A Continuous Attractor Model with Realistic Neural and Synaptic Properties Quantitatively Reproduces Grid Cell Physiology.

Computational simulations with data-driven physiological detail can foster a deeper understanding of the neural mechanisms involved in cognition. Here, we utilize the wealth of cellular properties from Hippocampome.org to study neural mechanisms of spatial coding with a spiking continuous attractor network model of medial entorhinal cortex circuit activity. The primary goal is to investigate if adding such realistic constraints could produce firing patterns similar to those measured in real neurons. Biological characteristics included in the work are excitability, connectivity, and synaptic signaling of neuron types defined primarily by their axonal and dendritic morphologies. We investigate the spiking dynamics in specific neuron types and the synaptic activities between groups of neurons. Modeling the rodent hippocampal formation keeps the simulations to a computationally reasonable scale while also anchoring the parameters and results to experimental measurements. Our model generates grid cell activity that well matches the spacing, size, and firing rates of grid fields recorded in live behaving animals from both published datasets and new experiments performed for this study. Our simulations also recreate different scales of those properties, e.g., small and large, as found along the dorsoventral axis of the medial entorhinal cortex. Computational exploration of neuronal and synaptic model parameters reveals that a broad range of neural properties produce grid fields in the simulation. These results demonstrate that the continuous attractor network model of grid cells is compatible with a spiking neural network implementation sourcing data-driven biophysical and anatomical parameters from Hippocampome.org. The software (version 1.0) is released as open source to enable broad community reuse and encourage novel applications.

A Continuous Attractor Model with Realistic Neural and Synaptic Properties Quantitatively Reproduces Grid Cell Physiology.

Computational simulations with data-driven physiological detail can foster a deeper understanding of the neural mechanisms involved in cognition. Here, we utilize the wealth of cellular properties from Hippocampome.org to study neural mechanisms of spatial coding with a spiking continuous attractor network model of medial entorhinal cortex circuit activity. The primary goal was to investigate if adding such realistic constraints could produce firing patterns similar to those measured in real neurons. Biological characteristics included in the work are excitability, connectivity, and synaptic signaling of neuron types defined primarily by their axonal and dendritic morphologies. We investigate the spiking dynamics in specific neuron types and the synaptic activities between groups of neurons. Modeling the rodent hippocampal formation keeps the simulations to a computationally reasonable scale while also anchoring the parameters and results to experimental measurements. Our model generates grid cell activity that well matches the spacing, size, and firing rates of grid fields recorded in live behaving animals from both published datasets and new experiments performed for this study. Our simulations also recreate different scales of those properties, e.g., small and large, as found along the dorsoventral axis of the medial entorhinal cortex. Computational exploration of neuronal and synaptic model parameters reveals that a broad range of neural properties produce grid fields in the simulation. These results demonstrate that the continuous attractor network model of grid cells is compatible with a spiking neural network implementation sourcing data-driven biophysical and anatomical parameters from Hippocampome.org. The software is released as open source to enable broad community reuse and encourage novel applications.

Mechanical complications of weekly care and maintenance versus once every 10 days of the peripherally inserted central catheter line insertion site in newborns: A propensity score-matched cohort study in Mexico.

PURPOSE: To evaluate the mechanical complications of weekly care and maintenance versus once every 10 days of the peripherally inserted central catheter (PICC) line insertion site versus once every 10 days in newborns. DESIGN AND METHODS: Prospective propensity score matched cohort study. Care and maintenance of the PICC line insertion site were performed on days 7 and 10 during January 2018 to December 2019. To compare mechanical complications, propensity score matching was performed. Propensity scores were used to determine the relative risks and hazard ratios by using logistic regressions with log-link function and Cox regressions, respectively. RESULTS: We included 175 newborns hospitalized in the neonatal intensive care unit (NICU) who underwent insertion of a PICC line. Ninety-six received weekly care and maintenance, and 79 received care and maintenance every 10 days. Weekly care and maintenance were associated with more breakage (RR 1.98, 95% CI 1.68-2.34); occlusions (RR 0.81, 95% CI 0.46-1.42) and accidental withdrawals (RR 1.31, 95% CI 0.93-1.84) were not different between care and maintenance every 7 and 10 days. A survival analysis was performed, showing that weekly care and maintenance are a risk factor for removal for mechanical complications (HR 7.61, 95% CI 3.05-19.01). CONCLUSION: We concluded that care and maintenance of the PICC in newborns every 10 days have fewer complications than when performing care and maintenance every 7 days. PRACTICE IMPLICATIONS: Newborns requiring intravenous therapy will benefit from care and maintenance every 10 days, and this practice could potentially spread to other NICUs.

