Neural Correlates of Spatial Navigation in Primate Hippocampus / 神经科学通报·英文版

The hippocampus has been extensively implicated in spatial navigation in rodents and more recently in bats. Numerous studies have revealed that various kinds of spatial information are encoded across hippocampal regions. In contrast, investigations of spatial behavioral correlates in the primate hippocampus are scarce and have been mostly limited to head-restrained subjects during virtual navigation. However, recent advances made in freely-moving primates suggest marked differences in spatial representations from rodents, albeit some similarities. Here, we review empirical studies examining the neural correlates of spatial navigation in the primate (including human) hippocampus at the levels of local field potentials and single units. The lower frequency theta oscillations are often intermittent. Single neuron responses are highly mixed and task-dependent. We also discuss neuronal selectivity in the eye and head coordinates. Finally, we propose that future studies should focus on investigating both intrinsic and extrinsic population activity and examining spatial coding properties in large-scale hippocampal-neocortical networks across tasks.

Contextual Fear Learning and Extinction in the Primary Visual Cortex of Mice / 神经科学通报·英文版

Fear memory contextualization is critical for selecting adaptive behavior to survive. Contextual fear conditioning (CFC) is a classical model for elucidating related underlying neuronal circuits. The primary visual cortex (V1) is the primary cortical region for contextual visual inputs, but its role in CFC is poorly understood. Here, our experiments demonstrated that bilateral inactivation of V1 in mice impaired CFC retrieval, and both CFC learning and extinction increased the turnover rate of axonal boutons in V1. The frequency of neuronal Ca2+ activity decreased after CFC learning, while CFC extinction reversed the decrease and raised it to the naïve level. Contrary to control mice, the frequency of neuronal Ca2+ activity increased after CFC learning in microglia-depleted mice and was maintained after CFC extinction, indicating that microglial depletion alters CFC learning and the frequency response pattern of extinction-induced Ca2+ activity. These findings reveal a critical role of microglia in neocortical information processing in V1, and suggest potential approaches for cellular-based manipulation of acquired fear memory.

Hippocampus: Molecular, Cellular, and Circuit Features in Anxiety / 神经科学通报·英文版

Anxiety disorders are currently a major psychiatric and social problem, the mechanisms of which have been only partially elucidated. The hippocampus serves as a major target of stress mediators and is closely related to anxiety modulation. Yet so far, its complex anatomy has been a challenge for research on the mechanisms of anxiety regulation. Recent advances in imaging, virus tracking, and optogenetics/chemogenetics have permitted elucidation of the activity, connectivity, and function of specific cell types within the hippocampus and its connected brain regions, providing mechanistic insights into the elaborate organization of the hippocampal circuitry underlying anxiety. Studies of hippocampal neurotransmitter systems, including glutamatergic, GABAergic, cholinergic, dopaminergic, and serotonergic systems, have contributed to the interpretation of the underlying neural mechanisms of anxiety. Neuropeptides and neuroinflammatory factors are also involved in anxiety modulation. This review comprehensively summarizes the hippocampal mechanisms associated with anxiety modulation, based on molecular, cellular, and circuit properties, to provide tailored targets for future anxiety treatment.

Entrainment of Astrocytic and Neuronal Ca2+ Population Dynamics During Information Processing of Working Memory in Mice / 神经科学通报·英文版

Astrocytes are increasingly recognized to play an active role in learning and memory, but whether neural inputs can trigger event-specific astrocytic Ca2+ dynamics in real time to participate in working memory remains unclear due to the difficulties in directly monitoring astrocytic Ca2+ dynamics in animals performing tasks. Here, using fiber photometry, we showed that population astrocytic Ca2+ dynamics in the hippocampus were gated by sensory inputs (centered at the turning point of the T-maze) and modified by the reward delivery during the encoding and retrieval phases. Notably, there was a strong inter-locked and antagonistic relationship between the astrocytic and neuronal Ca2+ dynamics with a 3-s phase difference. Furthermore, there was a robust synchronization of astrocytic Ca2+ at the population level among the hippocampus, medial prefrontal cortex, and striatum. The inter-locked, bidirectional communication between astrocytes and neurons at the population level may contribute to the modulation of information processing in working memory.

