摘要:

AbstractWe investigated the functional and behavioral implications of chronic corticosteroid removal in young and middle‐aged rats. Prepubertal and 13‐month‐old rats were adrenalectomized (ADX) or sham operated (SHAM). The young ADX rats were divided further into three groups: ADX with no hormone replacement, ADX given corticosterone chronically, (chCORT), and ADX given corticosterone acutely at the time of Morris water maze testing (acCORT). All rats were run on the Morris water maze 12 weeks after surgery. They were then sacrificed and the brains were removed for histological analysis.The results showed that prolonged corticosteroid absence caused major damage to the dentate gyrus and learning impairment on the Morris water maze. The chCORT rats had little dentate gyrus cell loss and were as efficient as the controls in Morris water maze performance, whereas the acCORT rats had dentate gyrus cell loss and were impaired in the spatial acquisition task. Furthermore, exogenously administered corticosterone had an interactive effect on ADX rats. Water maze performance was improved in dentate gyrus damaged rats (acCORT) compared to ADX rats not given corticosterone, whereas ADX rats with very little dentate gyrus damage (chCORT) did not exhibit better water maze performance relative to controls. Middle‐aged ADX rats lost cells only in the dorsal blade of the dentate gyrus but they did not show a learning impairment in the Morris water maze relative to the middle‐aged controls. These results indicate that corticosteroids are trophic for the dentate gyrus, that mature granule cells are less affected by adrenalectomy, that corticosteroid absence is responsible for some water maze impairment in ADX rats, but that in addition to corticosteroid absence, a substantial amount of dentate gyrus damage is necessary to impair spatial learning. © 1995 Wiley

ISSN:1050-9631    

DOI:10.1002/hipo.450050103

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractRats were trained in a water maze in a dark room with the extramaze cues restricted to only dimly back‐lit shapes. We used lidocaine to reversibly lesion the dorsal hippocampus and this controlledcue room in order to examine interhippocampal synthesis of lateralized place engrams. Experiment 1 showed that lidocaine injected into both hippocampi effectively abolished place navigation for up to 25 min but not at 45 min. In experiment 2, each day under lidocaine blockade of one hippocampus, pretrained rats were trained in the water maze to locate the target according to two cues (e. g., AB). Two hours later, the contralateral hippocampus was inactivated and the rats were trained to the same location with two other cues (CD). On day 5, intact brain retrieval was tested in one of three conditions: ACQ (e. g., AB), one of the pairs of cues used in acquisition training; SYNTH (e. g., AC), one cue from each of the pairs used in acquisition; CONT (e. g., AE), one cue that was used in acquisition training and a novel cue. The results show that the hippocampi learned the two tasks independently and similarly [latency (L) at the asymptote = 7 s]. Retrieval performance was at the asymptote for ACQ (AB) and SYNTH (AC) (L = 6 and 7, respectively) but was disrupted for CONT (L = 12). In experiment 3 as in experiment 2, the rats were trained, under unilateral blockade, to a new place for 4 days. On day 5, retrieval with the trained hippocampus blocked was worse (L = 11) than with the untrained side blocked (L = 5). We conclude that interhippocampal synthesis of lateralized place engrams is automatic and highly efficient. © 1995 Wiley‐Liss,

ISSN:1050-9631    

DOI:10.1002/hipo.450050104

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractImmunohistochemical staining for the calcium‐binding protein calbindin‐D28k(CaBP) was combined with Lucifer Yellow (LY) identification and intracellular recording of changes in membrane parameters of pyramidal neurons in CA2, CA1, and the sebiculum of rat hippocampal slices during brief exposure (4.0 ± 0.19 min) to N2. Anoxia evoked either a depolarization or hyperpolarization of membrane potential (VM) (+21.5 ± 2.79 mV above VM= −70.5 ± 1.50 mV, n = 30 and −7.2 ± 0.72 mV below VM= −68.2 ± 1.34 mV, n = 24, respectively) and a fall in membrane resistance of =20%. Differences in the response could be correlated with the presence or absence of CaBP and the localization of neurons in different layers of stratum pyramidale and sectors of the hippocampus. For neurons immunopositive for calbindin (CaBP(+)), depolarization was observed more frequently (83%) than hyperpolarization (17%); in contrast, 44% of responses of calbindin‐negative (CaBP(−)) neurons were depolarizing and 56% were hyperpolarizing. Depolarizations of CaBP(+) neurons were more gradual in slope, and more rapidly reached a plateau in comparison with those recorded in CaBP(−) neurons. Responses of neurons in the superficial layer of stratum pyramidale (in which 79% of CaBP(+) pyramidal neurons were situated) were mainly depolarizing (91%), while for those in the deep layer (which contained 89% of the CaBP(−) cells) such responses were observed less often (45%). Depolarization was also more common than hyperpolarization for cells located in CA2/CA1c/CA1b (63%) than in the CA1a/subicular region (37%). The depolarizing response of the majority of pyramidal neurons which are CaBP(+), superficial, and closer to CA3 may reflect an efficient buffering of intracellular Ca2+, which maintains a low [Ca2+]i, steep gradient for Ca2+influx and may facilitate the movement of Ca2+away from points of entry. The neurons which are CaBP(−), deep, and closer to subiculum and in which N2evokes hyperpolarization, on the other hand, may have a sustained elevation/accumulation of cytosolic Ca2+which could activate K+conductance, inhibit Ca2+influx, and stabilize the membrane potential. These experiments provide a functional correlate for CaBP and suggest that it may have a significant role in Ca2+homeostasis and the determination of selective neuronal vulnerability

