Dorsal Hippocampus (dorsal + hippocampus)

Distribution by Scientific Domains

Selected Abstracts

Effects of Potassium Concentration on Firing Patterns of Low-Calcium Epileptiform Activity in Anesthetized Rat Hippocampus: Inducing of Persistent Spike Activity

EPILEPSIA, Issue 4 2006
Zhouyan Feng
Summary:,Purpose: It has been shown that a low-calcium high-potassium solution can generate ictal-like epileptiform activity in vitro and in vivo. Moreover, during status epileptiform activity, the concentration of [K+]o increases, and the concentration of [Ca2+]o decreases in brain tissue. Therefore we tested the hypothesis that long-lasting persistent spike activity, similar to one of the patterns of status epilepticus, could be generated by a high-potassium, low-calcium solution in the hippocampus in vivo. Methods: Artificial cerebrospinal fluid was perfused over the surface of the exposed left dorsal hippocampus of anesthetized rats. A stimulating electrode and a recording probe were placed in the CA1 region. Results: By elevating K+ concentration from 6 to 12 mM in the perfusate solution, the typical firing pattern of low-calcium ictal bursts was transformed into persistent spike activity in the CA1 region with synaptic transmission being suppressed by calcium chelator EGTA. The activity was characterized by double spikes repeated at a frequency ,4 Hz that could last for >1 h. The analysis of multiple unit activity showed that both elevating [K+]o and lowering [Ca2+]o decreased the inhibition period after the response of paired-pulse stimulation, indicating a suppression of the after-hyperpolarization (AHP) activity. Conclusions: These results suggest that persistent status epilepticus,like spike activity can be induced by nonsynaptic mechanisms when synaptic transmission is blocked. The unique double-spike pattern of this activity is presumably caused by higher K+ concentration augmenting the frequency of typical low-calcium nonsynaptic burst activity. [source]

Effect of Dipotassium Clorazepate on Ainygdaloid-Kiiidling and Comparison Between Amygdaloid- and Hippocampal-Kindled Seizures in Rats

EPILEPSIA, Issue 2000
Kouichiro Amano
Purpose: We reportcd previously that dipotassium clorazcpate (potassium 7-chloro-2, 3-dihydro-2-oxo-S-phcnyI- l H- l, 4-bcnzodiazepinc-3-carboxylate potassium hydroxide: DC), an antianxiety drug, suppressed hippocampel kindled scizures in rats i n a dose-dependent manner (Amano et al. Psychiatry Clin Neuroscienccs 1998; 52: 459,462). Its effect on kindling, howcver, has not been evaluated. Moreover, differcnces in the anticonvulsive effccts of conventional anticonvulsants bctween amygdaloid-and hippocampal-kindlcd seizures have becn reportcd (Kamci et al. Arch. Int. Pharmacodyn I98 1; 249: 164,176). To clarify the anticonvulsive propcrties of DC, we examined its effects on amygdaloid kindling and compared it for 7 succcssive days against amygdaloid- and hippocampal-kindled seizures using thc rat kindling model of epilcpsy. Methods: Adult inale Wistar rata weighing 220,330 g werc used. Electrodes were implanted stereotaxically into thc left basoiatcfiil amygdala or the left dorsal hippocampus under pcntobarhital ancsthesia. Expcriment 1: Anticonvulsive effect on amygdaloid-kindled seizurcs. Rats having >5 consecutive stage-5 seimrcs were htimulated at the generalizcd seizure-triggering threshold (GST) intensity 30 minutes after i.p. administration or DC or saline. Experiment 2: Effect on amygdala kindling. In other groups of Tiits, the amygdala was stimulated once daily following 30 minutes i.p. administration or DC at 5 mg/kg or saline until the first stage-5 seizure was attained. Experimcnt 3: Comparison of anticonvulsive effect bctween amygdaloid- and hippocampal-kindled scizures. In other groups of rats having 5 consecutive stage-5 seizures, the GST was determined. Furthermorc, rats having >I0 stage-5 scizures induced at thc GST intensity were testcd once a day for 7 consecutive days. Thc stimulation was delivercd 30 minutes aftcr i.p. administration of DC or saline. Results: Expcriment I: DC suppresscd amygdaloid-kindled scizures in a dose-depcndent manner. Significant reduction of aftcr-discharge duration compared with the control group was observed at dosagcs of 2 mg/kg or more, hut complete suppression of after-discharges was observed in only I of 7 sessions at the highcst dose. Expcriment 2: Thc number of stimulations rcquired for the first stage-5 seiiurc in the 5 mg/kg dosage group was 14.1+1.4 stimulations, which was significantly greater than the 10.2+1.7 stimulations in the control group (P4.01). The contralateral cortical afterdischarge duration i n the DC treated group was signilicantly shortcr than thc afterdischarge duration in the amygdala at the first 7 stimulations, whereas it was significantly shorter only the first 3 stimulations i n the control group. Experiment 3: DC suppressed amygdaloid-kindled seizures at 2 and 5 mg/kg, whcreas I mg/kg or morc suppresscd hippocampal-kindlcd seizures. Conclusions: Thc result of the present study suggcst that thc principal anticonvulsive cffect of DC is likely to be relatcd mainly to attenuation of propagation of scizure activity rather than to an elevatcd seizure threshold, which may support our previously findings that increased stimulus intensity could not complctcly reverse thc anticonvulsive effects of DC. Thus, differences in effective dosages in both amygdaloid- and hippocampal-kindled seizures may suggcst a difference in the neuronal mechanisms that arc cvolved in this kindling. The present study dcmonstratcd that DC has a modest anticonvulsive effect without serious adverse effccts, which indicates thc clinical uscfulness of DC for treatment intractable epilepsy. [source]

