摘要:

AbstractIn this study we describe a model of connectivity linking the different neurons in the CA3 and CA1 areas of the young male rat hippocampus. The anatomical and electrophysiological values of the parameters used in the model were selected from the available literature. Each type of synapse was characterized by its spatial location on the dendritic tree, its weight, its probability of activation, and the ionotropic receptors involved. We have shown that the degree of convergence and divergence of inputs is highly dependent upon the type of neuron and its spatial location. The different gradients of connectivity we describe support the lamellar hypothesis from a functional point of view, even if the anatomical patterns seem diffuse. The analysis of the proportion of common afferents to a class of neurons further confirmed this point. It is suggested that the circuitry creates local coherence in terms of processing of information by establishing restricted areas where information is preferentially treated. The functional consequences and limitations of these findings are also discussed. This model is the first step in the development of a network model of the hippocampus with realistic architecture. © 1994 Wiley‐Liss, I

ISSN:1050-9631    

DOI:10.1002/hipo.450040502

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

年代:1994

数据来源: WILEY

摘要:

AbstractThe mRNAs for two forms of glutamic acid decarboxylase (GAD65 and GAD67) were localized in the rat hippocampal formation by nonradioactive in situ hybridization methods with digoxigeninlabeled cRNA probes. Some neurons in all layers of the hippocampus and dentate gyrus were readily labeled for each GAD mRNA, and the patterns of labeling for GAD65 and GAD67 mRNAs were very similar. All major groups of previously described GAD‐and GABA‐containing neurons appeared to be labeled for each GAD mRNA. Such findings suggest that most GABA neurons in the hippocampal formation contain both GAD mRNAs. When the labeling of neurons in the hippocampal formation and cerebral cortex was compared in the same sections, the intensity of neuronal labeling for GAD67 mRNA was generally similar in the two regions. However, the intensity of labeling for GAD65 mRNA was generally stronger for many neurons in the hippocampal formation than for most neurons in the cerebral cortex. Neurons in the hilus of the dentate gyrus were particularly well labeled for GAD65.The nonradioactive labeling for the GAD mRNAs was confined to the cytoplasm of neuronal cell bodies, and this allowed a clear visualization of the relative number and location of labeled neurons. Several distinct patterns of GAD mRNA‐containing neurons were observed among different regions of the hippocampal formation. In the hilus of the dentate gyrus, GAD mRNA‐containing neurons were numerous in the regions deep to the granule cell layer as well as in more central parts of the hilus. Within CA3, the densities (quantities) of labeled neurons varied among the regions. In the inner or hilar segment of CA3, the density of labeled neurons was often lower than that in the outer part of CA3 where numerous labeled neurons were distributed throughout all layers. In CA1, GAD mRNA‐labeled neurons were distributed in a relatively laminar pattern with the highest density in stratum pyramidale and moderate densities in stratum oriens and at the interface between strata radiatum and lacunosum‐moleculare. Lower densities were found within the latter two layers.The prominent localization of the two GAD mRNAs in the hippocampal formation suggests that dual system for GABA synthesis is necessary for normal GABAergic function in this brain region. Most putative GABA neurons contain relatively high levels of GAD67 mRNA as might be expected if this GAD form is responsible for the synthesis of GABA for metabolic and baseline synaptic function. The relatively high levels of GAD65 mRNA in many hippocampal neurons, particularly those of the dentate hilus, may indicate that these neurons have a well‐developed reserve system for GAD and GABA synthesis. © 1994 W

ISSN:1050-9631    

DOI:10.1002/hipo.450040503

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

年代:1994

数据来源: WILEY

摘要:

AbstractBathing hippocampal slices in the potassium channel blocker tetraethylammonium (TEA), while stimulating the Schafer collaterals at a low frequency, induces Ca2+‐dependent,N‐methyl‐D‐aspartate (NMDA) receptor‐independent long‐term potentiation of synaptic transmission (LTPk) in CA1 neurons. We have combined ratio imaging of fura‐2 and mag‐fura‐5 in hippocampal CA1 neurons with intracellular and field recordings to evaluate postsynaptic Ca2+changes that occur in the induction of LTPk. Test stimuli were applied at 0.05 Hz to stratum radiatum in the presence of the NMDA receptor antagonistsD,L‐2‐amino‐5‐phosphonovaleric acid (100μM) or MK‐801 (10μM). During TEA exposure (15–25 mM; 10 min), cells fired prolonged action potentials both spontaneously and in response to test stimuli resulting in transient, micromolar Ca2+accumulations in both somata and dendrites. The initial EPSP slope, measured 60 min after TEA wash‐out, was potentiated to approximately 200% of control. The Ca2+channel blocker nimodipine (10 μM) greatly reduced Ca2+transients in both magnitude and duration and prevented LTPkinduction. Pretreatment of slices with compounds that block metabotropic glutamate receptor (mGluR)‐stimulated phosphoinositide hydrolysis,L‐2‐amino‐3‐phosphonopropionic acid (L‐AP3, 50‐200 μM) orL‐aspartate‐β‐hydroxamate (50–100 μM), as well as protein kinase C (PKC) inhibitors (sphingosine, 20 μM; RO‐31‐8220, 0.2 μM; or calphostin C, 2 μM) also blocked LTPk. Ca2+transients were unaffected byL‐AP3 or RO‐31‐8220. These findings suggest that Ca2+influx through voltage‐gated channels and co‐activation of PKC by mGluRs are both necessary for induction of LTPk. Activation of mGluRs must also occur in NMDA receptor‐dependent induction paradigms, but is possibly of lesser importance owing to the much gr