Septal medial/diagonal band of Broca citalopram infusion reduces place learning efficiency and alters septohippocampal theta learning-related activity in rats.

Increases in power and frequency of hippocampal theta activity have been related to efficient place learning and memory acquisition in hippocampal-dependent tests. The complex medial septum-diagonal band of Broca (MS/DBB) is the pacemaker of hippocampal theta activity, influenced by the ascending synchronizing system, and modulated by serotonergic raphe medial afferents, acting on cholinergic and GABAergic septal neurons. The suppression of hippocampal theta expression and the modulation of hippocampal learning and memory are attributed to serotonin. To simultaneously test these hypotheses, a daily local serotonin increase was induced by citalopram (CIT) infusion (100 µM, 0.88 µl, 0.2 µl/m) 15 min before training in the Morris water maze. The theta activity was recorded in the MS/DBB, dentate gyrus (DG) and CA1 of one group infused with artificial cerebrospinal liquid (ACL) and the other with CIT on Days 1-6 of training. After a probe trial (Day 7) and one resting day, the treatments were reversed (Days 8-11). The CIT MS/DBB infusion in the first 6 training days reduced the efficiency of spatial learning in association with reduced power in the DG, reduced MS/DBB-DG coherence, increased DG-CA1 coherence, and a lack of a negative correlation between MS/DBB power and swam distances. No effect of the CIT occurred once the information was acquired under ACL training. These results support a role of serotonin, in acting on the MS/DBB in the fine tuning of hippocampal learning and memory efficiency through the modulation of learning-related theta activity power and septohipocampal synchronization.

Dynamics of Insulin Signaling in the Black-Legged Tick, Ixodes scapularis.

Insulin-like peptides (ILPs) have been identified in several invertebrates, particularly insects, and work on these ILPs has revealed many roles including regulation of energy homeostasis, growth, development, and lifespan to name a few. However, information on arthropod ILPs outside of insects is sparse. Studies of Ixodid tick ILPs are particularly scarce, despite their importance as vectors of infectious agents, most notably Lyme disease. The recent publication of the genome of the black-legged tick, Ixodes scapularis, has advanced opportunities to study this organism from a molecular standpoint, a resource sorely needed for an organism with challenging life history requirements for study in the laboratory, such as a long life cycle and obligate, prolonged, blood-feeding at each life stage. Through bioinformatics searches of the tick genome and other available I. scapularis databases, we identified four putative ILP sequences. Full-length sequences of these ILP transcripts were confirmed, and quantitative RT-PCR was used to examine expression levels of these ILPs in different life stages, feeding states, and adult tissues. This work serves as an initial characterization of ILP expression in ticks and provides the foundation for further exploration of the roles of ILPs in these important arthropod vectors.

Serotonergic modulation of septo-hippocampal and septo-mammillary theta activity during spatial learning, in the rat.

Theta activity has been related to the processing of spatial information and the formation of hippocampus-dependent memory. The medial septum (MS) plays an important role in the control and coordination of theta activity, as well as in the modulation of learning. It has been established that increased serotonergic activity may desynchronize theta activity, while reduced serotonergic activity produces continuous and persistent theta activity in the hippocampus. We investigate whether serotonin acting on the medial septum could modify spatial learning and the functional relationship between septo-hippocampal and septo-mammillary theta activity. The serotonin was depleted (5HT-D) from the medial septum by the injection of 5,7 DHT (5,7- dihydroxytryptamine). Theta activity was recorded in the dorsal hippocampus, MS and mammillary nuclei (SUM, MM) of Sprague-Dawley male rats during spatial learning in the Morris water maze. Spatial learning was facilitated, and the frequency of the hippocampal theta activity during the first days of training increased (to 8.5Hz) in the 5HT-D group, unlike the vehicle group. Additionally, the coherence between the MS-hippocampus and the MS-mammillary nuclei was higher during the second day of the test compared to the vehicle group. We demonstrated that septal serotonin depletion facilitates the acquisition of spatial information in association with a higher functional coupling of the medial septum with the hippocampus and mammillary nuclei. Serotonin, acting in the medial septum, modulates hippocampal theta activity and spatial learning.