Two-way active avoidance training-specific increases in phosphorylated cAMP response element-binding protein in the dorsal hippocampus, amygdala, and hypothalamus

Subhash Saha
Abstract Previous studies have demonstrated that the activation of pontine-wave (P-wave) generating cells in the brainstem during post-training rapid eye movement (REM) sleep is critical for the consolidation of memory for two-way active avoidance (TWAA) learning in the rat. Here, using immunocytochemistry, we investigated the spatio-temporal distribution of CREB phosphorylation within different parts of the dorsal hippocampus, amygdala, and hypothalamus following a session of TWAA training in the rat. We show that the TWAA training trials increased phosphorylation of CREB (p-CREB) in the dorsal hippocampus, amygdala, amygdalo-hippocampal junction (AHi), and hypothalamus. However, the time intervals leading to training-induced p-CREB activity were different for different regions of the brain. In the dorsal hippocampus, p-CREB activity was maximal at 90 min and this activity disappeared by 180 min. In the AHi, activity of the p-CREB peaked by 180 min and disappeared by 360 min. In the amygdala, the p-CREB activity peaked at 180 min and still remained higher than the control at the 360 min interval. In the hypothalamus, at 90 min p-CREB activity was present only in the ventromedial hypothalamus; however, by 180 min this p-CREB activity was also present in the dorsal hypothalamus, perifornical area, and lateral hypothalamus. By 360 min, p-CREB activity disappeared from the hypothalamus. This TWAA training trials-induced spatiotemporal characteristic of CREB phosphorylation, for the first time, suggests that REM sleep P-wave generator activation-dependent memory processing involves different parts of the dorsal hippocampus, amygdala, and hypothalamus. [source]

Dissociation of function between the dorsal and the ventral hippocampus in spatial learning abilities of the rat: a within-subject, within-task comparison of reference and working spatial memory

Helen H. J. Pothuizen
Abstract Lesions restricted to the dorsal, but not the ventral, hippocampus severely impair the formation of spatial memory. This dissociation was first demonstrated using the water maze task. The present study investigated whether the dorsal and the ventral hippocampus are involved differentially in spatial reference and spatial working memory using a four-baited/four-unbaited version of the eight-arm radial maze task. This test allows the concurrent evaluation of reference and working memory with respect to the same set of spatial cues, and thereby enables a within-subjects within-task comparison between the two forms of memory functions. Rats with N -methyl- d -aspartic acid-induced excitotoxic lesions of the dorsal hippocampus, ventral hippocampus or both were compared with sham and unoperated controls. We showed that dorsal lesions were as effective as complete lesions in severely disrupting both reference and working spatial memory, whereas rats with ventral lesions performed at a level comparable with controls. These results lend further support to the existence of a functional dissociation between the dorsal and the ventral hippocampus, with the former being preferentially involved in spatial learning. [source]

Rapid and long-term alterations of hippocampal GABAB receptors in a mouse model of temporal lobe epilepsy

Andrea Straessle
Abstract Alterations of ,-aminobutyric acid (GABA)B receptor expression have been reported in human temporal lobe epilepsy (TLE). Here, changes in regional and cellular expression of the GABAB receptor subunits R1 (GBR1) and R2 (GBR2) were investigated in a mouse model that replicates major functional and histopathological features of TLE. Adult mice received a single, unilateral injection of kainic acid (KA) into the dorsal hippocampus, and GABAB receptor immunoreactivity was analysed between 1 day and 3 months thereafter. In control mice, GBR1 and GBR2 were distributed uniformly across the dendritic layers of CA1,CA3 and dentate gyrus. In addition, some interneurons were labelled selectively for GBR1. At 1 day post-KA, staining for both GBR1 and GBR2 was profoundly reduced in CA1, CA3c and the hilus, and no interneurons were visible anymore. At later stages, the loss of GABAB receptors persisted in CA1 and CA3, whereas staining increased gradually in dentate gyrus granule cells, which become dispersed in this model. Most strikingly, a subpopulation of strongly labelled interneurons reappeared, mainly in the hilus and CA3 starting at 1 week post-KA. In double-staining experiments, these cells were selectively labelled for neuropeptide Y. The number of GBR1-positive interneurons also increased contralaterally in the hilus. The rapid KA-induced loss of GABAB receptors might contribute to epileptogenesis because of a reduction in both presynaptic control of transmitter release and postsynaptic inhibition. In turn, the long-term increase in GABAB receptors in granule cells and specific subtypes of interneurons may represent a compensatory response to recurrent seizures. [source]