ISSN:1050-9631    

DOI:10.1002/hipo.450040504

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

年代:1994

数据来源: WILEY

摘要:

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 ofzif268, 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 andzif268mRNA 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 ofzif268mRNA (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 ofzif268in hippocampal regions CA1, CA3 and overlying cortex (P<.005) of both C57 and DBA mice. Chronic physical activity suppressed the basal expression ofzif268in C57 mice in CA1 and overlying cortex below control levels. These findings suggest that genetic and activity‐dependent regulation ofzif268may influence learning performance. © 19

ISSN:1050-9631    

DOI:10.1002/hipo.450040505

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

年代:1994

数据来源: WILEY

摘要:

AbstractWe studied the ontogeny of inhibitory and excitatory processes in the rat dentate gyrus by examining paired‐pulse plasticity in the hippocampal slice preparation. The mature dentate gyrus produces characteristic paired‐pulse responses across a wide range of interpulse intervals (IPI). Paired‐pulse effects on population excitatory postsynaptic potential (EPSP) slope and population spike (PS) amplitude were analyzed at postnatal day 6 (PN6), PN7/8, PN9/10, PN15/16, and PN>60.The synaptic paired‐pulse profile (10–5,000 ms IPI) matured by PN7/8. The triphasic pattern of short‐latency depression, a relative facilitation at intermediate intervals, and long‐latency depression was present at all ages tested. Paired‐pulse effects on granule cell discharge indicated the presence of weak short‐latency (20 ms IPI) inhibition at PN6, the earliest day that a population spike could be evoked. By PN7/8, short‐latency inhibition was statistically equivalent to the mature dentate gyrus. Long‐latency (500–2,000 ms IPI) PS inhibition was present, and equal to the mature dentate gyrus by PN6. The most consistent difference between the mature and developing dentate gyrus occurred at intermediate IPIs (40–120 ms) where spike facilitation was significantly depressed in the developmental groups.The studies indicate that short‐term plasticity matures rapidly in the dentate gyrus and suggest that the inhibitory circuitry can function at a surprisingly early

ISSN:1050-9631    

DOI:10.1002/hipo.450040506

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

年代:1994

数据来源: WILEY

摘要:

AbstractRats with damage to the hippocampal formation and allied structures are hyperactive in many test situations but the cause of this hyperactivity is not known. Here the activity of control rats and rats with fimbria‐fornix lesions is documented in tests of overnight activity. Details of activity are then characterized from video recordings of behavior in an open field. Rats with fimbria‐fornix lesions make significantly more stops of shorter duration and thus more individual trips than control rats but they do not differ in the distance traveled on individual trips or in travel speed. It is suggested that the main difference between fimbria‐fornix rats and control rats is that when fimbria‐fornix rats stop they remain “still” for shorter durations than do control rats. This finding is discussed in relation to a theory of locomotor/exploratory behavior, and in relation to its implications with respect to the performance of fimbria‐fornix rats in studies of learning and memory. © 1994 W

ISSN:1050-9631    

DOI:10.1002/hipo.450040507

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

年代:1994

数据来源: WILEY

摘要:

AbstractThe number of orthodromically evoked population spikes was used to classify brain slice tissue from the dentate gyrus of temporal lobe epileptic patients as “more excitable” (multiple population spikes) or “less excitable” (a single population spike). During orthodromic stimulation, “more excitable” tissue exhibited less paired‐pulse depression in comparison to “less excitable” tissue. During antidromic stimulaltion, both multiple population spikes and paired‐pulse depression were observed in “more excitable” tissue. “Less excitable” tissue exhibited a single antidromic spike and often on antidromically evoked paired‐pulse depression. The strength of antidromic paired‐pulse depression was correlated positively with the number of antidromic spikes and was correlated negatively with orthodromic paired‐pulse depression. Although orthodromic and antidromic paired‐pulse depression were correlated to the number of orthodromically evoked populaltion spikes, this correlation was not as strong as that between orthodromic paired‐pulse depression, antidromic paired‐pulse depression, and number of antidromically evoked population spikes.The antidromic paired‐pulse depression observed in tissue exhibiting antidromically evoked multiple population spikes was enhanced rather than blocked by bicuculline. In addition, the blockade of the antidromic paired‐pulse depression by CNQX indicated that this inhibition is mediated by an AMPA‐type glutamatergic synapse. We suggest that alterations in circuitry occur in the dentate gyrus of some temporal lobe epileptic patients and were manifested by both a loss of inhibitory input as well as an increase of inhibition, which was dependent on the pathway of stimulaltion. The results of pairing antidromic and orthodromic stimuli were consistent w

