which activate protein kinase C (PKC), enhance synaptic transmission in the CA1 subfield of hippocampus, both in situ and in vitro. The increase in synaptic transmission could be the consequence of enhanced Ca influx into nerve terminals, and perhaps a more general increase in voltage‐dependent Ca currents. The effects of phorbol 12, 13‐diacetate (PDAc) on the high‐voltage activated (HVA) Ca currents, as well as spontaneous transient currents were therefore investigated by intracellular recording in hippocampal slices. PDAc selectively augmented, by 45% ± 10%, the early peak of the HVA Ca current (but not its sustained component), and also spontaneous inhibitory postsynaptic currents. The inactive phorbol ester, 4 α‐PDAc, had no comparable effects. The actions of PDAc were reversible on prolonged washing, and they were antagonized by the PKC inhibitors (1‐(5‐isoquinolinesulfonyl)‐2‐methyl) piperazine (H‐7) and monosialoganglioside (GM1). In addition, GM1, which also activates the Ca/calmodulin‐dependent kinase, enhanced spontaneous excitatory postsynaptic currents, while inhibiting the IPSCs. It is concluded that activation of PKC increases HVA (probably N‐type) Ca current and facilitates ongoing GABAergic IPSCs.
Accumulation of glutamate is regulated by calcium and protein kinase C in rat hippocampal slices exposed to ischemic states
Authors: Lu Y. Ming , Lu B. Feng , Zhao F. Qing , Yan Y. Lan , Ho X. Pin 
Published: May 2005

AbstractThere is now convincing evidence that excessive accumulation of the excitatory amino acid glutamate (Glu) in the extracellular space is toxic to neurons. However, the regulation of the release and uptake of Glu in producing this toxic concentration has not been adequately ascertained. The authors report that in hippocampal slices, the output of Glu significantly increased under in vitro ischemic states. Glu in the extracellular space increased fivefold. Since daurisoline, a drug that blocks N‐type Ca2+ channels, or Ca2+ ‐free solution potently and effectively lowered this stimulated output, it was hypothesized that the Glu output is mediated by Ca2+ influx in nerve terminals. When the slices were incubated for 30 minutes under ischemic state, daurisoline caused only small alterations in the postischemic accumulation of Glu. However, Glu accumulation was markedly attenuated by H‐7, but not by calmidazolium, facilitated by PDB whereas 8‐bromo‐cAMP was without effect. It appears therefore that during a 30‐minute ischemic insult, protein kinase C (PKC) was involved in the Glu accumulation of supernatant. A direct demonstration of this concept was obtained by showing significant increases in PKC activation in presynaptic nerve terminals (from 1.34 ± 0.1 to 9.34 ± 0.89 U) following 30 minutes of ischemia. DNQX, a non‐NMDA receptor antagonist, potently reduced PKC activities and decreased extra Glu accumulation. Also observed was the inhibition of 1‐[3H]‐Glu uptake into synaptosomes by PDB. These results provide direct evidence that Ca2+ influx enhances Glu release, which in turn leads to inhibition of its reuptake, and is coupled with PKC activities in presynaptic nerve terminals.
Perineuronal satellitosis in the human hippocampal formation
Authors: Vijayan Vijaya K. , Zhou Shan‐Shan , Russell Michael J. , Geddes Jim , Ellis William , Cotman Carl W. 
Published: May 2005

AbstractA previously unreported example of perineuronal satellitosis in the medial CA1 and adjacent subiculum in the human hippocampal formation is described. This phenomenon is characterized by a clustering of glial cells in relation to the perikarya of a subpopulation of neurons in the deep pyramidal layer and around most neurons scattered in the stratum oriens and subcortical white matter. Most of the perineuronal satellite glia were identified as oligodendrocytes based on their nuclear chromatin patterns and antigenic properties. Satellite oligodendrocytes were mostly of the medium dense variety. A type of satellite glia with nuclear features of the dark oligodendrocyte could not be identified unequivocally using the antigenic criteria employed in this study.
Hippocampal function in the rat: Cognitive mapping or vicarious trial and error?
Authors: Amsel Abram 
Published: May 2005

