Spatial learning in the holeboard impairs an early phase of long-term potentiation in the rat hippocampal CA1-region

Long-term potentiation (LTP) and depression (LTD) are considered as cellular models for learning and memory. We studied the impact of holeboard training on LTP in the rat CA1 hippocampal region. In 7-week-old Wistar rats a recording electrode was chronically implanted into the hippocampal pyramidal cell layer of the CA1 of the right hemisphere and a stimulation electrode into the contralateral CA3 region.Two groups of animals received a spatial holeboard training of 10 or 15 trials over 2 days on a fixed pattern of baited holes. The last trial was performed 15 min after a primed burst stimulation of the contralateral CA3, which resulted in LTP in the ipsilateral CA1. A pseudo-trained group that received a 10 trial training with changing patterns of baited holes after each trial and a group that remained in the recording chambers during the experiments served as controls. Experimental rats significantly improved their spatial performance with increasing numbers of trials, indicated by decreasing times to pick up all food pellets and by decreasing numbers of reference memory errors. A learning-related impairment of CA1-LTP measured in both the population-spike amplitude as well as the fEPSP could be noted. These results show that specific (pattern-training), but not unspecific (pseudo-training) spatial information processing prior to electrical stimulation can severely affect LTP in hippocampal area CA1.     

Impairment of spatial learning and hippocampal synaptic potentiation in c-kit mutant rats

The c-kit receptor tyrosine kinase encoded by the white-spotting (W) gene is highly expressed in rat hippocampal CA1–CA4 regions. We found an impaired spatial learning and memory in homozygous c-kit (Ws/Ws) mutant rats that have a 12-base deletion in the tyrosine kinase domain of the c-kit gene and a very low kinase activity. Electrophysiological studies in hippocampal slices revealed that the long-term potentiation (LTP) induced by the tetanic stimulation (100 Hz, 1 sec) in the mossy fiber (MF)–CA3 pathway, but not in the Schaffer collaterals/commissural–CA1 pathway, was significantly reduced in c-kit mutants compared with wild-type (+/+) rats. The paired-pulse facilitation (PPF) was measured before the tetanus and after the establishment of the LTP in each slice. The initial PPF in the MF–CA3 pathway positively correlated with the amplitude of the LTP in the wild-type rats but not in the c-kit mutant rats. Furthermore, they failed to show the normal characteristics observed in the MF–CA3 pathway of +/+ rats; that is, the negative correlation between the initial PPF and the changes in PPF measured after the LTP. These findings suggest an involvement of SCF/c-kit signaling in hippocampal synaptic potentiation and spatial learning and memory.     

Differential Effects of Global Ischemia on Delayed Matching- and Non-Matching-to-Position Tasks in the Water Maze and Skinner Box

In order to assess effects of global ischemia in tasks of spatial learning and working memory, male Wistar rats were subjected to four vessel occlusion (4 VO) for periods of 5, 10, and 20 min and compared with sham-operated controls over four test phases, from 6 to 54 weeks after surgery. Rats were assessed on acquisition in the water maze, a task that is sensitive to ischemic impairments, before testing in Skinner box and water maze working memory tasks, which both require the short-term storage of information, but make different demands on spatial information processing. Phases 1 and 3 assessed spatial learning in a standard water maze procedure (12 and 10 training days, 2 trials/day with a 10-min intertrial interval: ITI). Phase 2 involved training and testing in delayed non-matching-to-position task in the Skinner box, with delays of 2–10 s between the information and choice stages. Phase 4 examined working memory in a water maze delayed matching-to-position task with 4 trials/day, an ITI of 30 s, and a novel platform position on each day. Ischemic rats showed duration-related impairments in water maze acquisition and working memory, but not in the less spatially demanding Skinner box task. Since water maze acquisition deficits were seen both before and after testing in the Skinner box the lack of effect cannot be attributed to time or to prior training. Ischemic deficits were more marked in Phase 3 than in Phase 1 of acquisition, suggesting that impairment may be progressive. Histological assessment showed that cell loss was largely confined to the hippocampal CA1 field and was linearly related to duration of occlusion. At the maximal level of loss (5.7 mm before the interaural line) the 20-min group showed 90% loss, the 10-min group 60% loss, and the 5-min group, which did not differ from controls, less than 10% loss. Only the 20-min group showed significant damage beyond the CA1 field, ranging from 30–40% loss in the CA3 field to 5% loss in one striatal area. No cortical damage was seen. The extent of CA1 cell loss correlated modestly with water maze acquisition (Phase 3) and working memory scores, but not with trials to criterion in the Skinner box task. There were significant correlations between different measures both within and between water maze tasks, but not Skinner box tasks, suggesting that the two types of procedure engaged different cognitive processes. The results indicate that the intrahippocampal damage induced by 4 VO impaired tasks which required processing of allocentric spatial information, but did not impair the storage of limited spatial information in working memory.     