Hippocampal strata theta oscillations change their frequency and coupling during spatial learning.

The theta rhythm is necessary for hippocampal-dependent spatial learning. It has been proposed that each hippocampal stratum can generate a current theta dipole. Therefore, considering that each hippocampal circuit (CA1, CA3, and Dentate Gyrus (DG)) contributes differently to distinct aspects of a spatial memory, the theta oscillations on each stratum and their couplings may exhibit oscillatory dynamics associated with different stages of learning. To test this hypothesis, the theta oscillations from five hippocampal strata were recorded in the rat during different stages of learning in a Morris maze. The peak power, the relative power (RP) and the coherence between hippocampal strata were analyzed. The early acquisition stage of the Morris task was characterized by the predominance of slow frequency theta activity and high coupling between specific hippocampal strata at slow frequencies. However, on the last training day, the theta oscillations were faster in all hippocampal strata, with tighter coupling at fast frequencies between the CA3 pyramidal stratum and other strata. Our results suggest that modifications to the theta frequency and its coupling can be a means by which the hippocampus differentially operates during acquisition and retrieval states.

Presence of enteric viruses in water samples for consumption in Colombia: Challenges for supply systems.

INTRODUCTION: Since drinking water can be a vehicle for the transmission of pathogens, the detection of enteric viruses in these water samples is essential to establish the appropriate measures to control and prevent associated diseases.  OBJECTIVE: To analyze the results obtained for enteric viruses in water samples for human consumption received at the Colombian Instituto Nacional de Salud and establish their association with the data on water quality in Colombian municipalities.  MATERIALS AND METHODS: We conducted a descriptive-retrospective analysis of the results obtained in the detection of rotavirus, enterovirus, hepatitis A virus and adenovirus in water samples received for complementary studies of enteric hepatitis, acute diarrheal disease and foodborne diseases. Data were correlated with the results of water quality surveillance determined by the national human consumption water quality index (IRCA).  RESULTS: Of the 288 samples processed from 102 Colombian municipalities, 50.7% were positive for viruses: 26.73% for hepatitis A virus, 20.48% for enterovirus and rotavirus and 18.05% for adenovirus. Viruses were detected in 48.26% of non-treated water samples and in 45.83% of treated water samples. The IRCA index showed no correlation with the presence of viruses.  CONCLUSIONS: The presence of viruses in water represents a public health risk and, therefore, the prevention of virus transmission through water requires appropriate policies to reinforce water supply systems and improve epidemiological surveillance.

Presencia de virus entéricos en muestras de agua para el consumo humano en Colombia: desafíos de los sistemas de abastecimiento / Presence of enteric viruses in water samples for consumption in Colombia: Challenges for supply systems

Introducción. El agua de consumo humano puede ser vehículo de transmisión de agentes patógenos. La detección de virus entéricos en estas muestras de agua es esencial para establecer las acciones adecuadas de control y prevención de las enfermedades asociadas. Objetivo. Analizar los resultados del diagnóstico de virus entéricos en muestras de agua para el consumo humano recibidas en el Instituto Nacional de Salud y establecer su asociación con los datos sobre la calidad del agua en los municipios de Colombia. Materiales y métodos. Se hizo un análisis descriptivo retrospectivo de los resultados obtenidos en la detección de rotavirus, enterovirus, virus de la hepatitis A y adenovirus, en muestras de agua recibidas para estudios complementarios en la investigación de brotes de hepatitis entérica, de enfermedad diarreica aguda y de enfermedades transmitidas por alimentos. Dicha información se correlacionó con los datos de la vigilancia de la calidad del agua municipal determinada según el índice de riesgo de la calidad del agua (IRCA). Resultados. Se procesaron 288 muestras de 102 municipios de Colombia, de las cuales el 50,7 % fue positivo para algún virus: 26,73 %, para el virus de la hepatitis A; 20,48 %, para enterovirus y rotavirus, y 18,05 % para adenovirus. Se detectaron virus en 48,26 % de las muestras de agua no tratada y en 45,83 % de las de agua tratada. El IRCA no mostró correlación con la presencia de virus. Conclusiones. La presencia de virus en el agua representa un riesgo para la salud pública. La prevención de la transmisión de virus por medio del agua requiere políticas para fortalecer los sistemas de suministro y para mejorar la vigilancia epidemiológica.