Time-dependent enhancement of inhibitory avoidance retention and MAPK activation by post-training infusion of nerve growth factor into CA1 region of hippocampus of adult rats

Roger Walz
Abstract Several studies have demonstrated that chronic intracerebroventricular nerve growth factor (NGF) infusion has a beneficial effect on cognitive performance of lesioned as well as old and developing animals. Here we investigate: (i) the effect of post-training infusion of NGF into the CA1 region of hippocampus on inhibitory avoidance (IA) retention in rats; (ii) the extension of the effect, in time and space, of NGF infusion into CA1 on the activity of mitogen-activated protein kinase (MAPK, syn: ERK1/2, p42/p44 MAPK). NGF was bilaterally injected into the CA1 regions of the dorsal hippocampus (0.05, 0.5 or 5.0 ng diluted in 0.5 ,L of saline per side ) at 0, 120 or 360 min after IA training in rats. Retention testing was carried out 24 h after training. The injection of 5.0 and 0.5, but not 0.05, ng per side of NGF at 0 and 120 min after IA training enhanced IA retention. The highest dose used was ineffective when injected 360 min after training. The infusion of 0.5 ,L of NGF (5.0 ng) induced a significant enhancement of MAPK activity in hippocampal microslices; this enhancement was restricted to a volume with 0.8 mm radius at 30 min after injection. The MAPK activation was still seen 180 min after NGF infusion, although this value showed only a tendency. In conclusion, localized infusion of NGF into the CA1 region enhanced MAPK activity, restricted in time and space, and enhanced IA retention in a time- and dose-dependent manner. [source]

Mirtazapine enhances frontocortical dopaminergic and corticolimbic adrenergic, but not serotonergic, transmission by blockade of ,2 -adrenergic and serotonin2C receptors: a comparison with citalopram

M. J. Millan
Abstract Mirtazapine displayed marked affinity for cloned, human ,2A -adrenergic (AR) receptors at which it blocked noradrenaline (NA)-induced stimulation of guanosine-5,-O-(3-[35S]thio)-triphosphate ([35S]-GTP,S) binding. Similarly, mirtazapine showed high affinity for cloned, human serotonin (5-HT)2C receptors at which it abolished 5-HT-induced phosphoinositide generation. Alpha2 -AR antagonist properties were revealed in vivo by blockade of UK-14,304-induced antinociception, while antagonist actions at 5-HT2C receptors were demonstrated by blockade of Ro 60 0175-induced penile erections and discriminative stimulus properties. Mirtazapine showed negligible affinity for 5-HT reuptake sites, in contrast to the selective 5-HT reuptake inhibitor, citalopram. In freely moving rats, in the dorsal hippocampus, frontal cortex (FCX), nucleus accumbens and striatum, citalopram increased dialysate levels of 5-HT, but not dopamine (DA) and NA. On the contrary, mirtazapine markedly elevated dialysate levels of NA and, in FCX, DA, whereas 5-HT was not affected. Citalopram inhibited the firing rate of serotonergic neurons in dorsal raphe nucleus, but not of dopaminergic neurons in the ventral tegmental area, nor adrenergic neurons in the locus coeruleus. Mirtazapine, in contrast, enhanced the firing rate of dopaminergic and adrenergic, but not serotonergic, neurons. Following 2 weeks administration, the facilitatory influence of mirtazapine upon dialysate levels of DA and NA versus 5-HT in FCX was maintained, and the influence of citalopram upon FCX levels of 5-HT versus DA and NA was also unchanged. Moreover, citalopram still inhibited, and mirtazapine still failed to influence, dorsal raphe serotonergic neurons. In conclusion, in contrast to citalopram, mirtazapine reinforces frontocortical dopaminergic and corticolimbic adrenergic, but not serotonergic, transmission. These actions reflect antagonist properties at ,2A -AR and 5-HT2C receptors. [source]

Memory retrieval after contextual fear conditioning induces c-Fos and JunB expression in CA1 hippocampus