Difference of brain-derived neurotrophic factor expression and pyramid cell count during mastication of food with varying hardness

Abstract Previous studies suggested that mastication activity can affect learning and memory function. However, most were focused on mastication impaired models by providing long-term soft diet. The effects of chewing food with various hardness, especially during the growth period, remain unknown. Objective: To analyze the difference of hippocampus function and morphology, as characterized by pyramidal cell count and BDNF expression in different mastication activities. Materials and Methods: 28-day old, post-weaned, male-Wistar rats were randomly divided into three groups (n=7); the first (K0) was fed a standard diet using pellets as the control, the second (K1) was fed soft food and the third (K2) was fed hard food. After eight weeks, the rats were decapitated, their brains were removed and placed on histological plates made to count the pyramid cells and quantify BDNF expression in the hippocampus. Data collected were compared using one-way ANOVA. Results: Results confirmed the pyramid cell count (K0=169.14±27.25; K1=130.14±29.32; K2=128.14±39.02) and BDNF expression (K0=85.27±19.78; K1=49.57±20.90; K2=36.86±28.97) of the K0 group to be significantly higher than that of K1 and K2 groups (p<0.05); no significant difference in the pyramidal cell count and BNDF expression was found between K1 and K2 groups (p>0.05). Conclusion: A standard diet leads to the optimum effect on hippocampus morphology. Food consistency must be appropriately suited to each development stage, in this case, hippocampus development in post-weaned period.

Effect of intra-hippocampal injection of human recombinant growth hormone on synaptic plasticity in the nucleus basalis magnocellularis-lesioned aged rats / Efeito da injeção intrahipocampal de hormônio do crescimento humano recombinante sobre a plasticidade sináptica em ratos envelhecidos lesados do núcleo basalis magnocellularis

ABSTRACT In this study, we proposed that administration of hippocampal growth hormone in ageing animals with growth hormone deficiency can compensate long-term potentiation and synaptic plasticity in nucleus basalis magnocellularis (NBM)-lesioned rats. Aged male Wistar rats were randomly divided into six groups (seven in each) of sham-operated healthy rats (Cont); NBM-lesioned rats (L); NBM-lesioned rats and intrahippocampal injection of growth hormone vehicle (L + Veh); NBM-lesioned and intrahippocampal injection of growth hormone (10, 20 and 40 µg.2 µl-1) (L + GH). In vivo electrophysiological recording techniques were used to characterize maintenance of long-term potentiation at distinct times (1, 2, 3, 24 and 48 hours) after high-frequency stimulation. The population spike was enhanced significantly for about 48 hours following tetanic stimulation in rats treated with a dose-dependent growth hormone compared to the vehicle group (p < 0.05), possibly through neuronal plasticity and neurogenesis in affected areas.

RESUMO Neste estudo, propusemos que a administração de hormônio hipocampal do crescimento em animais envelhecidos com deficiência de hormônio do crescimento pode compensar a potencialização em longo prazo e a plasticidade sináptica em ratos lesados do núcleo basalis magnocellularis (NBM). Ratos machos Wistar foram divididos aleatoriamente em seis grupos (sete ratos em cada grupo) de ratos falso-operados saudáveis (Cont); ratos lesados do NBM (L); ratos lesados do NBM e injeção intrahipocampal de veículo de hormônio do crescimento (L + Veh); ratos lesados do NBM e injeção de hormônio do crescimento (10, 20 e 40 μg.2 μl-1) (L + GH). Técnicas de registro eletrofisiológico in vivo foram utilizadas para caracterizar a manutenção da potencialização em longo prazo em momentos distintos (1, 2, 3, 24 e 48 horas) após estimulação de alta frequência. O pico populacional aumentou significativamente cerca de 48 horas após a estimulação tetânica em ratos tratados com um hormônio do crescimento dose-dependente, em comparação com o grupo veículo (p <0,05), possivelmente através da plasticidade neuronal e da neogênese nas áreas afetadas.