Introduction: Since drinking water can be a vehicle for the transmission of pathogens, the detection of enteric viruses in these water samples is essential to establish the appropriate measures to control and prevent associated diseases. Objective: To analyze the results obtained for enteric viruses in water samples for human consumption received at the Colombian Instituto Nacional de Salud and establish their association with the data on water quality in Colombian municipalities. Materials and methods: We conducted a descriptive-retrospective analysis of the results obtained in the detection of rotavirus, enterovirus, hepatitis A virus and adenovirus in water samples received for complementary studies of enteric hepatitis, acute diarrheal disease and foodborne diseases. Data were correlated with the results of water quality surveillance determined by the national human consumption water quality index (IRCA). Results: Of the 288 samples processed from 102 Colombian municipalities, 50.7% were positive for viruses: 26.73% for hepatitis A virus, 20.48% for enterovirus and rotavirus and 18.05% for adenovirus. Viruses were detected in 48.26% of non-treated water samples and in 45.83% of treated water samples. The IRCA index showed no correlation with the presence of viruses. Conclusions: The presence of viruses in water represents a public health risk and, therefore, the prevention of virus transmission through water requires appropriate policies to reinforce water supply systems and improve epidemiological surveillance.

Supramammillary serotonin reduction alters place learning and concomitant hippocampal, septal, and supramammillar theta activity in a Morris water maze.

Hippocampal theta activity is related to spatial information processing, and high-frequency theta activity, in particular, has been linked to efficient spatial memory performance. Theta activity is regulated by the synchronizing ascending system (SAS), which includes mesencephalic and diencephalic relays. The supramamillary nucleus (SUMn) is located between the reticularis pontis oralis and the medial septum (MS), in close relation with the posterior hypothalamic nucleus (PHn), all of which are part of this ascending system. It has been proposed that the SUMn plays a role in the modulation of hippocampal theta-frequency; this could occur through direct connections between the SUMn and the hippocampus or through the influence of the SUMn on the MS. Serotonergic raphe neurons prominently innervate the hippocampus and several components of the SAS, including the SUMn. Serotonin desynchronizes hippocampal theta activity, and it has been proposed that serotonin may regulate learning through the modulation of hippocampal synchrony. In agreement with this hypothesis, serotonin depletion in the SUMn/PHn results in deficient spatial learning and alterations in CA1 theta activity-related learning in a Morris water maze. Because it has been reported that SUMn inactivation with lidocaine impairs the consolidation of reference memory, we asked whether changes in hippocampal theta activity related to learning would occur through serotonin depletion in the SUMn, together with deficiencies in memory. We infused 5,7-DHT bilaterally into the SUMn in rats and evaluated place learning in the standard Morris water maze task. Hippocampal (CA1 and dentate gyrus), septal and SUMn EEG were recorded during training of the test. The EEG power in each region and the coherence between the different regions were evaluated. Serotonin depletion in the SUMn induced deficient spatial learning and altered the expression of hippocampal high-frequency theta activity. These results provide evidence in support of a role for serotonin as a modulator of hippocampal learning, acting through changes in the synchronicity evoked in several relays of the SAS.

[Quality of water for human consumption and its association with morbimortality in Colombia, 2008-2012]. / La calidad del agua para consumo humano y su asociación con la morbimortalidad en Colombia, 2008-2012.

INTRODUCTION: The quality of water for human consumption has been correlated with the occurrence of different diseases. Studying the relationship between these parameters would allow determining the impact of water quality on human health, and to direct preventative measures and promote environmental health. OBJECTIVE: To analyze the quality of water intended for human consumption and its association with morbimortality in Colombia, 2008-2012. MATERIALS AND METHODS: The database for surveillance of water quality was analyzed by means of descriptive statistics of the principal indicators (total coliforms, Escherichia coli , turbidity, color, pH, free residual chlorine and water quality risk index). The results were correlated with infant mortality and morbidity due to acute diarrheal diseases, foodborne diseases and hepatitis A. A risk map was prepared to identify those municipalities with the highest risk of water contamination and infant mortality. RESULTS: A high percentage of municipalities did not conform to existing standards for water potability values. Problems were identified that were related to presence of E. coli and total coliforms, as well as absence of free residual chlorine, a situation that was exacerbated in rural areas. Water quality showed a high correlation with infant mortality, highlighting its importance for children's health. CONCLUSION: Water quality was found to have an important impact on infant mortality. Improving water quality in Colombia will require policies that strengthen water supply systems in this country. Strengthening of environmental health surveillance programs is essential to guide actions aimed at improving water quality and exert a positive impact on health.