T. Strekalova
Using specific polyclonal antisera against c-Fos, JunB, c-Jun and JunD, we tried to identify the candidate transcription factors of the immediate early gene family which may contribute to the molecular processes during contextual memory reconsolidation. For that purpose we analyzed the expression of these proteins in the hippocampus after contextual memory retrieval in a mouse model of fear conditioning. A single exposure to a foot shock of 0.8 mA was sufficient to induce robust contextual fear conditioning in C57Bl/6N mice. In these mice context dependent memory retrieval evoked a marked induction of c-Fos and JunB, but not of c-Jun and JunD, in pyramidal CA1 neurons of the dorsal hippocampus. In contrast, mice exposed and re-exposed only to the context, without foot shock, did not show behavioral signs of contextual fear conditioning and exhibited significantly less expression of c-Fos and JunB in CA1 neurons. Mice which received a foot shock but were not re-exposed to the context revealed no immediate early gene induction. These results demonstrate that contextual memory retrieval is associated with de novo synthesis of specific members of the Fos/Jun transcription factor family. Therefore we suggest that these genes may contribute to plasticity and reconsolidation accompanying the retrieval process. The specific activation of CA1 neurons during the retrieval of contextual fear associations supports the postulated concept of a mnemonic role of this hippocampal subsector during the retrieval of contextual informations. [source]

PKM, maintains 1-day- and 6-day-old long-term object location but not object identity memory in dorsal hippocampus

HIPPOCAMPUS, Issue 6 2010
Oliver Hardt
Abstract Continuous activity of the atypical protein kinase C isoform M zeta (PKM,) is necessary for maintaining long-term memory acquired in aversively or appetitively motivated associative learning tasks, such as active avoidance, aversive taste conditioning, auditory and contextual fear conditioning, radial arm maze, and watermaze. Whether unreinforced, nonassociative memory will also require PKM, for long-term maintenance is not known. Using recognition memory for object location and object identity, we found that inactivating PKM, in dorsal hippocampus abolishes 1-day and 6-day-old long-term recognition memory for object location, while recognition memory for object identity was not affected by this treatment. Memory for object location persisted for no more than 35 days after training. These results suggest that the dorsal hippocampus mediates long-term memory for where, but not what things have been encountered, and that PKM, maintains this type of spatial knowledge as long as the memory exists. © 2009 Wiley-Liss, Inc. [source]

Effects of pre or posttraining dorsal hippocampus D-AP5 injection on fear conditioning to tone, background, and foreground context

HIPPOCAMPUS, Issue 11 2008
Eduardo Ekman Schenberg
Abstract NMDA receptor antagonist D-AP5 was injected into the dorsal hippocampus of Wistar rats before or immediately after the training session in fear conditioning. Training was conducted both with signaled (background context) or unsignaled (foreground context) footshocks. Contextual fear conditioning was assessed 24 h later and tone fear conditioning 48 h after training (only in the signaled footshock condition). Pretraining injections impaired conditioned fear to contextual features, both in background and foreground configurations, whereas tone fear conditioning was left intact. Posttraining injections were ineffective in all cases. We conclude that dorsal hippocampal NMDA receptors are required for contextual fear acquisition independently of context saliency and that they are not required to early consolidation processes. © 2008 Wiley-Liss, Inc. [source]

Nicotinic acetylcholine receptor expression in the hippocampus of 27 mouse strains reveals novel inhibitory circuitry

HIPPOCAMPUS, Issue 8 2008
Lorise C. Gahring
Abstract Mouse strains are well-characterized to exhibit differences in their physiological and behavioral responses to nicotine. This report examines the expression of the high-affinity nicotine binding receptor subunit, neuronal nicotinic receptor subunit alpha4 (nAChR,4), in the dorsal hippocampus of 27 inbred mouse strains. Multiple differences among mouse strains in the cellular expression of nAChR,4 between subregions of the hippocampal field are evident. Differences that we describe in the expression of nAChR,4 suggest mouse strains of diverse genetic origin could exhibit significant variation in how this receptor contributes to modulating intrahippocampal circuitry. These findings define a genetic frame-work in which the strain-specific responses to nicotine include underlying contributions by the varied anatomical context in which nAChRs are expressed. © 2008 Wiley-Liss, Inc. [source]

Mouse chromosome 11 harbors genetic determinants of hippocampal strain-specific nicotinic receptor expression