Absenteísmo-doença no serviço público municipal de Goiânia / Sickness absence in a municipal public service of Goiânia, Brazil

INTRODUÇÃO: O absenteísmo-doença, enquanto falta ao trabalho justificada por licença médica, é um importante indicador das condições de saúde dos trabalhadores. Em geral, características sociodemográficas e ocupacionais situam-se entre os principais fatores associados ao absenteísmo-doença. A administração pública é responsável por 21,8% dos empregos formais no Brasil. Esta população permite o estudo de uma grande variedade de categorias profissionais. OBJETIVO: Analisar o perfil e os indicadores de absenteísmo-doença entre servidores municipais de Goiânia, no Estado de Goiás, Brasil. Métodos: Estudo transversal das licenças certificadas para tratamento de saúde superiores a três dias, de todos os servidores, desde janeiro de 2005 a dezembro de 2010. Foram calculadas as prevalências, utilizando como critérios o número de indivíduos, os episódios e os dias de afastamento. RESULTADOS: Foram concedidas 40.578 licenças certificadas para tratamento de saúde a 13.408 servidores numa população média anual de 17.270 pessoas, o que resultou em 944.722 dias de absenteísmo. A prevalência acumulada de licença no período foi de 143,7%, com média anual de 39,2% e duração de 23 dias por episódio. A prevalência acumulada de absenteísmo-doença foi maior entre mulheres (52,0%) com idade superior a 40 anos (55,9%), com companheiro (49,9%), de baixa escolaridade (54,4%), profissionais de educação (54,7%), > 10 anos de serviço (61,9%) e múltiplos vínculos profissionais (53,7%). Os grupos de diagnósticos (CID-10) com as maiores prevalências acumuladas de licenças foram os do capítulo de transtornos mentais (26,5%), doenças osteomusculares (25,1%) e lesões (23,6%). CONCLUSÕES: Os indicadores de absenteísmo-doença expressam a magnitude desse fenômeno no serviço público e podem auxiliar no planejamento das ações de saúde do trabalhador, priorizando os grupos ocupacionais mais vulneráveis. .

BACKGROUND: Sickness absence, as work absenteeism justified by medical certificate, is an important health status indicator of the employees and, overall, sociodemographic and occupational characteristics are among the main factors associated with sickness absence. Public administration accounts for 21.8% of the formal job positions in Brazil. This population allows the study of a wide range of professional categories. OBJECTIVE: To assess the profile and indicators of sickness absence among public workers from the municipality of Goiania, in the State of Goiás, Brazil. METHODS: A cross-sectional study on certified sick leaves, lasting longer than three days, of all civil servants from January 2005 to December 2010. Prevalence rates were calculated using as main criteria the number of individuals, episodes and sick days. RESULTS: 40,578 certified sick leaves were granted for health treatment among 13,408 public workers, in an annual average population of 17,270 people, which resulted in 944,722 days of absenteeism. The cumulative prevalence of sick leave for the period was of 143.7%, with annual average of 39.2% and duration of 23 days per episode. The cumulative prevalence of sickness absence was higher among women (52.0%), older than 40 years old (55.9%), with a partner (49.9%), low schooling (54.4%), education professionals (54.7%), > 10 years of service (61.9%), and with multiple work contracts (53.7%). Diagnoses groups (ICD-10) with higher cumulative prevalence of sick leaves were those with mental disorders (26.5%), musculoskeletal diseases (25.1%), and injuries (23.6%). CONCLUSIONS: Indicators of sickness absence express the magnitude of this phenomenon in the public sector and can assist in planning health actions for the worker, prioritizing the most vulnerable occupational groups. .

Sensory evaluation of dairy supplements enriched with reduced iron, ferrous sulfate or ferrous fumarate / Evaluación sensorial de suplementos lácteos enriquecidos con hierro reducido, sulfato ferroso o fumarato ferroso

Objective. To determine the degree of liking of the Oportunidades programme dietary supplements (DS) -purees and beverages- added with different iron salts (IS): reduced iron (RI), ferrous sulphate (FS) or ferrous fumarate (FF) during 24 weeks of storage. Materials and methods. The DS were evaluated through a hedonic scale for aroma, flavour and colour attributes; at time zero and every eight weeks, each panel member evaluated three DS with same flavour and presentation but different IS. Seventy women participated as panel members. Results. The chocolate and banana DS exhibited a change in preference by colour and flavour due to storage. DS with FS or RI showed the least preference by flavour and colour in the context of the three IS considered. The chocolate and neutral DS enriched with FS changed their colour and flavour. Conclusion. DS were, in general, well-liked; nonetheless, for purees enriched with FS and for beverages enriched with RI, the less-liked attributes were colour and flavour.