AbstractThe most prominent hypothesis of hippocampal function likens the hippocampus to a “cognitive map,” a term used by a famous learning theorist, E. C. Tolman, to explain maze learning. The usual application of this concept of cognitive map, as it applies to the hippocampus, is to what is called spatial learning, mainly in the radial‐arm maze of Olton and the Morris water maze. In a recent Hippocampus Forum, evidence for the cognitive map hypothesis was reviewed in a lead article by Nadel, followed by a series of commentaries by leading investigators of hippocampal function. This speculative commentary offers an alternative not represented in the forum—that the function of the hippocampus in spatial learning is not as a cognitive map, but that it subserves another function proposed by Tolman in his work on simple discrimination learning, vicarious trial and error, based on incipient, conflicting dispositions to approach and avoid.
Autoradiographic comparison of cholinergic and other transmitter receptors in the normal human hippocampus
Authors: Perry Elaine K. , Court Jennifer A. , Johnson Mary , Smith Carthage J. , James Victoria , Cheng Anthony V. , Kerwin Janet M. , Morris Christopher M. , Piggott Margaret A. , Edwardson James A. , Birdsall Nigel J. M. , Turner Jonathon T. , Perry Robert H. 
Published: May 2005

AbstractThe vulnerability of the human hippocampal complex to disease, trauma, and aging indicates the necessity to target this area therapeutically. The distribution and density of transmitter receptors provide a rational basis for this approach, and in this study the topography of 11 different pharmacological sites is compared with the cholinergic innervation, which is partcularly vulnerable in dementia. The regional distribution of cholinergic innervation to the normal adult human hippocampus and adjacent cortex, marked by acetylcholinesterase (AChE) fiber and terminal reactivity, is notable for its concentration in CA2/3 of Ammon's horn and the dentate fascia. Neither nicotinic (high‐affinity nicotine binding) nor muscarinic (“M1” or “M2”) cholinergic receptor binding paralleled this distribution. In Ammon's horn, 5‐HT2 and kainate receptor binding more closely resembled the pattern of AChE, being concentrated in CA2–4 compared with CA1. By contrast, muscarinic M1 and M2, 5‐HT1A, benzodiazepine (including zolpidem‐insensitive binding), NMDA (MK801), and AMPA/QUIS receptors were higher in CA1 and/or subiculum. Kainate binding, like AChE, was high in CA4. 5‐HT2 and nicotinic binding partially mimicked the pattern of AChE around the granule layer. In the subicular complex and parahippocampal gyrus, where cholinergic activity is relatively lower, muscarinic, 5‐HT1A, and benzodiazepine binding were relatively high and the nicotinic receptor was remarkable for its highest density compared to other areas examined. In stratum lacunosum‐moleculare of CA1, which was relatively low in AChE activity, there was a dense band of nicotinic, M2, and benzodiazepine receptor binding. These observations, while reflecting the anatomical complexity of chemical signaling in the hippocampal region, indicate a unique distribution for the nicotinic receptor and suggest that the cholinergic input may specifically interact with 5‐HT and excitatory amino acid systems via 5‐HT2 and kainate receptor subtypes in governing signaling to the dentate and CA3 regions.
Induction of glial fibrillary acidic protein immunoreactivity in the rat dentate gyrus after adrenalectomy: Comparison with neurodegenerative changes using silver impregnation
Authors: Krugers Harm J. , Medema Rikje M. , Postema Folkert , Korf Jakob 
Published: May 2005

AbstractIn the present study we performed a light microscopic anatomical comparison of adrenalectomy (ADX)‐induced neurodegeneration using silver impregnation and reaction of astroglial cells using GFAP immunocytochemistry in the hippocampus of the rat. Three survival times following ADX were studied: 24 hours, 3 days, and 3 weeks. Twenty‐four hours following ADX we found no degenerative changes or altered GFAP immunostaining. Three days after adrenalectomy, argyrophilic somata appeared in the granular cell layer of the dentate gyrus. Argyrophilic dendrites were seen in the molecular layer of the dentate gyrus and neuritic argyrophilia were seen in the mossy fiber layer. Induction of GFAP immunoreactivity occurred simultaneously with degeneration. Increased GFAP immunoreactivity could be observed 3 days after adrenalectomy in the molecular layer of the dentate gyrus, granular cell layer, sub and supragranular cell layer, and mossy fiber layer. Size and shape of astroglial cells were changed, and their processes in the molecular layer changed from unidirectional to randomly organized. Degeneration and astroglial reaction were more pronounced 3 weeks after adrenalectomy and both were prevented by adding corticosterone to the drinking solution. Animals that did not show degenerative changes showed no increased GFAP immunoreactivity, while both effects were confined to the dentate gyrus and mossy fiber zone. These results show that there is a close relationship between the induction of GFAP immunoreactivity in the hippocampus of the rat and neuronal degeneration in the dentate gyrus following ADX, both in time and space. © 1994 Wiley‐Liss, Inc.
Potassium‐induced long‐term potentiation in area CA1 of the hippocampus involves phospholipase activation
Authors: Bernard Julie , Lahsaini Ahmed , Massicotte Guy 
Published: May 2005