Activation and survival of immature neurons in the dentate gyrus with spatial memory is dependent on time of exposure to spatial learning and age of cells at examination

Neurogenesis continues to occur throughout life in the dentate gyrus of the hippocampus and may be related to hippocampus-dependent learning. We have recently reported that there is an enhancement of neurogenesis in the hippocampus only when BrdU is administered 6 days prior to starting spatial training but not when training started either 1 day or 11 days following BrdU administration. In that study, all rats were perfused on day 16 after BrdU injection in order to compare cells of the same age (i.e. 16 day old cells) and thus the survival time after learning was different between groups. This study was designed to address whether the amount of time that passed following training could also contribute to the effects of spatial learning on hippocampal neurogenesis and whether there was differential new neuron activation in response to spatial learning that depended on the age of new cells at the time of spatial learning. Here we tested whether a survival period of 5 days following spatial learning at either 1-5, 6-10 or 11-15 days following BrdU administration would alter cell survival and/or activation of new neurons. Our results indicate that 5 days after training in the Morris water task cell survival is unaltered by training on days 1-5, increased by training at days 6-10 and decreased when training occurs on days 11-15. Furthermore spatial learners trained on days 6-10 or 11-15 show greater activation of new neurons compared to cue-trained rats during a probe trial 5 days after training. In addition, rats trained on the spatial task on days 11-15 had a greater number of activated new neurons compared to rats trained on the spatial task on days 6-10. These results suggest there is a gradual removal of older BrdU-labeled new neurons following spatial learning perhaps due to a competitive interaction with a population of younger BrdU-labeled new neurons.     

Hippocampal expression of the orphan nuclear receptor gene hzf-3/nurr1 during spatial discrimination learning

The immediate-early gene hzf-3, also known as nurr1, is a member of the inducible orphan nuclear receptor family and is one candidate in the search for genes associated with learning and memory processes. Here we report that acquisition of a spatial food search task is accompanied by elevated levels of hzf-3 mRNA in the hippocampus. Adult male Long-Evans rats were handled, food-restricted, and allowed to habituate to the maze prior to training. During acquisition, rats were given one training session per day for 5 days. Each training session consisted of five trials in which animals searched the maze for food located in 4 of 16 holes in the floor of the maze. Training resulted in spatial acquisition of the task. Northern blot analysis showed significant increases in hippocampal hzf-3 mRNA 3 h after training in the maze. Next, brains were obtained from Naive, Habituated, Day 1, Day 3, and Day 5 animals and processed for in situ hybridization. The results showed significant increases of hzf-3 mRNA in CA1 and CA3 subregions of the dorsal hippocampus during acquisition of the task. We conclude that expression of the hzf-3 gene in the brain is associated with long-term spatial memory processes. The present results are the first to implicate an orphan nuclear receptor in long-term information storage in the hippocampus.     