ISSN:1050-9631    

DOI:10.1002/hipo.450050105

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractThe present study was designed to determine if and to what extent somatostatin (SST) synthesizing neurons of the hippocampal formation are activated during seizures, elicited through kindling of the perforant pathway. Tissue was used and analyzed from animals which had experienced a single afterdischarge, or a stage 3 or stage 5 seizure. The protein expression of the oncogene c‐fos in activated, depolarizing neurons was utilized to identify seizure‐activated SST‐synthesizing neurons. Combined immunocytochemical and in situ hybridization methods were used to identify these double‐labeled, Fos protein, and SST mRNA‐containing neurons. The results were quantified and compared across seizure stages. The resulting data demonstrate that at every stage of seizure development, a majority of SST‐synthesizing neurons is activated, but that these activated SST mRNA‐containing neurons represent only a minority of all seizure‐activated, Fos‐expressing neurons in the hippocampal formation. The data further reveal a numerical hierarchy in which the majority of double‐labeled neurons is present in the hilus of the dentate, followed by the stratum oriens of CA1. It is concluded that SST‐synthesizing neurons represent an integral component of the kindling activated neuronal network and, since the SST synthesizing neurons represent the minority of all seizure‐activated neurons in the hippocampal formation, that this neuronal network is likely to be of considerable neurochemical complexit

ISSN:1050-9631    

DOI:10.1002/hipo.450050106

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractActivation of the lateral perforant path input to the dentate gyrus with theta‐patterned conditioning trains produced LTP of synaptic efficacy that changed in magnitude as an inverted U‐shaped function of the number of trains. The LTP induction function was not fixed, however, and could be shifted to the left by administering 5 Hz “priming” stimulation to the lateral path 10 min prior to the conditioning trains. The priming effect was input specific and selective to a narrow window of stimulus frequencies. The shift to the left of the LTP induction function by priming stimulation was blocked by the muscarinic receptor antagonist atropine sulphate. Nimodipine, an antagonist of L‐type voltage‐sensitive calcium channels, did not mimic the priming effect but instead produced a general facilitation of LTP is induction. These data demonstrate that the degree to which LTP is induced in the lateral path is a non‐linear function of afferent activity, and that this function, including LTP threshold, can be shifted to the left by prior synaptic activity at hippocampal theta‐rhythm frequencies. © 1995

ISSN:1050-9631    

DOI:10.1002/hipo.450050107

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractWe analyzed the distribution and light‐microscopic features of the NADPH diaphorase‐containing structures in the lizard hippocampus, likely to correspond to nitric oxide. We also studied co‐localization of NADPH diaphorase with the neurotransmitter GABA, the calcium‐binding protein parvalbumin, and the neuropeptide somatostatin, in order to examine whether putative nitric oxide‐synthesizing neurons represent a different subpopulation of GABA cells, on which the authors recently reported in lizards. We also studied co‐localization of NADPH diaphorase with parvalbumin or somatostatin in mice to ascertain whether the characteristics of this population in reptiles parallel the situation in mammals. Most of the positive NADPH diaphorase neurons were stained in a Golgi‐like manner and were in the plexiform layers of the lizard hippocampus with morphologies ranging from bipolar to multipolar. Co‐localization with GABA was 100%, and NADPH diaphorase‐positive neurons in the lizard hippocampus did not contain parvalbumin or somatostatin. The results indicate that putative nitric oxide‐synthesizing neurons represent a distinct subpopulation of GABA interneurons in the lizard hippocampus. Two different types of fibers were described in the plexiform layers: one type bearing thick varicosities, and the other thinner ones. We discuss the possibility that at least part of the positive fibers arise from a hypothalamic aminergic nucleus containing the third ventricle, the periventricular hypothalamic organ. Most radial glia were stained almost completely and formed typical end‐feet both at the pia and around capillaries. The results of this study confirm that the capacity for synthesizing nitric oxide is linked to a determined set of neuronal markers depending on the specific brain region, and they provide new resemblances between hippocampal regions in different classes of vertebrates.