La calidad del agua para consumo humano y su asociación con la morbimortalidad en Colombia, 2008-2012 / Quality of water for human consumption and its association with morbimortality in Colombia, 2008-2012

Introducción. La calidad del agua para consumo humano se ha asociado con la aparición de diversas enfermedades. El estudio de la relación entre estos eventos permitiría reflejar el impacto de la calidad del agua de consumo en la salud de la población, con el fin de orientar acciones de prevención y promoción en salud ambiental. Objetivo. Analizar la calidad del agua para consumo humano y su asociación con la morbimortalidad en Colombia, 2008-2012. Materiales y métodos. Se analizó la base de datos de la vigilancia de la calidad del agua mediante métodos de estadística descriptiva en lo referente a las principales características indicadoras de calidad (coliformes totales, Escherichia coli , turbiedad, color, pH, cloro residual libre e índice del riesgo de la calidad del agua). Los resultados se correlacionaron con la mortalidad infantil y la morbilidad por enfermedad diarreica aguda, enfermedades transmitidas por alimentos y hepatitis A. Se elaboró un mapa de riesgo para identificar los municipios con alto riesgo de contaminación del agua y mortalidad infantil. Resultados. Se encontró un alto porcentaje de municipios en los que el valor de potabilidad del agua no se ajustaba a lo establecido por la norma vigente; se identificaron los problemas relacionados con la presencia de E. coli , de coliformes totales y la ausencia de cloro residual libre, los cuales fueron más agudos en la zona rural. La calidad del agua tuvo una mayor correlación con la mortalidad infantil, constatándose así su importancia para la salud de la población infantil. Conclusión. La calidad del agua demostró tener un impacto importante en la mortalidad infantil, por lo que se requiere la adopción de políticas que fortalezcan los sistemas de suministro de agua en el país. Es esencial fortalecer los programas de vigilancia en salud ambiental, para orientar las acciones de mejoramiento de la calidad del agua e influir positivamente en la salud.

Introduction: The quality of water for human consumption has been correlated with the occurrence of different diseases. Studying the relationship between these parameters would allow determining the impact of water quality on human health, and to direct preventative measures and promote environmental health. Objective: To analyze the quality of water intended for human consumption and its association with morbimortality in Colombia, 2008-2012. Materials and methods: The database for surveillance of water quality was analyzed by means of descriptive statistics of the principal indicators (total coliforms, Escherichia coli , turbidity, color, pH, free residual chlorine and water quality risk index). The results were correlated with infant mortality and morbidity due to acute diarrheal diseases, foodborne diseases and hepatitis A. A risk map was prepared to identify those municipalities with the highest risk of water contamination and infant mortality. Results: A high percentage of municipalities did not conform to existing standards for water potability values. Problems were identified that were related to presence of E. coli and total coliforms, as well as absence of free residual chlorine, a situation that was exacerbated in rural areas. Water quality showed a high correlation with infant mortality, highlighting its importance for children´s health. Conclusion: Water quality was found to have an important impact on infant mortality. Improving water quality in Colombia will require policies that strengthen water supply systems in this country. Strengthening of environmental health surveillance programs is essential to guide actions aimed at improving water quality and exert a positive impact on health.

[Surveillance of drinking-water quality: assessing the degree of implementation of actions]. / Vigilância da Qualidade da Água para Consumo Humano: avaliando o grau de implementação das ações.

This study aims to evaluate the Drinking-Water Quality Surveillance Programme (DWQS) implemented in Colombia. The study was conducted using methodology for assessing the implementation, integrating a normative assessment and evaluation research. For this assessment, Delphi methodology was developed that allowed the definition of an evaluation matrix, composed of 14 attributes and 62 criteria, as well as the building of a score system and parameters that permitted the evaluation of each of the defined criteria. Data collection involved conducting semi-structured interviews with institutional actors from 39 territorial units. The system evaluation showed that the DWQS in Colombia is partially implemented, with different stages of implementation in territorial units. The system showed a strengthening in actions related to data production on the aspect for improving water quality and DWQS actions from the standpoint of health promotion. However, some conceptual limitations were identified in terms of legislation thereby affecting the fulfilment of the universality of DWQS actions.

Vigilância da Qualidade da Água para Consumo Humano: avaliando o grau de implementação das ações / Surveillance of drinking-water quality: assessing the degree of implementation of actions

O presente estudo teve como objetivo avaliar a implementação do Sistema de Vigilância da Qualidade da Água para Consumo Humano (VQACH), na Colômbia. O estudo foi realizado mediante a metodologia de avaliação da implementação, integrando avaliação normativa e pesquisa de avaliação. Para a avaliação foi desenvolvida metodologia Delphi, permitindo definir uma matriz avaliativa, composta por 14 atributos e 62 critérios, e a construção de um sistema de escores e parâmetros, que possibilitou a avaliação de cada um dos critérios definidos. A coleta de dados envolveu a realização de entrevistas semiestruturadas com atores institucionais de 39 unidades territoriais. A avaliação mostrou que o sistema de VQACH está parcialmente implementado, com diferentes estados de implementação nas unidades territoriais. O sistema mostra um fortalecimento nas ações relacionadas com produção de dados sobre as condições da qualidade da água, com ausência de ações que permitam o aproveitamento desses dados para o melhoramento da qualidade de água, e de ações de VQACH na perspectiva de promoção da saúde. Foram identificadas algumas limitações conceituais nas legislações, o que afeta o cumprimento da universalidade das ações de VQACH.

This study aims to evaluate the Drinking-Water Quality Surveillance Programme (DWQS) implemented in Colombia. The study was conducted using methodology for assessing the implementation, integrating a normative assessment and evaluation research. For this assessment, Delphi methodology was developed that allowed the definition of an evaluation matrix, composed of 14 attributes and 62 criteria, as well as the building of a score system and parameters that permitted the evaluation of each of the defined criteria. Data collection involved conducting semi-structured interviews with institutional actors from 39 territorial units. The system evaluation showed that the DWQS in Colombia is partially implemented, with different stages of implementation in territorial units. The system showed a strengthening in actions related to data production on the aspect for improving water quality and DWQS actions from the standpoint of health promotion. However, some conceptual limitations were identified in terms of legislation thereby affecting the fulfilment of the universality of DWQS actions.

Septal serotonin depletion in rats facilitates working memory in the radial arm maze and increases hippocampal high-frequency theta activity.

Hippocampal theta activity, which is strongly modulated by the septal medial/Broca׳s diagonal band neurons, has been linked to information processing of the hippocampus. Serotonin from the medial raphe nuclei desynchronises hippocampal theta activity, whereas inactivation or a lesion of this nucleus induces continuous and persistent theta activity in the hippocampus. Hippocampal serotonin depletion produces an increased expression of high-frequency theta activity concurrent with the facilitation of place learning in the Morris maze. The medial septum-diagonal band of Broca complex (MS/DBB) has been proposed as a key structure in the serotonin modulation of theta activity. We addressed whether serotonin depletion of the MS/DBB induces changes in the characteristics of hippocampal theta activity and whether the depletion is associated with learning in a working memory spatial task in the radial arm maze. Sprague Dawley rats were depleted of 5HT with the infusion of 5,7-dihydroxytriptamine (5,7-DHT) in MS/DBB and were subsequently trained in the standard test (win-shift) in the radial arm, while the CA1 EEG activity was simultaneously recorded through telemetry. The MS/DBB serotonin depletion induced a low level of expression of low-frequency (4.5-6.5Hz) and a higher expression of high-frequency (6.5-9.5Hz) theta activity concomitant to a minor number of errors committed by rats on the working memory test. Thus, the depletion of serotonin in the MS/DBB caused a facilitator effect on working memory and a predominance of high-frequency theta activity.

Serotonergic modulation of hippocampal theta activity in relation to hippocampal information processing.

Hippocampal theta activity is the result of the concerted activity of a group of nuclei located in the brain stem and the caudal diencephalic area, which are together referred to as the synchronizing ascending system. Serotonin is recognized as the only neurotransmitter able to desynchronize the hippocampal electroencephalographic. A theory has been developed in which serotonin, acting on medial septal neurons, modulates cholinergic/GABAergic inputs to the hippocampus and, thus, the cognitive processing mediated by this area. However, few studies have addressed the relationship between serotonin modulation of theta activity and cognition. In this review, we present a summary and analysis of the data relating serotonin and its theta activity modulation with cognition, and we also discuss the few works relating serotonin, theta activity and cognition as well as the theories regarding the serotonin regulation of memory processes organized by the hippocampus. We propose that serotonin depletion induces impairment of the relays coding the frequency of hippocampal theta activity, whereas depletion of the relays in which frequency is not coded induces improvements in spatial learning that are related to increased expression of high-frequency theta activity.