Objetivo. Determinar el nivel de agrado de los suplementos alimenticios (SA) (papillas y bebidas) del Programa Oportunidades, adicionados con diferentes sales de hierro (SH): hierro reducido (HR), sulfato ferroso (SF) o fumarato ferroso (FF), durante 24 semanas de almacenamiento. Material y métodos. Se evaluaron mediante una escala hedónica los atributos olor, sabor y color; a tiempo cero y cada ocho semanas, cada juez evaluó tres suplementos, mismo sabor, presentación y diferente SH. Participaron 70 mujeres. Resultados. Los SA sabor chocolate y plátano presentaron modificación del agrado por color y sabor durante el almacenamiento. Los SA con SF o HR presentaron el menor agrado para sabor y olor por efecto de las SH. En los SA sabor chocolate y natural adicionados con SF se afectó el color y el sabor. Conclusión. Los SA en general presentaron agrado; sin embargo, en las papillas adicionadas con SF y las bebidas con HR los atributos limitantes fueron color y sabor.

Para além do combate à ancilostomíase: o diário do médico norte-americano Alan Gregg / Looking beyond the campaign to eradicate ancylostomiasis: the diary of the American physician Alan Gregg

Entre 1916 e 1923, o Distrito Federal e 11 estados brasileiros estabeleceram acordos de cooperação com a divisão internacional de saúde – International Health Board – da Fundação Rockefeller para combater uma endemia rural, a ancilostomíase. Este breve texto apresenta o diário de Alan Gregg, um dos médicos norte-americanos que trabalharam no Brasil entre 1919-1922. Fonte interessante para discutir questões relativas à história da saúde pública no Brasil, o diário do médico, além das informações sobre as atividades de combate à ancilostomíase desenvolvidas pela Fundação Rockefeller no país, apresenta suas impressões relativas à natureza, à cultura, à política e à sociedade brasileiras. Na seleção de trechos do diário ora apresentado, priorizamos, porém, aspectos relativos às atividades profissionais realizadas por Gregg.

Between 1916 and 1923, the Federal District and 11 Brazilian states entered into cooperation agreements with the International Health Board of the Rockefeller Foundation to combat a rural endemic disease, namely ancylostomiasis. This paper presents the diary of Alan Gregg, one of the American physicians who worked in Brazil from 1919 to 1922. An interesting source to discuss issues relating to the history of public health in Brazil, in addition to information about the activities to combat ancylostomiasis developed by the Rockefeller Foundation in the country, the diary of the physician presents his impressions concerning nature, culture, politics and society in Brazil. In the diary excerpts presented here, however, aspects related to the professional activities performed by Gregg are prioritized.

Quantitative Assessment of Root Canal Roughness with Calcium-Based Hypochlorite Irrigants by 3D CLSM

Chemical solutions play important roles in endodontic treatment and promote ultrastructural changes in dentin surface. The aim of this study was to quantify root canal roughness at different concentrations of calcium hypochlorite (Ca(OCl)2) and sodium hypochlorite (NaOCl) by confocal laser scanning microscopy (CLSM). Fifty-two human mandibular premolars were sectioned and randomly organized into thirteen groups (n=8): saline (control); 1%, 2.5% and 5% NaOCl; 1%, 2.5% and 5% Ca(OCl)2; the hypochlorite groups were further divided into with or without EDTA. The chlorine concentrations of the different solutions were measured by iodine titration (%). The superficial roughness (Sa) was quantified by CLSM. Ca(OCl)2 presented substantial decrease in chlorine concentration that differed from the package indication, but without compromising the dentin ultrastructure changes. There were no significant differences in dentin roughness between Ca(OCl)2 or NaOCl at all studied concentrations. The combination with EDTA provided similar roughness values among the solutions (p>0.05). The 5% Ca(OCl)2 and NaOCl solutions significantly increased dentin roughness and did not differ from the EDTA association (p>0.05). Ca(OCl)2 promoted similar dentin roughness as the NaOCl at the same concentrations and combined with EDTA. It may be concluded that Ca(OCl)2 modified the root canal dentin roughness similarly to NaOCl, at the same concentrations and EDTA combinations used in this study. Ca(OCl)2 and NaOCl, both at 5%, significantly altered dentin roughness, overcoming EDTA association, thus Ca(OCl)2 concentrations ranging from 1% to 2.5% may be suitable solutions for root canal irrigation protocols.

Soluções químicas são fundamentais para o tratamento endodôntico; entretanto, promovem alterações ultraestruturais na superfície dentinária. O objetivo deste estudo foi quantificar a rugosidade da dentina radicular com diferentes concentrações de hipoclorito de cálcio (Ca(OCl)2) e hipoclorito de sódio (NaOCl) utilizando microscopia confocal à laser (CLSM). Foram utilizados 52 premolares humanos inferiores e aleatoriamente divididos em treze grupos (n=8): Soro fisiológico (controle); NaOCl a 1%, 2,5% and 5%; Ca(OCl)2 a 1%, 2,5% and 5%; os grupos de hipoclorito foram subdivididos pela associação ou não ao ácido etilenodiaminotetracético (EDTA). A concentração de cloro ativo foi avaliada para diferentes soluções utilizando titulação iodométrica (%). A rugosidade superficial (Sa) foi quantificada por CLSM. Ca(OCl)2 apresentou perda substancial de cloro ativo e que foi distinta da condição descrita pelo fabricante, sem entretanto comprometer as alterações no substrato dentinário. Não houve diferenças significantes na rugosidade dentinária produzida pelos Ca(OCl)2 e NaOCl em todas as concentrações estudadas e associação com EDTA. A associação ao EDTA produziu rugosidade semelhante entre as soluções (p>0.05). O Ca(OCl)2 e NaOCl na concentração de 5% aumentaram significativamente a rugosidade dentinária e não apresentaram diferenças dos valores obtidos com a associação de EDTA (p>0.05). O Ca(OCl)2 alterou a rugosidade da dentina radicular de forma semelhante ao NaOCl, nas concentrações e associações utilizadas neste estudo. Como a concentração de 5% de Ca(OCl)2 e NaOCl, apresentou maior rugosidade dentinária, independente da associação ao EDTA, pode-se concluir que Ca(OCl)2 nas concentrações de 1% e 2,5% pode ser considerado uma solução adequada para a irrigação de canais radiculares.

New frontiers in the study of memory mechanisms

We review recent work on three major lines of memory research: a) the possible role of the protein kinase M-zeta (PKMzeta) in memory persistence; b) the processes of “synaptic tagging and capture” in memory formation; c) the modulation of extinction learning, widely used in the psychotherapy of fear memories under the name of “exposure therapy”. PKMzeta is a form of protein kinase C (PKC) that apparently remains stimulated for months after the consolidation of a given memory. Synaptic tagging is a mechanism whereby the weak activation of one synapse can tag it with a protein so other synapses in the same cell can reactivate it by producing other proteins that bind to the tag. Extinction, once mistakenly labeled as a form of forgetting, is by itself a form of learning; through it animals can learn to inhibit a response. We now know it can be modulated by neurotransmitters or by synaptic tagging, which should enable better control of its clinical use.

Resistance exercise improves hippocampus-dependent memory

It has been demonstrated that resistance exercise improves cognitive functions in humans. Thus, an animal model that mimics this phenomenon can be an important tool for studying the underlying neurophysiological mechanisms. Here, we tested if an animal model for resistance exercise was able to improve the performance in a hippocampus-dependent memory task. In addition, we also evaluated the level of insulin-like growth factor 1/insulin growth factor receptor (IGF-1/IGF-1R), which plays pleiotropic roles in the nervous system. Adult male Wistar rats were divided into three groups (N = 10 for each group): control, SHAM, and resistance exercise (RES). The RES group was submitted to 8 weeks of progressive resistance exercise in a vertical ladder apparatus, while the SHAM group was left in the same apparatus without exercising. Analysis of a cross-sectional area of the flexor digitorum longus muscle indicated that this training period was sufficient to cause muscle fiber hypertrophy. In a step-through passive avoidance task (PA), the RES group presented a longer latency than the other groups on the test day. We also observed an increase of 43 and 94% for systemic and hippocampal IGF-1 concentration, respectively, in the RES group compared to the others. A positive correlation was established between PA performance and systemic IGF-1 (r = 0.46, P < 0.05). Taken together, our data indicate that resistance exercise improves the hippocampus-dependent memory task with a concomitant increase of IGF-1 level in the rat model. This model can be further explored to better understand the effects of resistance exercise on brain functions.

El cobre en la neurofisiología del hipocampo / Copper and hippocampus neurophysiology

Copper is an oligoelement essential for various enzymatic processes both in pathology and in human physiology. Its excessive accumulation in the liver and brain, particularly in the basal ganglia drives to the pathological syndrome known as Wilson's disease, on the other hand, this metal absence in the newborn provokes brain and cerebellar degeneration, pathology recognized as Menkes' disease. Currently its role in Parkinson, Alzheimer and lateral amyotrophic sclerosis is discussed. Our studies in rats about the copper effects in the hippocampus excitability, long term potentiation (LTP) and learning have shown a suppressor action on LTP, without memory alteration nor on the animal learning in the Morris' aquatic maze, a physiological paradoxical result and in its clinical inference also.

El cobre es un elemento esencial en diversos procesos fisiológicos y patológicos. Su acumulación excesiva en hígado, cerebro y particularmente en los ganglios basales, conduce al cuadro patológico conocido como la enfermedad de Wilson. Por otra parte, la ausencia de este metal en el recién nacido provoca degeneración cerebral y cerebelosa patología reconocida como enfermedad de Menkes. Actualmente se discute su papel en el Parkinson, Alzheimer y esclerosis lateral amiotrófica. Nuestros estudios en ratas han mostrado los efectos del cobre en la excitabilidad del hipocampo; su acción supresora de la LTP hipocámpica, sin alterar el aprendizaje y la memoria estudiados en el laberinto acuático de Morris, resultados paradójicos tanto desde la perspectiva neurofisiológica como en su inferencia clínica.

Longitudinal brain volumetric changes during one year in non-elderly healthy adults: a voxel-based morphometry study

Previous cross-sectional magnetic resonance imaging (MRI) studies of healthy aging in young adults have indicated the presence of significant inverse correlations between age and gray matter volumes, although not homogeneously across all brain regions. However, such cross-sectional studies have important limitations and there is a scarcity of detailed longitudinal MRI studies with repeated measures obtained in the same individuals in order to investigate regional gray matter changes during short periods of time in non-elderly healthy adults. In the present study, 52 healthy young adults aged 18 to 50 years (27 males and 25 females) were followed with repeated MRI acquisitions over approximately 15 months. Gray matter volumes were compared between the two times using voxel-based morphometry, with the prediction that volume changes would be detectable in the frontal lobe, temporal neocortex and hippocampus. Voxel-wise analyses showed significant (P < 0.05, family-wise error corrected) relative volume reductions of gray matter in two small foci located in the right orbitofrontal cortex and left hippocampus. Separate comparisons for males and females showed bilateral gray matter relative reductions in the orbitofrontal cortex over time only in males. We conclude that, in non-elderly healthy adults, subtle gray matter volume alterations are detectable after short periods of time. This underscores the dynamic nature of gray matter changes in the brain during adult life, with regional volume reductions being detectable in brain regions that are relevant to cognitive and emotional processes.

Correlations of recognition memory performance with expression and methylation of brain-derived neurotrophic factor in rats

Object recognition memory allows discrimination between novel and familiar objects. This kind of memory consists of two components: recollection, which depends on the hippocampus, and familiarity, which depends on the perirhinal cortex (Pcx). The importance of brain-derived neurotrophic factor (BDNF) for recognition memory has already been recognized. Recent evidence suggests that DNA methylation regulates the expression of BDNF and memory. Behavioral and molecular approaches were used to understand the potential contribution of DNA methylation to recognition memory. To that end, rats were tested for their ability to distinguish novel from familiar objects by using a spontaneous object recognition task. Furthermore, the level of DNA methylation was estimated after trials with a methyl-sensitive PCR. We found a signifcant correlation between performance on the novel object task and the expression of BDNF, negatively in hippocampal slices and positively in perirhinal cortical slices. By contrast, methylation of DNA in CpG island 1 in the promoter of exon 1 in BDNF only correlated in hippocampal slices, but not in the Pxc cortical slices from trained animals. These results suggest that DNA methylation may be involved in the regulation of the BDNF gene during recognition memory, at least in the hippocampus.

[Interaction between dopamine D2 and NMDA receptors in the dorsal hippocampus of rats in the elevated plus-maze test of anxiety]

Different studies have indicated that glutamate and dopamine are involved in producing anxiety. Furthermore, interaction between NMDA and dopamine receptors has been demonstrated in the modulation of some behaviors. In the present study, the role of dopaminergic D2 receptor in producing anxiety-like behavior induced by inhibition of NMDA receptors was investigated in male wistar rats. Rats were anesthetized with intra-peritoneal injection of ketamine hydrochloride, plus xylazine and then placed in a stereotaxic apparatus. Two stainless-steel cannuale were placed in the CA1 region of hippocampus. All animals were allowed to recover for one week before beginning behavioral test. The elevated plus maze test was used to test anxiety-like behaviors. The results of this study showed that intra-CA1 injection of MK801 [2 micro g/rat] induced anxiolytic effects. Intra-CA1 injection sulpiride [0.25, 0.5 and 0.75 micro g/rat] by itself had no effect on anxiety-like behaviors, but administration of the same doses of sulpiride 5 mins before injection of the effective dose of MK801 [2 micro g/rat, intra-CA1] inhibited anxiolytic effects of MK801. The results indicated that CA1 region of hippocampus have an important role in anxiolytic effects of MK801; and anxiolytic effect of NMDA receptors antagonist is at least partly mediated via D2 receptors of the dorsal hippocampus

Effect of acute changes in glucose concentration on neuronal activity and plasticity in the rat hippocampus / Efecto de los cambios agudos en la concentración de glucosa sobre la actividad neuronal y la plasticidad en el hipocampo de las ratas

OBJETIVES: Diabetes mellitus is a major public health concern in many regions of the world, including the Caribbean. Diabetes is associated with multi-system pathology and central nervous system complications have been receiving increasing attention (dementia, cognitive decline and memory loss). While such pathology has been shown to be associated with long term derangement in glucose metabolism,less is known about the effects of acute changes in glucose concentration on neuronal function. This study assesses the effects of acute changes in glucose concentration upon neuronal transmission and neuronal plasticity. METHODS: We made use of extracellular recordings from hippocampal slices of young adult rats and exposed them to changes in glucose concentration for 60 minutes before assessing synaptic plasticity. Experiments were carried out at both 30ºC and 35ºC. RESULTS: At 30ºC, glucose concentrations of 30 mM and 4 mM had little effect upon population spike potentials (PSP). However, reducing glucose concentration to 2 mM, 1 mM and 0 mM respectively resulted in a progressive decrease in the size of PSP until they were completely abolished. Similar results were observed at 35ºC except that 30 mM caused a significant increase in PSP size. Changes in glucose concentration had no effect upon synaptic plasticity at either 30ºC or 35ºC except below 2 mM glucose. CONCLUSION: Acute changes in glucose concentration have a limited impact on neuronal transmission unless concentrations drop below 2 mM. However, there seems to be little impairment of synaptic plasticity even at very low concentrations of glucose. We suggest that short term acute changes in glucose concentrations may not contribute directly to the cognitive decline associated with diabetes unless extremely severe.

OBJETIVOS: La diabetes mellitus es una de las principales preocupaciones de la salud pública en muchas regiones del mundo, incluyendo el Caribe. La diabetes se encuentra asociada con una patología multi-sistémica, y en tiempos recientes las complicaciones del sistema nervioso central han estado recibiendo cada vez mayor atención, incluyendo la demencia, el deterioro cognitivo y la pérdida de la memoria. Si bien se ha demostrado que esta patología se encuentra asociada con trastornos a largo plazo del metabolismo de la glucosa, poco se sabe de los efectos de los cambios agudos en la concentración de la glucosa en el funcionamiento neuronal. Este estudio evalúa los efectos de los cambios agudos en la concentración de glucosa, sobre la transmisión y la plasticidad neuronales. MÉTODOS:Se hizo uso de grabaciones extracelulares de segmentos del hipocampo de ratas adultas jóvenes. Las grabaciones fueron expuestas a cambios en la concentración de glucosa durante 60 minutos antes de evaluar la plasticidad sináptica. Los experimentos se llevaron a cabo a 30ºC y 35ºC. RESULTADOS: A 30ºC las concentraciones de glucosa de 30 mM y 4 mM tuvieron poco efecto sobre los potenciales de punta PSP (Population Spike Potentials). Sin embargo, la reducción de la concentración de glucosa a 2 mM, 1 mM y 0 mM respectivamente trajo como resultado una progresiva disminución del tamaño de los PSP hasta llegar a su total anulación. Resultados similares que observaron a 35ºC excepto en el caso de 30 mM, en el que se produjo un aumento significativo en la magnitud de los PSP. Los cambios en la concentración de glucosa no tuvieron efecto alguno sobre la plasticidad sináptica a 30ºC ni a 35ºC excepto por debajo de 2 mM de glucosa. CONCLUSIÓN: Los cambios agudos en la concentración de la glucosa tienen un impacto limitado sobre la transmisión neuronal a menos que las concentraciones caigan por debajo de 2 mM. Sin embargo, al parecer hay poca afectación de la plasticidad sináptica, incluso a concentraciones muy bajas de glucosa. Sugerimos que los cambios agudos a corto plazo de las concentraciones de glucosa pueden no contribuir directamente al deterioro cognitivo asociado con la diabetes, a menos que sea extremadamente severa.

Upregulation of the inducible nitric oxide synthase in rat hippocampus in a model of Alzheimer's disease: a possible mechanism of aluminium induced Alzheimer's

Alzheimer's disease attacks the brain causing gradual memory loss. Alzheimer's brain showed excess beta amyloid protein and neurofibrillary tangles, containing deposition of aluminium. Increasing evidence suggests that many neurons may die through apoptosis in Alzheimer's. Inducible nitric oxide synthase [iNOS] derived nitric oxide [NO] has been implicated in this process of neuronal cell death and apoptosis. Aluminium is considered a potential etiological factor in Alzheimer's disease and was used to produce an animal model of Alzheimer's. However, the exact mechanisms of aluminium induced Alzheimer's and neurotoxicity remain largely unknown. The present study was carried out to investigate the profile of the expression of iNOS in the hippocampus in an animal model of Alzheimer's produced by aluminium administration. Twenty four adult male albino rats were divided equally into four groups. Group I was the untreated control, groups II, III and IV were given aluminium chloride [300 mg/kg body weight] orally daily for one week, two and four weeks, respectively. At the end of the experiment, rats were killed by decapitation under brief anaesthesia. The brains were removed and processed for immunohistochemistry using antibody raised against iNOS. Results: By comparison to the untreated control, aluminium treated rats showed significant [P<0.05] increase in the expression of iNOS in the hippocampus. The expression was mainly neuronal and was seen in all areas. Additionally. administration of aluminium for four weeks caused marked histological changes with significant [P <0.05] reduction in hippocampus neuronal number and distortion of neuronal morphology. These data provide further evidence that exposure to aluminium may contribute to pathogenesis of Alzheimer 's and neurotoxicity by induction ofiNOS with subsequent increase in NO production that potentiate neuronal cell death in hippocampus

The evidence for hippocampal long-term potentiation as a basis of memory for simple tasks

Long-term potentiation (LTP) is the enhancement of postsynaptic responses for hours, days or weeks following the brief repetitive afferent stimulation of presynaptic afferents. It has been proposed many times over the last 30 years to be the basis of long-term memory. Several recent findings finally supported this hypothesis: a) memory formation of one-trial avoidance learning depends on a series of molecular steps in the CA1 region of the hippocampus almost identical to those of LTP in the same region; b)hippocampal LTP in this region accompanies memory formation of that task and of another similar task. However, CA1 LTP and the accompanying memory processes can be dissociated, and in addition plastic events in several other brain regions(amygdala, entorhinal cortex, parietal cortex) are also necessary for memory formation of the one-trial task, and perhaps of many others.

A potenciação de longa duração (LTP) é o aumento de respostas pós-sinápticas durante horas, dias ou semanas após a breve estimulação repetitiva de aferentes pre-sinápticos. Foi proposto durante 30 anos ser a base da memória de longa duração. Vários achados recentes finalmente apoiaram esta hipótese: a) a formação da memória de esquiva inibitória adquirida numa sessão depende de uma cadeia de processos moleculares na região CA1 do hipocampo quase idêntica à da LTP nessa mesma região; b) LTP hipocampal nessa região acompanha a formação da memóría dessa tarefa e de outra semelhante. No entanto, a LTP de CA1 e os processos de memória podem ser dissociados e, fora disso, processos plásticos em outras regiões cerebrais (amígdala, córtex entorrinal, córtex parietal) também são necessários para a formação da memória da tarefa de uma sessão e talvez de muitas outras.