ISSN:1050-9631    

DOI:10.1002/hipo.450050108

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractHow adenosine leakage and tetanic release might affect long‐term potentiation (LTP) was investigated by applying adenosine antagonists 8(p‐sulfophenyl)theophylline (8SPT) or 8‐cyclopentyl‐3, 7‐dihydro‐1, 3‐dipropyl‐1H‐purine‐2, 6‐dione (DPCPX) to slices, while recording CA1 field EPSPs and population spikes. In the first series of experiments, we applied weak double tetani (at 100 Hz, for 1 s) that were subliminal for evoking LTP in initial control runs. In the presence of 8SPT—at concentrations (10–50 μM) which block both A1and A2receptors—the same tetani consistently evoked LTP of population spikes butnotof excitatory postsynaptic potentials (EPSPs), whereas DPCPX (50 nM), which blocks only A1receptors, facilitated LTP of both EPSPs and population spikes. These results are consistent with previous evidence that tetanic adenosine release on the one hand depresses LTP via A1receptors but on the other facilitates LTP via A2receptors.In a second set of experiments, 8SPT (50–100 μM) did not prevent the induction of LTP of both EPSPs and population spikes by stronger tetanic stimulation. Therefore A2receptor activation is not essential for the induction of LTP when stronger tetani are applied. Overall, the main effect of endogenous adenosine release is to oppose LTP in

ISSN:1050-9631    

DOI:10.1002/hipo.450050109

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractThe cellular‐synaptic generation of rhythmic slow activity (RSA or theta) in the hippocampus has been investigated by intracellular recording from principal cells and basket cells in anesthetized rats. In addition, the voltage‐, coherence‐, and phase versus depth profiles were examined by simultaneously recording field activity at 16 sites in the intact rat, during urethane anesthesia, and after bilateral entorhinal cortex lesion. In the extracellular experiments the large peak of theta at the hippocampal fissure was attenuated by urethane anesthesia and abolished by entorhinal cortex lesion. The phase versus depth profiles were similar during urethane anesthesia and following entorhinal cortex lesion but distinctly different in the intact, awake rat. These observations suggest that dendritic currents underlying theta in the awake rat may not be revealed under urethane anesthesia.The frequency of theta‐related membrane potential oscillation was voltage‐independent in pyramidal neurons, granule cells, and basket cells. On the other hand, the phase and amplitude of intracellular theta were voltage‐dependent in all three cell types with an almost complete phase reversal at chloride equilibrium potential in pyramidal cells and basket cells. At strong depolarization levels (less than 30 mV) pyramidal cells emitted calcium spike oscillations, phase‐locked to theta. Basket cells possessed the most regular membrane oscillations of the three cell types. All neurons of this study were verified by intracellular injection of biocytin. The observations provide direct evidence that theta‐related rhythmic hyperpolarization of principal cells is brought about by the rhythmically discharging basket neurons. Furthermore, the finding that basket cells were also paced by rhythmic inhibitory postsynaptic potentials during theta suggest that they were periodically hyperpolarized by their GABAergic septal afferents.&1995

ISSN:1050-9631    

DOI:10.1002/hipo.450050110

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractA large body of evidence exists to demonstrate that excitatory amino acids (EAA) and their receptors are involved in the pathophysiological mechanisms linking several acute brain insults, such as cerebral ischemia, to neuronal degeneration and death. Accordingly, the use of EAA receptor antagonists can be beneficial in attenuating or preventing the neuronal irreversible damage subsequent to various neuropathological syndromes. We have investigated the effect of 15 min of simulated ischemic conditions, i. e., oxygen/glucose deprivation, on hippocampal slices preparation measuring, as neurotoxicity indexes, both the amino acids efflux in the incubation medium, detected by HPLC, and the inhibition of protein synthesis, evaluated as3H‐Leucine incorporation into proteins. Accumulation of neurotransmitter amino acids was measured in the medium during the “ischemic” period. Glutamate increased 30‐fold over the basal level while aspartate was sevenfold and GABA 12‐fold higher than in normal conditions. After a reoxygenation period of 30 min, the rate of protein synthesis of hippocampal slices subjected to “ischemia” was reduced to 35–50% of controls. The non‐competitive NMDA antagonist MK‐801 (100 μM) and the competitive NMDA antagonist CGP 39551 (100–250 μM) as well as the non‐NMDA receptor antagonist NBQX (100 μM) and AP3 (300 μM) were unable to counteract the metabolic impairment when they were present alone in the incubation fluid during simulated “ischemia.” An incomplete, but highly significant (p<0.001), protection from protein synthesis impairment was achieved in the presence of an equimolar concentration (100 μM) of MK‐801 and NBQX. A similar protective effect could be reproduced using 100 μM NBQX in concomitance with a high Mg++(20 μM) voltage‐dependent block of the NMDA receptor‐associated channel but not exposing the slices to a NBQX (100 μM) and CGP 39551 (100–250 μM) mixture. The recovery of protein synthesis in the presence of the MK‐801/NBQX effective combination was not paralleled by a detectable decrease in the amount of amino acids released in the incubation medium during the “ischemic” period. Taken together, the present data allow new insights into neurotoxicity‐mediating mechanisms, suggesting that multiple additive processes are involved and that antagonists acting at different sites on excitatory amino acid receptor subtype can show diffe

ISSN:1050-9631    

DOI:10.1002/hipo.450050111

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

ISSN:1050-9631    

DOI:10.1002/hipo.450050102

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY