The medial entorhinal cortex is necessary for the stimulus control over hippocampal place fields by distal, but not proximal, landmarks.

A fundamental property of place cells in the hippocampus is the anchoring of their firing fields to salient landmarks within the environment. However, it is unclear how such information reaches the hippocampus. In the current experiment, we tested the hypothesis that the stimulus control exerted by distal visual landmarks requires input from the medial entorhinal cortex (MEC). Place cells were recorded from mice with ibotenic acid lesions of the MEC (n = 7) and from sham-lesioned mice (n = 6) following 90° rotations of either distal landmarks or proximal cues in a cue- controlled environment. We found that lesions of the MEC impaired the anchoring of place fields to distal landmarks, but not proximal cues. We also observed that, relative to sham-lesioned mice, place cells in animals with MEC lesions exhibited significantly reduced spatial information and increased sparsity. These results support the view that distal landmark information reaches the hippocampus via the MEC, but that proximal cue information can do so via an alternative neural pathway.

Recapitulation of the EEF1A2 D252H neurodevelopmental disorder-causing missense mutation in mice reveals a toxic gain of function.

Heterozygous de novo mutations in EEF1A2, encoding the tissue-specific translation elongation factor eEF1A2, have been shown to cause neurodevelopmental disorders including often severe epilepsy and intellectual disability. The mutational profile is unusual; ~50 different missense mutations have been identified but no obvious loss of function mutations, though large heterozygous deletions are known to be compatible with life. A key question is whether the heterozygous missense mutations operate through haploinsufficiency or a gain of function mechanism, an important prerequisite for design of therapeutic strategies. In order both to address this question and to provide a novel model for neurodevelopmental disorders resulting from mutations in EEF1A2, we created a new mouse model of the D252H mutation. This mutation causes the eEF1A2 protein to be expressed at lower levels in brain but higher in muscle in the mice. We compared both heterozygous and homozygous D252H and null mutant mice using behavioural and motor phenotyping alongside molecular modelling and analysis of binding partners. Although the proteomic analysis pointed to a loss of function for the D252H mutant protein, the D252H homozygous mice were more severely affected than null homozygotes on the same genetic background. Mice that are heterozygous for the missense mutation show no behavioural abnormalities but do have sex-specific deficits in body mass and motor function. The phenotyping of our novel mouse lines, together with analysis of molecular modelling and interacting proteins, suggest that the D252H mutation results in a gain of function.

Lateral entorhinal cortex lesions impair odor-context associative memory in male rats.

Lateral entorhinal cortex (LEC) has been hypothesized to process nonspatial, item information that is combined with spatial information from medial entorhinal cortex to form episodic memories within the hippocampus. Recent studies, however, have demonstrated that LEC has a role in integrating features of episodic memory prior to the hippocampus. While the precise role of LEC is still unclear, anatomical studies show that LEC is ideally placed to be a hub integrating multisensory information. The current study tests whether the role of LEC in integrating information extends to long-term multimodal item-context associations. In Experiment 1, male rats were trained on a context-dependent odor discrimination task, where two different contexts served as the cue to the correct odor. Rats were pretrained on the task and then received either bilateral excitotoxic LEC or sham lesions. Following surgery, rats were tested on the previously learned odor-context associations. Control rats showed good memory for the previously learned association but rats with LEC lesions showed significantly impaired performance relative to both their own presurgery performance and to control rats. Experiment 2 went on to test whether impairments in Experiment 1 were the result of LEC lesions impairing either odor or context memory retention alone. Male rats were trained on simple odor and context discrimination tasks that did not require integration of features to solve. Following surgery, both LEC and control rats showed good memory for previously learned odors and contexts. These data show that LEC is critical for long-term odor-context associative memory.

Social dominance and rainfall predict telomere dynamics in a cooperative arid-zone bird.

In many vertebrate societies dominant individuals breed at substantially higher rates than subordinates, but whether this hastens ageing remains poorly understood. While frequent reproduction may trade off against somatic maintenance, the extraordinary fecundity and longevity of some social insect queens highlight that breeders need not always suffer more rapid somatic deterioration than their nonbreeding subordinates. Here, we used extensive longitudinal assessments of telomere dynamics to investigate the impact of dominance status on within-individual age-related changes in somatic integrity in a wild social bird, the white-browed sparrow-weaver (Plocepasser mahali). Dominant birds, who monopolise reproduction, had neither shorter telomeres nor faster telomere attrition rates over the long-term (1-5 years) than their subordinates. However, over shorter (half-year) time intervals dominants with shorter telomeres showed lower rates of telomere attrition (and evidence suggestive of telomere lengthening), while the same was not true among subordinates. Dominants may therefore invest more heavily in telomere length regulation (and/or somatic maintenance more broadly); a strategy that could mitigate the long-term costs of reproductive effort, leaving their long-term telomere dynamics comparable to those of subordinates. Consistent with the expectation that reproduction entails short-term costs to somatic integrity, telomere attrition rates were most severe for all birds during the breeding seasons of wetter years (rainfall is the key driver of reproductive activity in this arid-zone species). Our findings suggest that, even in vertebrate societies in which dominants monopolise reproduction, dominants may experience long-term somatic integrity trajectories indistinguishable from those of their nonreproductive subordinates.

Antiepileptic drugs for the primary and secondary prevention of seizures after stroke.

BACKGROUND: Seizures after stroke are an important clinical problem and may result in poor outcomes. The indications of antiepileptic drugs (AEDs) for seizure prophylaxis after stroke remain unclear. This is an updated version of the Cochrane Review previously published in 2014. OBJECTIVES: To assess the effects of AEDs for the primary and secondary prevention of seizures after stroke. For primary prevention, we aimed to assess whether AEDs reduce the likelihood of seizures in people who have a stroke but do not have a seizure. For secondary prevention, we aimed to assess whether AEDs reduce the likelihood of further seizures in people who have a stroke and at least one post-stroke seizure. SEARCH METHODS: We searched the following databases on 9 March 2021: Cochrane Register of Studies (CRS Web), MEDLINE (Ovid, 1946 to March 08, 2021). CRS Web includes randomised or quasi-randomised controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organisation International Clinical Trials Registry Platform (ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the Specialised Registers of Cochrane Review Groups including Epilepsy and Stroke. We also checked the reference lists of articles retrieved from these searches. SELECTION CRITERIA: We selected randomised and quasi-randomised controlled studies that recruited participants with a clinical diagnosis of stroke, either ischaemic or haemorrhagic. We excluded studies that only recruited participants with subarachnoid haemorrhage, subdural haemorrhage, extradural haemorrhage, or other non-stroke diagnoses such as tumour- or infection-related infarction or haemorrhage. We also excluded studies that recruited only participants who had undergone neurosurgery. We included participants of all ages suffering any seizure type who were assigned to AEDs or placebo groups. DATA COLLECTION AND ANALYSIS: In accordance with standard methodological procedures expected by The Cochrane Collaboration, two review authors independently assessed trials for inclusion before evaluating trial risk of bias and extracting relevant data. The primary outcome assessed was the proportion of participants who experienced seizures in the follow-up period. We presented results as summary risk ratios (RRs) with 95% confidence intervals (CIs) for dichotomous outcomes and mean differences (MDs) with 95% CIs for continuous outcomes. Where we had sufficient data, we calculated random-effects (Mantel-Haenszel) meta-analyses for dichotomous outcomes; otherwise, we reported results narratively. We used the I2 statistic to analyse statistical heterogeneity. We planned to use funnel plots to assess publication bias in meta-analyses with at least 10 included studies. We used the GRADE approach to assess the certainty of the evidence. MAIN RESULTS: Two studies with a total of 856 subjects were included. AEDs were not shown to be effective in primary prophylaxis of post-stroke seizure (RR 0.65, 95% CI 0.34 to 1.26; 2 studies, 856 participants; moderate-certainty evidence). The first study was a randomised double-blind study comparing valproic acid with placebo for primary seizure prevention up to one year after stroke. The study included 72 adults with intracerebral haemorrhage. There was no difference in the risk of post-stroke seizures (RR 0.88, 95% CI 0.35 to 2.16) or of death (RR 1.20, 95% CI 0.40 to 3.58). The second study was a substudy on the use of diazepam in acute stroke. It was a randomised double-blind study, comparing a three-day diazepam treatment versus placebo for primary seizure prevention up to three months after stroke in 784 adults with acute stroke. There was no evidence of a difference in the risk of post-stroke seizures for all stroke or subgroups of haemorrhagic or ischaemic stroke (RR for all stroke 0.47, 95% CI 0.18 to 1.22). In a subgroup analysis of anterior circulation cortical infarcts, primary prophylaxis with diazepam was associated with a reduced risk of post-stroke seizures (RR 0.21, 95% CI 0.05 to 0.95). Risks of mortality did not differ between the diazepam and the placebo group at two weeks (RR 0.84, 95% CI 0.56 to 1.26) and three months follow-up (RR 0.95, 95% CI 0.72 to 1.26). We assessed both studies to be at a low overall risk of bias. Using the GRADE approach, we assessed the overall certainty of the evidence as low to moderate. AUTHORS' CONCLUSIONS: There is insufficient evidence to support the routine use of AEDs on the primary and secondary prevention of seizures after stroke. Further well-conducted studies are warranted for this important clinical problem.

The Black Box effect: sensory stimulation after learning interferes with the retention of long-term object location memory in rats.

Reducing sensory experiences during the period that immediately follows learning improves long-term memory retention in healthy humans, and even preserves memory in patients with amnesia. To date, it is entirely unclear why this is the case, and identifying the neurobiological mechanisms underpinning this effect requires suitable animal models, which are currently lacking. Here, we describe a straightforward experimental procedure in rats that future studies can use to directly address this issue. Using this method, we replicated the central findings on quiet wakefulness obtained in humans: We show that rats that spent 1 h alone in a familiar dark and quiet chamber (the Black Box) after exploring two objects in an open field expressed long-term memory for the object locations 6 h later, while rats that instead directly went back into their home cage with their cage mates did not. We discovered that both visual stimulation and being together with conspecifics contributed to the memory loss in the home cage, as exposing rats either to light or to a cage mate in the Black Box was sufficient to disrupt memory for object locations. Our results suggest that in both rats and humans, everyday sensory experiences that normally follow learning in natural settings can interfere with processes that promote long-term memory retention, thereby causing forgetting in form of retroactive interference. The processes involved in this effect are not sleep-dependent because we prevented sleep in periods of reduced sensory experience. Our findings, which also have implications for research practices, describe a potentially useful method to study the neurobiological mechanisms that might explain why normal sensory processing after learning impairs memory both in healthy humans and in patients suffering from amnesia.

Longitudinal evidence that older parents produce offspring with longer telomeres in a wild social bird.

As telomere length (TL) often predicts survival and lifespan, there is considerable interest in the origins of inter-individual variation in TL. Cross-generational effects of parental age on offspring TL are thought to be a key source of variation, but the rarity of longitudinal studies that examine the telomeres of successive offspring born throughout the lives of parents leaves such effects poorly understood. Here, we exploit TL measures of successive offspring produced throughout the long breeding tenures of parents in wild white-browed sparrow weaver (Plocepasser mahali) societies, to isolate the effects of within-parent changes in age on offspring TLs. Our analyses reveal the first evidence to date of a positive within-parent effect of advancing age on offspring TL: as individual parents age, they produce offspring with longer telomeres (a modest effect that persists into offspring adulthood). We consider the potential for pre- and post-natal mechanisms to explain our findings. As telomere attrition predicts offspring survival to adulthood in this species, this positive parental age effect could impact parent and offspring fitness if it arose via differential telomere attrition during offspring development. Our findings support the view that cross-generational effects of parental age can be a source of inter-individual variation in TL.

Telomere attrition predicts reduced survival in a wild social bird, but short telomeres do not.

Attempts to understand the causes of variation in senescence trajectories would benefit greatly from biomarkers that reflect the progressive declines in somatic integrity (SI) that lead to senescence. While telomere length has attracted considerable interest in this regard, sources of variation in telomere length potentially unrelated to declines in SI could, in some contexts, leave telomere attrition rates a more effective biomarker than telomere length alone. Here, we investigate whether telomere length and telomere attrition rates predict the survival of wild white-browed sparrow-weaver nestlings (Plocepasser mahali). Our analyses of telomere length reveal counterintuitive patterns: telomere length soon after hatching negatively predicted nestling survival to fledging, a pattern that appears to be driven by differentially high in-nest predation of broods with longer telomeres. Telomere length did not predict survival outside this period: neither hatchling telomere length nor telomere length in the mid-nestling period predicted survival from fledging to adulthood. Our analyses using within-individual telomere attrition rates, by contrast, revealed the expected relationships: nestlings that experienced a higher rate of telomere attrition were less likely to survive to adulthood, regardless of their initial telomere length and independent of effects of body mass. Our findings support the growing use of telomeric traits as biomarkers of SI, but lend strength to the view that longitudinal assessments of within-individual telomere attrition since early life may be a more effective biomarker in some contexts than telomere length alone.

Mental Health Symptoms in Patients With Familial Adenomatous Polyposis: An Observational Study.

BACKGROUND: Almost all patients with familial adenomatous polyposis undergo abdominal surgery with a risk of disease and surgery-related complications. This, the familial nature of the syndrome, and its wide-ranging manifestations make patients prone to mental health symptoms. If this is true, patients need appropriate evaluation and treatment. OBJECTIVE: The purpose of this study was to record the experience of mental health symptoms in a group of unselected patients with FAP. DESIGN: We conducted an observational study using an anonymized mental health symptom survey for patients affected with familial adenomatous polyposis. SETTINGS: The study was conducted using the Hereditary Colorectal Cancer Registry in a tertiary referral center. PATIENTS: Patients affected with familial adenomatous polyposis were included. MAIN OUTCOME MEASURES: Results of the mental health survey were measured. RESULTS: Seventy nine of 100 patients completed the survey; 57 endorsed ≥1 psychosocial symptom (72.2%). with a mean of 4 per patient. Nine patients (11.4%) met all 4 of the American Psychiatric Association diagnostic criteria for posttraumatic stress disorder, and 8 (10.1%) endorsed partial posttraumatic stress disorder criteria (3/4 symptoms). Patients who met all of the criteria for posttraumatic stress disorder had an average of 9.3 psychosocial symptoms each compared with 8.3 for those who met 3 of 4 and 2.2 for those who met <3. Six patients endorsed suicidal thoughts, all of whom met 3 or 4 of the criteria for posttraumatic stress disorder. LIMITATIONS: The study was limited by its referral bias toward severe cases and relatively small number of patients. Because of the limitations of an anonymous self-administered screening, no mental health diagnoses have been given. CONCLUSIONS: Patients with familial adenomatous polyposis are at risk for mental health symptoms, which can be multiple and severe. Some patients need professional counseling. A correlation between familial adenomatous polyposis patients with posttraumatic stress disorder and suicidal ideation is important. See Video Abstract at http://links.lww.com/DCR/A995. SÍNTOMAS PSICOPATOLÓGICOS EN PACIENTES CON PÓLIPOSIS ADENOMATOSO FAMILIAR: UN ESTUDIO OBSERVACIONAL: Un mayoría de pacientes con póliposis adenomatoso familiar (PAF) se someten a cirugía abdominal con los riesgos de enfermedad propria y complicaciones relacionadas a cirugía. Estos factores, la relación familiar del síndrome y sus manifestaciones altamente variables hacen que los pacientes sean propensos a psicopatologías. Si estas consideraciones son validas, los pacientes requieren evaluación y tratamiento adecuado. OBJETIVO: Documentar la experiencia de los síntomas psicopatológicos en un grupo de pacientes no seleccionados con PAF. DISEÑO:: Estudio observacional utilizando una encuesta anónima de síntomas psicopatológicos en pacientes afectados con póliposis adenomatoso familiar. AMBIENTE CLINICO: Registro de cáncer colorrectal hereditario en un centro de referencia de tercer nivel. PACIENTES: Individuos afectados con póliposis adenomatoso familiar. OBJETIVOS PRINCIPALES A VALORACIÓN:: Resultados de la encuesta de salud mental. RESULTADOS: Setenta y nueve de 100 pacientes completaron la encuesta; 57 afirmaron uno o más síntomas psicosociales (72,2%) con un promedio de 4 por paciente. 9 (11,4%) pacientes cumplieron con los 4 criterios de diagnóstico de la Asociación Estadounidense de Psiquiatría para el trastorno por estrés postraumático, y 8 (10,1%) llenaron los criterios del trastorno de estrés postraumático parcial (3/4 síntomas). Los pacientes que cumplieron con todos los criterios para el trastorno por estrés postraumático tuvieron un promedio de 9.3 síntomas psicosociales cada uno, en comparación con 8.3 para los que cumplieron con 3/4 y 2.2 para los que cumplieron con <3. 6 pacientes afirmaron pensamientos de suicidio, todos los cuales cumplieron con 3 o 4 de los criterios para el trastorno por estrés postraumático. LIMITACIONES: Sesgo de referencia hacia casos graves, y un número relativamente pequeño de pacientes. Debido a las limitaciones de un examen anónimo auto administrado, no se confirmaron diagnósticos de psicopatología. CONCLUSIONES: Los pacientes con póliposis adenomatoso familiar tienen riesgo de síntomas de salud mental alterada que pueden ser múltiples y graves. Algunos pacientes necesitan asesoramiento profesional. La correlación entre los pacientes con póliposis adenomatoso familiar con trastorno por estrés postraumático y ideación suicida es importante. Vea el Resumen del Video en http://links.lww.com/DCR/A995.

Field repetition and local mapping in the hippocampus and the medial entorhinal cortex.

Hippocampal place cells support spatial cognition and are thought to form the neural substrate of a global "cognitive map." A widely held view is that parts of the hippocampus also underlie the ability to separate patterns or to provide different neural codes for distinct environments. However, a number of studies have shown that in environments composed of multiple, repeating compartments, place cells and other spatially modulated neurons show the same activity in each local area. This repetition of firing fields may reflect pattern completion and may make it difficult for animals to distinguish similar local environments. In this review we 1) highlight some of the navigation difficulties encountered by humans in repetitive environments, 2) summarize literature demonstrating that place and grid cells represent local and not global space, and 3) attempt to explain the origin of these phenomena. We argue that the repetition of firing fields can be a useful tool for understanding the relationship between grid cells in the entorhinal cortex and place cells in the hippocampus, the spatial inputs shared by these cells, and the propagation of spatially related signals through these structures.

Conserved hippocampal cellular pathophysiology but distinct behavioural deficits in a new rat model of FXS.

Recent advances in techniques for manipulating genomes have allowed the generation of transgenic animals other than mice. These new models enable cross-mammalian comparison of neurological disease from core cellular pathophysiology to circuit and behavioural endophenotypes. Moreover they will enable us to directly test whether common cellular dysfunction or behavioural outcomes of a genetic mutation are more conserved across species. Using a new rat model of Fragile X Syndrome, we report that Fmr1 knockout (KO) rats exhibit elevated basal protein synthesis and an increase in mGluR-dependent long-term depression in CA1 of the hippocampus that is independent of new protein synthesis. These defects in plasticity are accompanied by an increase in dendritic spine density selectively in apical dendrites and subtle changes in dendritic spine morphology of CA1 pyramidal neurons. Behaviourally, Fmr1 KO rats show deficits in hippocampal-dependent, but not hippocampal-independent, forms of associative recognition memory indicating that the loss of fragile X mental retardation protein (FMRP) causes defects in episodic-like memory. In contrast to previous reports from mice, Fmr1 KO rats show no deficits in spatial reference memory reversal learning. One-trial spatial learning in a delayed matching to place water maze task was also not affected by the loss of FMRP in rats. This is the first evidence for conservation across mammalian species of cellular and physiological hippocampal phenotypes associated with the loss of FMRP. Furthermore, while key cellular phenotypes are conserved they manifest in distinct behavioural dysfunction. Finally, our data reveal novel information about the selective role of FMRP in hippocampus-dependent associative memory.

Place field repetition and spatial learning in a multicompartment environment.

Recent studies have shown that place cells in the hippocampus possess firing fields that repeat in physically similar, parallel environments. These results imply that it should be difficult for animals to distinguish parallel environments at a behavioral level. To test this, we trained rats on a novel odor-location task in an environment with four parallel compartments which had previously been shown to yield place field repetition. A second group of animals was trained on the same task, but with the compartments arranged in different directions, an arrangement we hypothesised would yield less place field repetition. Learning of the odor-location task in the parallel compartments was significantly impaired relative to learning in the radially arranged compartments. Fewer animals acquired the full discrimination in the parallel compartments compared to those trained in the radial compartments, and the former also required many more sessions to reach criterion compared to the latter. To confirm that the arrangement of compartments yielded differences in place cell repetition, in a separate group of animals we recorded from CA1 place cells in both environments. We found that CA1 place cells exhibited repeated fields across four parallel local compartments, but did not do so when the same compartments were arranged radially. To confirm that the differences in place field repetition across the parallel and radial compartments depended on their angular arrangement, and not incidental differences in access to an extra-maze visual landmark, we repeated the recordings in a second set of rats in the absence of the orientation landmark. We found, once again, that place fields showed repetition in parallel compartments, and did not do so in radially arranged compartments. Thus place field repetition, or lack thereof, in these compartments was not dependent on extra-maze cues. Together, these results imply that place field repetition constrains spatial learning.

Place fields and the cognitive map.

The discovery of place cells by John O'Keefe in the early 1970s was a breakthrough not just for systems neuroscience, but also for psychology: place fields provided a clear neural substrate for the notion of a cognitive map, a construct devised to explain rat learning and spatial cognition. However, is the robust location-related firing of place cells still best conceptualised as a cognitive map? In this commentary, we reassess this view of hippocampus function in light of subsequent findings on place cells. We argue that as place fields encode local space, and as they are modulated by ongoing behavior, the representation they provide may be more cognitive than map-like.

Hippocampus, delay discounting, and vicarious trial-and-error.

In decision-making, an immediate reward is usually preferred to a delayed reward, even if the latter is larger. We tested whether the hippocampus is necessary for this form of temporal discounting, and for vicarious trial-and-error at the decision point. Rats were trained on a recently developed, adjustable delay-discounting task (Papale et al. (2012) Cogn Affect Behav Neurosci 12:513-526), which featured a choice between a small, nearly immediate reward, and a larger, delayed reward. Rats then received either hippocampus or sham lesions. Animals with hippocampus lesions adjusted the delay for the larger reward to a level similar to that of sham-lesioned animals, suggesting a similar valuation capacity. However, the hippocampus lesion group spent significantly longer investigating the small and large rewards in the first part of the sessions, and were less sensitive to changes in the amount of reward in the large reward maze arm. Both sham- and hippocampus-lesioned rats showed a greater amount of vicarious trial-and-error on trials in which the delay was adjusted. In a nonadjusting version of the delay discounting task, animals with hippocampus lesions showed more variability in their preference for a larger reward that was delayed by 10 s compared with sham-lesioned animals. To verify the lesion behaviorally, rat were subsequently trained on a water maze task, and rats with hippocampus lesions were significantly impaired compared with sham-lesioned animals. The findings on the delay discounting tasks suggest that damage to the hippocampus may impair the detection of reward magnitude.

Prenatal glucocorticoid exposure in rats: programming effects on stress reactivity and cognition in adult offspring.

Human epidemiological studies have provided compelling evidence that prenatal exposure to stress is associated with significantly increased risks of developing psychiatric disorders in adulthood. Exposure to excessive maternal glucocorticoids may underlie this fetal programming effect. In the current study, we assessed how prenatal dexamethasone administration during the last week of gestation affects stress reactivity and cognition in adult offspring. Stress reactivity was assessed by evaluating anxiety-like behavior on an elevated plus maze and in an open field. In addition, to characterize the long-term cognitive outcomes of prenatal exposure to glucocorticoids, animals were assessed on two cognitive tasks, a spatial reference memory task with reversal learning and a delayed matching to position (DMTP) task. Our results suggest that prenatal exposure to dexamethasone had no observable effect on anxiety-like behavior, but affected cognition in the adult offspring. Prenatally dexamethasone-exposed animals showed a transient deficit in the spatial reference memory task and a trend to faster acquisition during the reversal-learning phase. Furthermore, prenatally dexamethasone-treated animals also showed faster learning of new platform positions in the DMTP task. These results suggest that fetal overexposure to glucocorticoids programs a phenotype characterized by cognitive flexibility and adaptability to frequent changes in environmental circumstances. This can be viewed as an attempt to increase the fitness of survival in a potentially hazardous postnatal environment, as predicted by intrauterine adversity. Collectively, our data suggest that prenatal exposure to dexamethasone in rats could be used as an animal model for studying some cognitive components of related psychiatric disorders.

The postsubiculum and spatial learning: the role of postsubicular synaptic activity and synaptic plasticity in hippocampal place cell, object, and object-location memory.

Visual landmarks exert stimulus control over spatial behavior and the spatially tuned firing of place, head-direction, and grid cells in the rodent. However, the neural site of convergence for representations of landmarks and representations of space has yet to be identified. A potential site of plasticity underlying associations with landmarks is the postsubiculum. To test this, we blocked glutamatergic transmission in the rat postsubiculum with CNQX, or NMDA receptor-dependent plasticity with d-AP5. These infusions were sufficient to block evoked potentials from the lateral dorsal thalamus and long-term depression following tetanization of this input to the postsubiculum, respectively. In a second experiment, CNQX disrupted the stability of rat hippocampal place cell fields in a familiar environment. In a novel environment, blockade of plasticity with d-AP5 in the postsubiculum did not block the formation of a stable place field map following a 6 h delay. In a final behavioral experiment, postsubicular infusions of both compounds blocked object-location memory in the rat, but did not affect object recognition memory. These results suggest that the postsubiculum is necessary for the recognition of familiar environments, and that NMDA receptor-dependent plasticity in the postsubiculum is required for the formation of new object-place associations that support recognition memory. However, plasticity in the postsubiculum is not necessary for the formation of new spatial maps.

Prepubertal stress and hippocampal function: sex-specific effects.

The chances of developing psychiatric disorders in adulthood are increased when stress is experienced early in life. In particular, stress experienced in the childhood or 'prepubertal' phase is associated with the later development of disorders such as depression, anxiety, post-traumatic stress disorder, and psychosis. Relatively little is known about the biological basis of this effect, but one hypothesis is that prepubertal stress produces long-lasting changes in brain development, particularly in stress sensitive regions such as the hippocampus, leaving an individual vulnerable to disorders in adulthood. In this study, we used an animal model of prepubertal stress to investigate the hypothesis that prepubertal stress induces alterations in hippocampal function in adulthood. Male and female rats were exposed to a brief, variable prepubertal stress protocol (postnatal days 25-27), and their performance in two distinct hippocampal-dependent tasks (contextual fear and spatial navigation) was compared with controls in adulthood. Prepubertal stress significantly impaired contextual fear responses in males and enhanced performance in spatial navigation in females. These results demonstrate that exposure to a brief period of stress in the prepubertal phase alters hippocampal-dependent behaviors in adulthood in a sex-specific manner.

Antiepileptic drugs for the primary and secondary prevention of seizures after stroke.

BACKGROUND: This is an updated version of the original Cochrane review published in 2010, Issue 1. Seizures after stroke are an important clinical problem, and they may be associated with poor outcome. The effects of antiepileptic drugs for the primary and secondary prevention of seizures after stroke remain unclear. OBJECTIVES: We aimed to assess the effects of antiepileptic drugs for the primary and secondary prevention of seizures after stroke. SEARCH METHODS: We searched the Specialised Registers of the Cochrane Epilepsy Group (12 August 2013) and the Cochrane Stroke Group (12 August 2013), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2013, Issue 7), and MEDLINE (OVID, 1946 to 12 August 2013). We also checked the reference lists of articles retrieved from these searches. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials in which participants were assigned to treatment or control group (placebo or no drug). DATA COLLECTION AND ANALYSIS: Two review authors independently screened all the titles, abstracts, and keywords of publications identified by the searches to assess their eligibility, and both review authors assessed their suitability for inclusion according to prespecified selection criteria. We included only one study for data collection and analysis. MAIN RESULTS: We found only one trial that fulfilled the study inclusion criteria of comparison of the effects of an antiepileptic drug with placebo (or no drug) for the primary or secondary prevention of seizures after stroke. This was a prospective randomised, double-blind, placebo-controlled trial comparing valproic acid with placebo for primary prevention of seizures in 72 adults (over 18 years of age) with spontaneous non-aneurysmal, non-traumatic intracerebral haemorrhage; no statistically significant difference in outcome (seizure occurrence at one year) was demonstrated between groups. AUTHORS' CONCLUSIONS: Currently, there is insufficient evidence to support the routine use of antiepileptic drugs for the primary or secondary prevention of seizures after stroke. Further well-conducted research is needed for this important clinical problem.

Local origin of excitatory-inhibitory tuning equivalence in a cortical network.

The interplay between excitation and inhibition determines the fidelity of cortical representations. The receptive fields of excitatory neurons are often finely tuned to encoded features, but the principles governing the tuning of inhibitory neurons remain elusive. In this study, we recorded populations of neurons in the mouse postsubiculum (PoSub), where the majority of excitatory neurons are head-direction (HD) cells. We show that the tuning of fast-spiking (FS) cells, the largest class of cortical inhibitory neurons, was broad and frequently radially symmetrical. By decomposing tuning curves using the Fourier transform, we identified an equivalence in tuning between PoSub-FS and PoSub-HD cell populations. Furthermore, recordings, optogenetic manipulations of upstream thalamic populations and computational modeling provide evidence that the tuning of PoSub-FS cells has a local origin. These findings support the notion that the equivalence of neuronal tuning between excitatory and inhibitory cell populations is an intrinsic property of local cortical networks.