AbstractPrevious studies have shown that potassium‐induced long‐term potentiation (LTP) of the Schaffer collateral/commissural synapses in area CA1 of the hippocampus shares common properties with tetanus‐induced LTP. In the present investigation, we performed electrophysiological and binding experiments on CA1 hippocampal slices to evaluate the location and nature of the changes underlying potassium‐induced LTP. Paired‐pulse facilitation, which represents an index of transmitter release, was markedly reduced by potassium‐induced LTP. In addition, KC1‐induced LTP was associated with an increase in 3H‐AMPA ([3H]‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate) binding to CA1 synaptic membranes when measured 40 min after high‐potassium exposure; however, no changes were detected in binding of an antagonist ([3H]‐6‐cyano‐7‐nitroquinoxaline‐2,3‐dione; 3H‐CNQX) to AMPA receptors in slices expressing KC1‐induced LTP. Administration of the phospholipase A2 (PLA2) inhibitor bromophenacyl bromide (BPB) prior to potassium application prevented LTP formation as well as the changes in paired‐pulse facilitation and 3H‐AMPA binding that characterized this type of potentiation. Taken together, these data indicate that potassium‐in‐duced LTP may be related to modifications in both pre‐and postsynaptic properties and confirm the hypothesis that PLA2 activation is an important mechanism in long‐term changes of synaptic operation. © 1994 Wiley‐Liss, Inc.
Genetic and activity‐dependent regulation of Zif268 expression: Association with spatial learning
Authors: Fordyce Diana E. , Bhat Ratan V. , Baraban Jay M. , Wehner Jeanne M. 
Published: May 2005

AbstractWe have reported that C57BL/6 and DBA/2 mice differ in spatial learning performance and associated hippocampal protein kinase C (PKC) activity (Upchurch and Wehner, 1989, Behav Neurosci 103:1251–1258; Wehner et al., 1990, Brain Res 523:181–187) and that physical activity enhances spatial learning with related alterations in protein kinase C (PKC) (Fordyee and Wehner, 1993b, Brain Res 619:111–119). To assess whether physical activity induces alterations in gene expression that may underlie these changes in PKC and learning performance, we examined the effect of physical activity on expression of zif268, a transcription regulatory factor linked to stimulus‐induced neuronal plasticity. C57 and DBA mice, 3 months of age, were subjected to acute (one bout) or chronic (8 weeks) physical activity. The mice were then tested on the Morris water maze task for 6 days with subsequent analysis of PKC activity and zif268 mRNA expression. Control DBA mice, which have poor hippocampal‐specific learning performance compared to C57 mice (Wehner et al., 1990, Brain Res 523:181–187; Fordyce and Wehner, 1993b, Brain Res 619:111–119; Paylor et al., 1993, Psychobiology 27:11–26), displayed lower basal levels of zif268 mRNA (P <.05). As observed previously, chronic physical activity produced an enhancement in spatial learning performance accompanied by alterations in hippocampal PKC activity in both strains of mice (P <.05). In addition, the present investigation demonstrated that acute physical increased mRNA levels of zif268 in hippocampal regions CA1, CA3 and overlying cortex (P <.005) of both C57 and DBA mice. Chronic physical activity suppressed the basal expression of zif268 in C57 mice in CA1 and overlying cortex below control levels. These findings suggest that genetic and activity‐dependent regulation of zif268 may influence learning performance. © 1994 Wiley‐Liss, Inc.