ISSN:1050-9631    

DOI:10.1002/hipo.450040508

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

年代:1994

数据来源: WILEY

摘要:

AbstractThe goal of the present study was to identify and characterize, at the electron microscopic level, the synapses formed by entorhinal cortical (EC) axons in the hippocampal CA1 stratum lacunosummoleculare of the adult rat.Phaseolus vulgarisleucoagglutinin was ionotophoresed at various loci throughout the mediolateral and dorsoventral extent of the EC to label EC‐CA1 synapses. Virtually all labeled synapses were asymmetric and axospinous. EC axons did not preferentially synapse with any particular type of dendritic spine; rather, EC axons formed synapses with the range of dendritic spine morphologies observed in CA1 s. lacunosum‐moleculare. Spines with either perforated or nonperforated postsynaptic densities were contacted by EC axons. Occasionally both a labeled and an unlabeled axon synapsed on a single dendritic spine head. The data are discussed in relation to the morphology of other afferent systems synapsing in s. lacunosum‐moleculare and to the physiology of the EC‐CA1 system. © 1994 Wiley

ISSN:1050-9631    

DOI:10.1002/hipo.450040509

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

年代:1994

数据来源: WILEY

摘要:

AbstractVarious paradigms have been used to assess the capacity of the adult brain to undergo activity‐dependent morphological plasticity. In this report we have employed recurrent limbic seizures as a means of studying the effects of this form of enhanced neuronal activity on cellular morphology and, in particular, on the incidence of somatic spines on the dentate gyrus granule cells. Seizure activity was induced by the placement of focal, unilateral electrolytic lesions in the dentate gyrus hilus of adult rats. At various intervals postlesion, rats with behaviorally verified seizures were sacrificed, and the hippocampicontralateral, to the lesions were removed and prepared for electron microscopy. Quantitative analysis showed that as early as 5 hours postlesion there was a dramatic increase in the density and morphological complexity of spines on the perikarya of the granule cells in rats that received seizure‐producing hilus lesions when compared to granule cells from control rats. Many of the somatic spines received asymmetric synapses. The increase in somatic spines was dependent on seizure activity and persisted for at least 1 month following a single recurrent seizure episode. CA1 pyramidal neurons, which exhibit changes in gene expression in response to hilus lesion‐induced seizures but do not normally possess somatic spines, did not exhibit an activity‐dependent elaboration of somatic spines. Thus, the seizure‐induced elaboration of somatic spines represents an amplification of an existing feature of the granule cells and not an effect occurring throughout hippocampus. These data provide evidence for very rapid and long‐lasting structural plasticity in response to brief episodes of seizure activity in the adult brain. © 1994 Wil

ISSN:1050-9631    

DOI:10.1002/hipo.450040510

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

年代:1994

数据来源: WILEY

摘要:

AbstractHilus lesion‐induced recurrent limbic seizures cause a dramatic increase in the numbers of somatic spines on dentate gyrus granule cells in the adult rat. Somatic spines are maximally increased 3 h after the initiation of seizures at which time many of these spines form synapses. The present quantitative electron microscopic study assessed the numbers and types of synapses present on the granule cell perikarya and somatic spines of control and experimental seizure rats with the goal of determining if newly elaborated somatic spines arise at the site of pre‐existing synapses or are associated with new innervation. Experimental rats were sacrificed 5 h after hilar lesion placement (or 3 h after seizure onset). In both control and hilus‐lesioned (HL) rats, 15–20% of the somatic spines could be seen to form synaptic contacts within a single plane of section; these synapses were almost exclusively of the asymmetric type. With the increased incidence of spines in experimental‐seizure rats, there was a 6.25‐fold greater number of spine synapses in HL versus control rats. There was, in addition, a 60% decrease in the number of asymmetric synapses occurring directly on the granule cell perikarya but no change in the total (spine plus somatic) number of asymmeteric synapses. Although few asymmetric synapses were associated with spines in control tissue, 60–70% of asymmetric synapses were associated with spines in experimental‐seizure tissue. In addition, in hilus lesion rats symmetric somatic synapses were increased by 20% on cells in deep stratum granulosum resulting in a dissolution of the superficial‐to‐deep innervation gradient present in the untreated rat. These findiings support the conclusion that spines induced by seizure activity form at the site of pre‐existing asymmetric synapses on the granule cells and demonstrate that brief seizure episodes can rapidly induce marked changes in innervation patterns in the adult brain.

ISSN:1050-9631    

DOI:10.1002/hipo.450040511

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

年代:1994

数据来源: WILEY