HIPPOCAMPUS, Issue 8 2008
Scott W. Rogers
Abstract Differences between isogenic mouse strains in cellular expression of the neuronal nicotinic acetylcholine (ACh) receptor subunit alpha4 (nAChR,4) by the dorsal hippocampus are well known. To investigate further the genetic basis of these variations, expression of the nAChR,4 subunit was measured in congenic mouse lines derived from two strains exhibiting notable divergence in the expression of this subunit: C3H and C57BL/6. Congenic lines carrying reciprocally introgressed regions (quantitative trait loci; QTL) from chromosomes 4, 5, and 12 each retained the phenotype most closely associated with the parental strain. However, in congenic lines harboring the reciprocal transfer of a chromosome 11 QTL, a characteristic difference in the ratio of interneurons versus astrocytes expressing nAChR,4 in the CA1 region is reversed relative to the parental strain. These finding suggest that this chromosomal segment harbors genes that regulate strain distinct hippocampal morphology that is revealed by nAChR,4 expression. © 2008 Wiley-Liss, Inc. [source]

Dorsal hippocampus involvement in delay fear conditioning depends upon the strength of the tone-footshock association

HIPPOCAMPUS, Issue 7 2008
Jennifer J. Quinn
Abstract The hippocampus is important for the formation of spatial, contextual, and episodic memories. For instance, lesions of the dorsal hippocampus (DH) produce demonstrable deficits in contextual fear conditioning. By contrast, it is generally agreed that the DH is not important for conditioning to a discrete cue (such as a tone or light) that is paired with footshock in a temporally contiguous fashion (delay conditioning). There are, however, some reports of hippocampus involvement in delay conditioning. The present series of experiments was designed to assess the conditions under which the hippocampus-dependent component of delay fear conditioning performance may be revealed. Here, we manipulated the number of conditioning trials and the intensity of the footshock in order to vary the strength of conditioning. The results indicate that the DH contributes to freezing performance to a delay conditioned tone when the conditioning parameters are relatively weak (few trials or low footshock intensity), but not when strong parameters are used. The results are discussed in terms of two parallel memory systems: a direct tone-footshock association that is independent of the hippocampus and a hippocampus-dependent memory for the conditioning session. © 2008 Wiley-Liss, Inc. [source]

Different behavioral effects of neurotoxic dorsal hippocampal lesions placed under either isoflurane or propofol anesthesia

HIPPOCAMPUS, Issue 3 2008
Mark G. Baxter
Abstract Anesthetic protocols for behavioral neuroscience experiments are evolving as new anesthetics are developed and surgical procedures are refined to improve animal welfare. We tested whether neurotoxic dorsal hippocampal lesions produced under two different anesthetic protocols would have different behavioral and/or histo-pathological effects. Rats were anesthetized with either propofol, an intravenous anesthetic, or isoflurane, a gaseous anesthetic, and multiple injections of an excitotoxin (N -methyl- D -aspartate) were stereotaxically placed in the dorsal hippocampus bilaterally. Intraoperative physiological parameters were similar in the two surgical groups, as were the volumes of the lesions, although the profile of postoperative impairment in a spatial learning task differed between the lesion groups depending on the anesthetic regimen used. These results show that the choice of anesthetic protocol is a critical variable in designing behavioral neuroscience experiments using neurosurgical procedures. This factor should be considered carefully in experimental design and in cross-study comparisons of lesion effects on behavior. © 2007 Wiley-Liss, Inc. [source]

Differential involvement of the dorsal hippocampus in passive avoidance in C57bl/6J and DBA/2J mice

HIPPOCAMPUS, Issue 1 2008
Petra J.J. Baarendse
Abstract The inferior performance of DBA/2 mice when compared to C57BL/6 mice in hippocampus-dependent behavioral tasks including contextual fear conditioning has been attributed to impaired hippocampal function. However, DBA/2J mice have been reported to perform similarly or even better than C57BL/6J mice in the passive avoidance (PA) task that most likely also depends on hippocampal function. The apparent discrepancy in PA versus fear conditioning performance in these two strains of mice was investigated using an automated PA system. The aim was to determine whether these two mouse strains utilize different strategies involving a different contribution of hippocampal mechanisms to encode PA. C57BL/6J mice exhibited significantly longer retention latencies than DBA/2J mice when tested 24 h after training irrespective of the circadian cycle. Dorsohippocampal NMDA receptor inhibition by local injection of the selective antagonist DL -2-amino-5-phosphonovaleric acid (AP5, 3.2 ,g/mouse) before training resulted in impaired PA retention in C57BL/6J but not in DBA/2J mice. Furthermore, nonreinforced pre-exposure to the PA system before training caused a latent inhibition-like reduction of retention latencies in C57BL/6J, whereas it improved PA retention in DBA/2J mice. These pre-exposure experiments facilitated the discrimination of hippocampal involvement without local pharmacological intervention. The results indicate differences in PA learning between these two strains based on a different NMDA receptor involvement in the dorsal hippocampus in this emotional learning task. We hypothesize that mouse strains can differ in their PA learning performance based on their relative ability to form associations on the basis of unisensory versus multisensory contextual/spatial cues that involve hippocampal processing. © 2007 Wiley-Liss, Inc. [source]

Cooperation and competition between the dorsal hippocampus and lateral amygdala in spatial discrimination learning

HIPPOCAMPUS, Issue 7 2006
Stephane Gaskin
Abstract The conditioned cue preference (CCP) was used to study how rats discriminate between adjacent arms on a radial maze. Chai and White (Behav Neurosci 2004, 118:770,784) showed that an intact dorsal hippocampus is required to learn this discrimination and that an amygdala-based conditioned approach response that produces an equal tendency to enter both arms is simultaneously acquired. In the present experiments, rats were preexposed to the maze with no food and trained by alternately confining them at the ends of two adjacent arms, one that contained food and one that did not. When given a choice between these arms with no food present, the rats spent more time on their food-paired arms, suggesting they had learned to discriminate their locations. Temporary inactivation of the dorsal hippocampus with muscimol during confinement on the food-paired arm had no effect on the discrimination, but inactivation while on the no-food arm impaired it. This pattern of effects was reversed in rats with amygdala lesions (inactivation on the food-paired arm impaired, but inactivation on the no-food arm had no effect on the discrimination), showing that hippocampus-based and amygdala-based learning interact to influence the behavior of normal rats in this situation. The dorsal hippocampus learns about locations that contain food and about locations that do not contain food. The amygdala-based tendency to enter the food-paired arm cooperates with hippocampus-based foraging for food on the food-paired, but the amygdala-based tendency to enter the no-food arm competes with hippocampus-based learning about the absence of food on that arm. © 2006 Wiley-Liss, Inc. [source]

Self-motion and the origin of differential spatial scaling along the septo-temporal axis of the hippocampus

HIPPOCAMPUS, Issue 7 2005
Andrew P. Maurer
Abstract Spatial scaling of place specific activity in the hippocampus varies systematically from the septal pole (high resolution) to the temporal pole (low resolution). Place fields get progressively larger, and the probability of observing a field in a given environment gets progressively smaller. It was previously found that decoupling movement in space from ambulation, by having the animal actively ride on a mobile platform, results in marked enlargement of the spatial scale factor in the dorsal hippocampus and a reduction in the increase in theta rhythm power with running speed, suggesting that a self-motion signal determines the spatial scale at which the hippocampal population vector updates. These results led to the hypothesis that the gain of the self-motion signal may vary systematically along the septo-temporal axis of the hippocampus. To test this hypothesis, EEG theta rhythm and ensembles of CA1 pyramidal cells and interneurons were recorded from the extreme dorsal and middle portions of the hippocampus. Pyramidal cell population vectors representing successive locations became decorrelated over substantially shorter distances in the dorsal than in the middle hippocampus. Dorsal pyramidal cells had smaller place fields, higher mean and peak firing rates, and higher intrinsic oscillation frequencies during track running than that of middle pyramidal cells. Both dorsal pyramidal cells and interneurons had more elevated mean rates during running, compared with rest, than that of the corresponding cell classes in the middle hippocampus, and both cell classes increased their rates more as a function of speed in the dorsal hippocampus. The amplitude, but not the frequency of fissure recorded theta rhythm, increased more as a function of running speed in the dorsal than in the middle hippocampus. We conclude that variation in the neuronal response to movement speed is the likely basis for the systematic variation in spatial scaling along the septo-temporal axis of the hippocampus. © 2005 Wiley-Liss, Inc. [source]

Time-dependent involvement of the dorsal hippocampus in trace fear conditioning in mice

HIPPOCAMPUS, Issue 4 2005
Ilga Misane
Abstract Hippocampal and amygdaloid neuroplasticity are important substrates for Pavlovian fear conditioning. The hippocampus has been implicated in trace fear conditioning. However, a systematic investigation of the significance of the trace interval has not yet been performed. Therefore, this study analyzed the time-dependent involvement of N-methyl- D -aspartate (NMDA) receptors in the dorsal hippocampus in one-trial auditory trace fear conditioning in C57BL/6J mice. The NMDA receptor antagonist APV was injected bilaterally into the dorsal hippocampus 15 min before training. Mice were exposed to tone (conditioned stimulus [CS]) and footshock (unconditioned stimulus [US]) in the conditioning context without delay (0 s) or with CS-US (trace) intervals of 1,45 s. Conditioned auditory fear was determined 24 h after training by the assessment of freezing and computerized evaluation of inactivity in a new context; 2 h later, context-dependent memory was tested in the conditioning context. NMDA receptor blockade by APV markedly impaired conditioned auditory fear at trace intervals of 15 s and 30 s, but not at shorter trace intervals. A 45-s trace interval prevented the formation of conditioned tone-dependent fear. Context-dependent memory was always impaired by APV treatment independent of the trace interval. The results indicate that the dorsal hippocampus and its NMDA receptors play an important role in auditory trace fear conditioning at trace intervals of 15,30-s length. In contrast, NMDA receptors in the dorsal hippocampus are unequivocally involved in contextual fear conditioning independent of the trace interval. The results point at a time-dependent role of the dorsal hippocampus in encoding of noncontingent explicit stimuli. Preprocessing of long CS-US contingencies in the hippocampus appears to be important for the final information processing and execution of fear memories through amygdala circuits. © 2005 Wiley-Liss, Inc. [source]

Excitotoxic lesions of the pre- and parasubiculum disrupt the place fields of hippocampal pyramidal cells

HIPPOCAMPUS, Issue 1 2004
Ping Liu
Abstract To determine what influence the pre- and parasubiculum regions of the hippocampal formation have on neural representations within the dorsal hippocampus, single-unit recordings were made as rats with bilateral ibotenic acid lesions centered on the former regions (n = 4) or control surgeries (n = 3) foraged freely. Spatial firing specificity was measured using an information content procedure. Cells from lesioned animals (n = 57) provided significantly less spatial information than cells from control animals (n = 44). Whereas some degree of location-related activity (place fields) was observed in 98% of neurons recorded from control animals, it was observed in only 65% of the neurons from lesioned animals. The spatial resolution of the intact place fields appeared to be compromised in lesioned animals as a result of their having a higher firing rate outside the place field. These findings indicate that the pre- and parasubiculum regions have a major role in maintaining the specificity of the place field firing of hippocampal pyramidal cells. Since previous data indicate that these lesioned animals displayed delay-dependent deficits in spatial tasks, these findings also suggest that a disruption in place field activity may be a causal factor in this spatial memory deficit. © 2003 Wiley-Liss, Inc. [source]

Involuntary, unreinforced (pure) spatial learning is impaired by fimbria-fornix but not by dorsal hippocampus lesions

HIPPOCAMPUS, Issue 3 2003
Norman M. White
Abstract Pure spatial learning occurs when rats acquire information about an environment while exploring it in the absence of reinforcers. We previously reported that voluntary, unreinforced exploration of a radial maze retards subsequent reinforced conditioned cue preference (CCP) learning in the same maze. In the present experiment, we examined the effects of involuntary, unreinforced pre-exposure to a radial maze. During pre-exposure, rats were moved by an experimenter between the ends of two arms of a radial maze five times in 30 min. This form of pre-exposure retarded CCP learning, whereas rats that were not pre-exposed and rats that were pre-exposed to a maze in a different room displayed normal CCP learning. These findings suggest that some information specific to the maze environment was acquired during involuntary unreinforced pre-exposure to it. In experiment 2, the retardation of reinforced CCP learning by involuntary unreinforced pre-exposure was eliminated by fimbria-fornix lesions made before pre-exposure but was unaffected by fimbria-fornix lesions made after pre-exposure but before training. Large neurotoxic lesions of the dorsal hippocampus made before pre-exposure had no effect on the retardation of CCP learning, but the rats with these lesions were impaired on a standard test of reinforced spatial learning in a water maze. The lesion effects in experiment 2 are similar to those previously reported for voluntary exploration and suggest that pure spatial learning may occur during both voluntary exploration of and involuntary exposure to an environment in the absence of reinforcers. Pure spatial learning can apparently occur with exposure to two different locations within an environment, but the rats do not have to move between the locations voluntarily. An intact fimbria-fornix is required for acquisition but not expression of this form of learning. The hippocampus is not involved in this form of learning. Hippocampus 2003;13:324,333. © 2003 Wiley-Liss, Inc. [source]

Post-training reversible inactivation of hippocampus reveals interference between memory systems

HIPPOCAMPUS, Issue 2 2002
Jason P. Schroeder
Abstract A post-training reversible lesion technique was used to examine the effects of neural inactivation of the dorsal hippocampus on place and response learning. Male Long-Evans rats trained in one of two versions of a water plus-maze task received post-training intra-hippocampal infusions of the local anesthetic drug bupivacaine (0.75% solution, 0.5 ,l), or saline. Post-training intra-hippocampal infusions of bupivacaine attenuated acquisition of the place task and enhanced acquisition of the response task. Delayed (2-h) post-training infusions of bupivacaine did not affect retention in either task. The findings demonstrate (1) enhanced learning after reversible hippocampal lesions that is independent of treatment influences on non-mnemonic factors, and (2) inactivation of the dorsal hippocampus during the post-training memory consolidation period is sufficient to enhance response learning. Hippocampus 2002;12:280,284. © 2002 Wiley-Liss, Inc. [source]

NAAG peptidase inhibitor increases dialysate NAAG and reduces glutamate, aspartate and GABA levels in the dorsal hippocampus following fluid percussion injury in the rat

Chunlong Zhong
Abstract Traumatic brain injury (TBI) produces a rapid and excessive elevation in extracellular glutamate that induces excitotoxic brain cell death. The peptide neurotransmitter N -acetylaspartylglutamate (NAAG) is reported to suppress neurotransmitter release through selective activation of presynaptic group II metabotropic glutamate receptors. Therefore, strategies to elevate levels of NAAG following brain injury could reduce excessive glutamate release associated with TBI. We hypothesized that the NAAG peptidase inhibitor, ZJ-43 would elevate extracellular NAAG levels and reduce extracellular levels of amino acid neurotransmitters following TBI by a group II metabotropic glutamate receptor (mGluR)-mediated mechanism. Dialysate levels of NAAG, glutamate, aspartate and GABA from the dorsal hippocampus were elevated after TBI as measured by in vivo microdialysis. Dialysate levels of NAAG were higher and remained elevated in the ZJ-43 treated group (50 mg/kg, i.p.) compared with control. ZJ-43 treatment also reduced the rise of dialysate glutamate, aspartate, and GABA levels. Co-administration of the group II mGluR antagonist, LY341495 (1 mg/kg, i.p.) partially blocked the effects of ZJ-43 on dialysate glutamate and GABA, suggesting that NAAG effects are mediated through mGluR activation. The results are consistent with the hypothesis that inhibition of NAAG peptidase may reduce excitotoxic events associated with TBI. [source]

Viral vectors carrying NR1 sequences injected into rat hippocampus interfered with learning and memory

V. Cheli
NMDA receptors are relevant to learning and memory as has been shown both by pharmacological and genetic manipulations. Gene knockouts are useful for investigating in vivo functions, but genetic deletions unrestricted in time or region, may lead to developmental defects or death. The challenge is to control expression with temporal and spatial restrictions in the brain. Viral vectors derived from herpes type-1 neurotropic virus are interesting candidates for it. To regulate gene expression of the NMDA receptor NR1 subunit, vectors carrying either sense NR1(+) or antisense NR1(,) sequences and that of the green fluorescent protein (GFP), were constructed. The protein or RNA expression were corroborated in cell culture by GFP autofluorescence, Western blots, immunofluorescence and RT-PCR, and in rat brain, by Western blots and GFP autofluorescence. The vectors were injected into the dorsal hippocampus of adult male Wistar rats. After 6 days each rat was trained and evaluated for both habituation to an open field and inhibitory avoidance to a foot-shock. The rats injected with GFP-NR1(+) vectors showed habituation and learned the inhibitory avoidance, like sham operated rats; while animals injected with GFP-NR1(,) vectors did not. The vectors were useful to modify endogenous gene expression at a defined period, in restricted regions, leading to investigate in vivo functions. NR1 subunit in the hippocampus is involved in mechanisms leading to habituation and to avoidance behaviour, since even a slight change in the availability of NR1 interfered with them. [source]

Exacerbated loss of cell survival, neuropeptide Y-immunoreactive (IR) cells, and serotonin-IR fiber lengths in the dorsal hippocampus of the aged flinders sensitive line "depressed" rat: Implications for the pathophysiology of depression?

H. Husum
Abstract Impairment of hippocampal neurogenesis has been proposed to provide a cellular basis for the development of major depression. Studies have shown that serotonin (5-HT) and neuropeptide Y (NPY) may be involved in stimulating cell proliferation in the dentate gyrus. The Flinders-sensitive line (FSL) rat represents a genetic model of depression with characterized 5-HT and NPY abnormalities in the hippocampus. Consequently, it could be hypothesized that hippocampal neurogenesis in the FSL rat would be impaired. The present study examined the relationship among 1) number of BrdU-immunoreactive (IR) cells, 2) NPY-IR cells in the dentate gyrus, and 3) length of 5-HT-IR fibers in the dorsal hippocampus, as well as volume and number of 5-HT-IR cells in the dorsal raphé nucleus, in adult and aged FSL rats and control Flinders-resistant line (FRL) rats. Surprisingly, adult FSL rats had significantly more BrdU-IR and NPY-IR cells compared with adult FRL rats. However, aging caused an exacerbated loss of these cell types in the FSL strain compared with FRL. The aged FSL rats also had shortened 5-HT-IR fibers in the dorsal hippocampus, indicative of an impaired 5-HT innervation of this area, compared with FRL. These results suggest that, for "depressed" FSL rats, compared with FRL rats, aging is associated with an excacerbated loss of newly formed cells in addition to NPY-IR cells and 5-HT-IR dendrites in the hippocampus. These observations may be of relevance to the depression-like behavior of the FSL rat and, by inference, to the pathophysiology of depression. © 2006 Wiley-Liss, Inc. [source]