Involvement of hippocampal nitric oxide in spatial learning in the rat

Nitric oxide (NO) is thought to be involved in synaptic plasticity contributing to learning and memory in several brain areas including the hippocampus. The hippocampus is believed to have a critical role in the processing of spatial information. But, data on the role of hippocampal NO in spatial learning are not consistent. So the effect of NO synthase (NOS) inhibition in the CA1 region of rat hippocampus on spatial localization was investigated in the Morris water maze (MWM). Male albino Wistar rats cannulated in their CA1 region received bilateral injections of vehicle (saline) or N(omega)-nitro-L-arginine methyl ester (L-NAME), a NOS inhibitor (50, 100 and 200 microg/0.5 microl) through the cannulae 30 min before training each day. Animals were subjected to 5 days of training in the MWM; 4 days with the invisible platform to test spatial learning and the 5th day with the visible platform to test motivation and sensorimotor coordination. The results showed dose-dependent increases (p<0.001) in escape latency, traveled distance, heading angle, and dose-dependent decreases (p<0.01) in target quadrant entries in L-NAME-received groups as compared to the control group. This impairment was reversed by co-administration of mole-equivalent doses of L-arginine (L-Arg), the NO precursor. L-Arg alone at the dose of 129.2 microg, increased heading angle (p<0.01) with no effect on other parameters. On the basis of the present data, it is concluded that processes mediated by NO synthesis in the hippocampus are essentially involved in spatial learning.     

Enhanced Hippocampal CA1 LTP but Normal Spatial Learning in Inositol 1,4,5-trisphosphate 3-kinase(A)-Deficient Mice

To define the physiological role of IP₃3-kinase(A) in vivo, we have generated a mouse strain with a null mutation of the IP₃3-kinase(A) locus by gene targeting. Homozygous mutant mice were fully viable, fertile, apparently normal, and did not show any morphological anomaly in brain sections. In the mutant brain, the IP₄ level was significantly decreased whereas the IP₃ level did not change, demonstrating a major role of IP₃3-kinase(A) in the generation of IP₄. Nevertheless, no significant difference was detected in the hippocampal neuronal cells of the wild-type and the mutant mice in the kinetics of Ca²⁺ regulation after glutamate stimulation. Electrophysiological analyses carried out in hippocampal slices showed that the mutation significantly enhanced the LTP in the hippocampal CA1 region, but had no effect on the LTP in dentate gyrus (DG). No difference was noted, however, between the mutant and the wild-type mice in the Morris water maze task. Our results indicate that IP₃3-kinase(A) may play an important role in the regulation of LTP in hippocampal CA1 region through the generation of IP₄, but the enhanced LTP in the hippocampal CA1 does not affect spatial learning and memory.     

Differential involvement of hippocampal calcineurin during learning and reversal learning in a Y-maze task

The regulation and function of the calcium-dependent phosphatase calcineurin (CaN, protein phosphatase 2B) in learning and memory remain unclear, although recent work indicates that CaN may play a differential role in training and reversal training. To gain more insight into the involvement of CaN in these two types of learning, hippocampal CaN activity, protein levels, and expression patterns were studied in mice subjected to a reference memory version of the Y-maze task. We show that (1) training but not habituation induces a decrease in cytosolic CaN activity, (2) the recovery of cytosolic CaN activity is reversal training specific and does not reflect normal restoration of basal levels unrelated to subsequent learning, (3) cytosolic protein levels for the catalytic subunit of CaN (CaNA) are decreased at the early phase of training, but not at the early phase of reversal training, (4) CaNA immunoreactivity in the dorsal hippocampus is enhanced in the CA1 and CA3 area (but not in the dentate gyrus [DG] or subiculum [SUB]) only during reversal training. These findings indicate that memory formation is accompanied by reduced CaN activity, whereas adapting to changes in a familiar environment is accompanied by restored CaN activity. Moreover, reversal training selectively affects hippocampal CA3 and CA1 regions, suggesting a specific function of these hippocampal subregions in reversal learning.     

Environmental novelty is associated with a selective increase in Fos expression in the output elements of the hippocampal formation and the perirhinal cortex

If the hippocampus plays a role in the detection of novel environmental features, then novelty should be associated with altered hippocampal neural activity and perhaps also measures of neuroplasticity. We examined Fos protein expression within subregions of rat hippocampal formation as an indicator of recent increases in neuronal excitation and cellular processes that support neuroplasticity. Environmental novelty, but not environmental complexity, led to a selective increase of Fos induction in the final “output” subregion of the dorsal hippocampal trisynaptic circuit (CA1) and a primary projection site (layer five of the lateral entorhinal cortex, ERC), as well as in the perirhinal cortex. There was no selective effect of novelty on Fos expression within “input” elements of the trisynaptic circuit (ERC layer two, the dentate gyrus or CA3) or other comparison brain regions that may be responsive to overall motor-sensory activity or anxiety levels (primary somatosensory and motor cortex or hypothalamic paraventricular nucleus). Test session ambulatory behavior increased with both novelty and environmental complexity and was not significantly correlated with Fos expression patterns in any of the brain regions examined. In contrast, the extent of manipulated environmental novelty was strongly correlated with Fos expression in CA1. These results support the prospect that a novelty-associated signal is generated within hippocampal neurocircuitry, is relayed to cortical projection sites, and specifically up-regulates neuroplasticity-supporting processes with dorsal hippocampal CA1 and ERC layer five. Whether novelty-dependent Fos induction in perirhinal cortex depends on this hippocampal output or reflects an independent process remains to be determined.The hippocampus appears to play an essential role in the encoding of configural and temporal relationships between experiential elements thereby supporting memory for environmental contexts and discrete episodes (Rudy and Sutherland 1995). A related hypothesis is that the hippocampus serves as a functional comparator of present and past (stored) experience, and consequently directs attention and mnemonic processes to the novel aspects of present experience (Margulies 1985; Otto and Eichenbaum 1992; Knight 1996; Mizumori et al. 1999; Moser and Paulsen 2001; Vinogradova 2001; Fyhn et al. 2002; Norman and O''Reilly 2003). A comparator capability of the hippocampus seems plausible given the converging parallel neural pathways by which multimodal sensory information is presented to the hippocampus. The entorhinal cortex serves as an anatomical gateway through which the majority of cortically processed information is presented to the hippocampus. This cortical information is relayed directly (via monosynaptic connections) to CA1 neurons (originating primarily from layer three of the entorhinal cortex) or to CA3 neurons (originating primarily from layer two of the entorhinal cortex) (Steward and Scoville 1976; Remondes and Schuman 2004; Witter and Amaral 2004). In addition, CA1 neurons are presented with cortical information (originating primarily from layer two of the entorhinal cortex) that has first been processed by the dentate gyrus and CA3, via the serial connections of the hippocampal formation trisynaptic circuit (Andersen et al. 1971). Although both CA1 and CA3 neurons receive direct and indirect neural input from entorhinal cortex, several hippocampal-circuit models propose that CA1 neurons have unique access to both past (stored) and ongoing experiential neural patterns (Hasselmo and Schnell 1994; Moser and Paulsen 2001; Norman and O''Reilly 2003). Alternatively, other models posit an important role of CA3 neurons (Mizumori et al. 1999; Vinogradova 2001; Lee et al. 2005a) and/or dentate gyrus granule cells (Meeter et al. 2004; Lee et al. 2005a) in the detection of novel features of experience.Implicit in these models of hippocampal function is the assumption that the hippocampus is engaged differently when presented with novel versus familiar stimuli patterns. There is some evidence for experience-dependent differences in rodent hippocampal activity that are manifest by electrophysiological differences in individual or ensemble neuronal activity patterns (Otto and Eichenbaum 1992; Fyhn et al. 2002; Nitz and McNaughton 2004). Neuroimaging studies in humans have detected increased fMRI activity in the hippocampal region during encoding of novel visual stimuli (Stern et al. 1996; Johnson et al. 2008). Moreover, humans with hippocampal damage exhibit altered event-related potentials in response to novel stimuli (Knight 1996).Hippocampal activity that varies with the novelty of an experience may be important for guiding ongoing behavior (e.g., exploratory behavior and vigilance), and if so, should also produce detectable differences in activity of hippocampal efferents. In addition, detection of novelty may be important for altering neuroplastic processes within components of the hippocampus. The goal of our study was to examine across hippocampal formation subregions the levels of a cellular marker of neural activity and neuroplasticity (Fos expression) associated with environmental experiences that vary in novelty and complexity. The expression of the protein product, Fos, of the immediate early gene, c-fos, may be a good molecular indicator of recent increases in general molecular changes that contribute to neuroplasticity. Expression of Fos reflects an intracellular state of cells that varies primarily as a result of recent activation by intercellular signals (e.g., neurotransmitters, hormones, paracrine factors, and adhesion molecules) (Herdegen and Leah 1998). Hippocampal Fos expression is associated with recent increases in neuronal firing, although apparently in a complex fashion (Labiner et al. 1993). Increases in hippocampal Fos is also believed to be an important mediator of activity-dependent neuroplasticity (Sheng and Greenberg 1990).In our study we examined the number of Fos immunopositive cells in the dentate gyrus, subregions of the hippocampus (CA1, CA2, CA3, and CA4), and layers two and five of the lateral entorhinal cortex. In addition, we examined Fos immunoreactivity in the perirhinal cortex. There is accumulating support for this brain region to play a role in the detection of novel stimuli in a configuration independent manner (Brown and Aggleton 2001; Kumaran and Maguire 2007). For comparison purposes, we also examined Fos expression patterns in primary somatosensory cortex, primary motor cortex, and the hypothalamic paraventricular nucleus (PVN). Fos expression levels in the somatosensory and motor cortex may reflect the varying amounts of somatosensation and motor activity present during the experimental test-day experiences. Fos expression levels in the PVN may reflect the varying amounts of test-day stress and anxiety associated with the different treatment conditions.Several other rat studies have examined the relationship between stimuli novelty (e.g., visual images, extramaze environmental cues, or new learning tasks) and Fos expression in the hippocampus (Hess et al. 1995a; Wan et al. 1999; Vann et al. 2000). Whereas those other studies utilized tasks that had a training phase and operant reward component, our study examined Fos expression in rats placed in a novel or familiar environment with no training components or operant contingencies. The pattern of Fos expression associated with unrewarded exploratory behavior may better reflect the extent to which novelty and complexity differentially and automatically engage the hippocampus than does the pattern of Fos expression associated with various learning regimens and their particular task demands (Kumaran and Maguire 2007).     

Hippocampal structure and human cognition: Key role of spatial processing and evidence supporting the efficiency hypothesis in females

Here we apply a method for automated segmentation of the hippocampus in 3D high-resolution structural brain MRI scans. One hundred and four healthy young adults completed twenty one tasks measuring abstract, verbal, and spatial intelligence, along with working memory, executive control, attention, and processing speed. After permutation tests corrected for multiple comparisons across vertices (p < .05), significant relationships were found for spatial intelligence, spatial working memory, and spatial executive control. Interactions with sex revealed significant relationships with the general factor of intelligence (g), along with abstract and spatial intelligence. These correlations were mainly positive for males but negative for females, which might support the efficiency hypothesis in women. Verbal intelligence, attention, and processing speed were not related to hippocampal structural differences.     

Corticosterone effects on BDNF mRNA expression in the rat hippocampus during morris water maze training

Corticosterone and Brain-Derived Neurotrophic Factor (BDNF) have both been shown to be involved in spatial memory formation in rats. In the present study we have investigated the effect of corticosterone on hippocampal BDNF mRNA expression after training in the Morris water maze in young adult Wistar rats. Therefore, we first studied BDNF mRNA levels in the hippocampus in relation to corticosterone levels at several time points after 4 training trials in the Morris water maze. Corticosterone levels were significantly increased after this procedure, and hippocampal BDNF mRNA levels only displayed a minor change: an increase in CA1 at 1 hr after training. However, in a previous study we observed dramatically decreased hippocampal BDNF mRNA levels in dentate gyrus and CA1 at 3 hr after injection of corticosterone. In order to analyze this discrepancy, we subsequently investigated if hippocampal BDNF mRNA expression is affected by corticosterone at 3 hr after water maze training. Therefore, we incorporated ADX animals and ADX animals which were injected with corticosterone in our study. ADX animals which were subjected to water maze training displayed similar hippocampal BDNF mRNA levels 3 hr after training compared to control ADX animals. Furthermore, ADX animals which were injected with corticosterone showed decreased BDNF mRNA levels in all hippocampal regions compared to control ADX animals. Water maze training did not alter this effect. Thus, the increased corticosterone levels during water maze training do not affect hippocampal BDNF mRNA expression, although exogenous corticosterone is effective under these conditions. Hence, our results suggest that in this situation BDNF is resistant to regulation by endogenous corticosterone, which may be important for learning and memory processes.     

Microinjections of leupeptin in the frontal cortex or dorsal hippocampus block spatial learning in the rat

Adult male Long-Evans hooded rats were given bilateral microinjections of 18 mM leupeptin or saline through cannulae implanted with tips aimed at the frontal cortex or CA1 or CA3 hippocampal cell fields. Five minutes following injections animals were allowed to complete an eight-arm radial maze. The acquisition criterion required that the animal make 7 correct choices of the first 8, and 8 correct choices of the first 10, for five consecutive sessions. Leupeptin slowed acquisition of the eight-arm radial maze task when injected into the CA1 and CA3 hippocampal fields or the frontal cortex, but did not influence spontaneous activity. These results suggest that earlier reports of the amnestic effect of leupeptin when administered into the lateral cerebral ventricle may have been due to effects within the cortex and hippocampus. The present experiment represents the first attempt to identify behaviorally those brain areas in which leupeptin acts to alter learning.     

Posterior parietal cortex as part of a neural network for directed attention in rats

A rodent model of directed attention has been developed based upon behavioral analysis of contralateral neglect, pharmacological manipulations, and anatomical analysis of neural circuitry. In each of these three domains the rodent model exhibits striking similarities to humans. We hypothesize that there is a specific thalamo-cortical-basal ganglia network that subserves spatial attentional functions. Key components of this network are medial agranular and posterior parietal cortex, dorsocentral striatum, and the lateral posterior thalamic nucleus. Several issues need to be addressed before we can hope to realistically understand or model the functions of this network. Among these are the roles of medial versus lateral posterior parietal cortex; cholinergic mechanisms in attention; interhemispheric interactions; the role of synchronous firing at the cortical, striatal, and thalamic levels; interactions between cortical and thalamic projections to the striatum; interactions between cortical and nigral inputs to the thalamus; the role of collicular inputs to the lateral posterior thalamic nucleus; the role of cerebral cortex versus superior colliculus in driving the motor output expressed as orienting behavior during directed attention; the extent to which the circuitry we describe for directed attention also plays a role in other forms of attention.     

Effects of motor-cognitive coordination training and cardiovascular training on motor coordination and cognitive functions

ObjectivesNumerous recent studies showed that physical training can enhance cognitive abilities, such as attention, spatial ability, memory performance, and executive functions. However, most of these studies focused on the efficiency of cardiovascular training, whereas evidence for combined motor-cognitive training emphasizing coordination abilities is scarce. Therefore, the aim of the present study was to investigate the effects of motor-cognitive coordination training and moderate cardiovascular training on cognitive functions and to test whether these effects were related to participant's fitness level.Design and methodWe tested 50 physically active (mean age = 23.5 years, SD = 3.2) and 56 sedentary participants (mean age = 23.4 years, SD = 3.2) in a pretest-training-posttest design with 12 sessions of moderate cardiovascular training (≈60% HRmax) or motor-cognitive coordination training. The training groups were compared to a passive control group. At pretest and posttest, participants performed an untrained motor-cognitive coordination task, measures of executive control (cognitive flexibility, inhibition, working memory), spatial ability, and fluid intelligence.Results and conclusionsWe found improved coordination abilities in the coordination training group, but no transfer of training to cognitive measures in physically active participants. However, sedentary participants showed larger improvements in terms of inhibition in the coordination training group compared to the remaining groups, while the cardiovascular training group improved in cognitive flexibility compared to the remaining groups. In sum, there are positive but differential effects of cardiovascular training and coordination training on cognitive performance in sedentary young participants, suggesting that coordination training may be a useful intervention especially for individuals that cannot perform cardiovascular training.     

Hippocampal CA1 spiking during encoding and retrieval: relation to theta phase

The hippocampal theta rhythm is a prominent oscillation in the field potential observed throughout the hippocampus as a rat investigates stimuli in the environment. A recent computational model [Hasselmo, M. E., Bodelon, C., & Wyble, B. P. (2002a). A proposed function for hippocampal theta rhythm: separate phases of encoding and retrieval enhance reversal of prior learning. Neural Computation, 14, 793-817. Neuromodulation, theta rhythm and rat spatial navigation. Neural Networks, 15, 689-707] suggested that the theta rhythm allows the hippocampal formation to alternate rapidly between conditions that promote memory encoding (strong synaptic input from entorhinal cortex to areas CA3 and CA1) and conditions that promote memory retrieval (strong synaptic input from CA3 to CA1). That model predicted that the preferred theta phase of CA1 spiking should differ for information being encoded versus information being retrieved. In the present study, the spiking activity of CA1 pyramidal cells was recorded while rats performed either an odor-cued delayed nonmatch-to-sample recognition memory test or an object recognition memory task based on the animal's spontaneous preference for novelty. In the test period of both tasks, the preferred theta phase exhibited by CA1 pyramidal cells differed between moments when the rat inspected repeated (match) and non-repeated (nonmatch) items. Also in the present study, additional modeling work extended the previous model to address the mean phase of CA1 spiking associated with stimuli inducing varying levels of retrieval relative to encoding, ranging from novel nonmatch stimuli with no retrieval to highly familiar repeated stimuli with extensive retrieval. The modeling results obtained here demonstrated that the experimentally observed phase differences are consistent with different levels of CA3 synaptic input to CA1 during recognition of repeated items.     

Sex differences in spatial and non-spatial Y-maze performance after chronic stress

Chronic restraint is known to alter hippocampal CA3 dendritic morphology and spatial memory in male rats. The present study examined whether female rats, which exhibit different anatomical adaptations to chronic stress than those of males, would also show spatial memory impairments. Male and female Sprague-Dawley rats were restrained for 6 h/day for 21 days, a time frame previously demonstrated to cause hippocampal CA3 dendritic atrophy. The day after the last restraint session, rats were tested on a Y-maze, a habituation task that can be used to assess spatial memory. Chronic stress impaired Y-maze performance in both sexes without affecting levels of locomotion as measured by total arm entries in the first minute. However, Y-maze performance of stressed females improved in 2-5 min when chronically stressed males continued to show poor Y-maze performance. The enhanced Y-maze performance of chronically stressed females occurred when total arm entries were higher compared to the entries made by males. Therefore, correlations were performed between total arm entries and spatial memory in 1 and 2-5 min. In the first minute when control females demonstrated functional spatial memory, female controls with the lowest locomotor levels exhibited the best performance. The correlations for stressed females were not significant, and neither were the correlations for any group in 2-5 min. Overall, these results show important sex differences in response to chronic stress with females exhibiting an ability to recover quickly from deficits in Y-maze performance.