Prefrontal electroencephalographic activity during the working memory processes involved in a sexually motivated task in male rats.

The prefrontal cortex is involved in working memory functions, and several studies using food or drink as rewards have demonstrated that the rat is capable of performing tasks that involve working memory. Sexual activity is another highly-rewarding, motivated behaviour that has proven to be an efficient incentive in classical operant tasks. The objective of this study was to determine whether the functional activity of the medial prefrontal cortex (mPFC) changes in relation to the working memory processes involved in a sexually motivated task performed in male rats. Thus, male Wistar rats implanted in the mPFC were subjected to a nonmatching-to-sample task in a T-maze using sexual interaction as a reinforcer during a 4-day training period. On the basis of their performance during training, the rats were classified as 'good-learners' or 'bad-learners'. Only the good-learner rats showed an increase in the absolute power of the 8-13 Hz band during both the sample and test runs; a finding that could be related to learning of the working memory elements entailed in the task. During the maintenance phase only (i.e., once the rule had been learned well), the good-learner rats also showed an increased correlation of the 8-13 Hz band during the sample run, indicating that a high degree of coupling between the prefrontal cortices is necessary for the processing required to allow the rats to make correct decisions in the maintenance phase. Taken together, these data show that mPFC activity changes in relation to the working memory processes involved in a sexually motivated task in male rats.

Serotonin depletion of supramammillary/posterior hypothalamus nuclei produces place learning deficiencies and alters the concomitant hippocampal theta activity in rats.

Hippocampal theta activity is important for the acquisition of spatial information and is strongly influenced and regulated by extra-hippocampal inputs from the synchronising ascending system (SAS), which includes the supramammillary nucleus (SUMn) and the posterior hypothalamic nucleus (PHn). Together these nuclei play an important role in controlling the frequency encoding of theta activity and are innervated by serotonin synapses, which also regulate theta activity and learning abilities. The participation of the SUMn in place learning and modulation of hippocampal theta activity were recently shown; thus, we questioned whether serotonin acting on SUMn/PHn could modulate place learning ability and concurrent hippocampal theta activity. The serotonergic terminals of the SUMn/PHn in rats were lesioned through 5,7-dihydroxytryptamine (5,7-DHT) infusion, and hippocampal theta activity during the Morris water maze test was recorded. Rats in the vehicle group learned the task efficiently and showed learning-related theta changes in the CA1 and dentate gyrus regions throughout the training. The 5-HT-depleted rats were deficient in the Morris water maze task and showed theta activity in the CA1 and dentate gyrus that were unrelated to the processing of learning. We conclude that serotonin can regulate the hippocampal theta activity acting on the SUMn/PHn relay of the SAS and that the influence of 5-HT in these nuclei is required for the learning-related changes in hippocampal theta activity that underlie the successful resolution of the Morris water maze task.

Differential learning-related changes in theta activity during place learning in young and old rats.

The participation key role of the hippocampus in place learning ability as well as the decline of cognitive functions associated with aging, have been established in experimental and clinical studies. On the other hand, hippocampal theta activity has been proposed as a part of the cerebral phenomena underlying hippocampal-dependent learning processes. In the present study, the relative power of low, high, and maximal frequency components of hippocampal CA1 theta activity during a 6-day training period (four daily trials; basal, searching, and platform stages) and the probe trial of a place learning paradigm (Morris water maze) were analyzed in young and aged rats. An increase in high frequency, and a decrease in low frequency relative power of theta activity during the searching stage, which were correlated with shorter swimming path lengths and predominant hippocampal-dependent allocentric strategies, were observed in young rats as became trained in place learning and memory tasks, in the Morris water maze; while, under these conditions, no changes in theta activity and predominant non hippocampal-dependent egocentric strategies occurred in the old rats. Besides, an overall (theta activity recorded during the three behavioral stages) increase of low frequency and an overall decrease of high frequency theta bands in the old group as compared to the young group were observed. These electrophysiological data suggest that old rats process information relevant for cognitive functions in a different manner, possibly leading to the use of different learning strategies, than young rats.

Hippocampal serotonin depletion facilitates place learning concurrent with an increase in CA1 high frequency theta activity expression in the rat.

Acetylcholine- and serotonin-dependent theta activities have been long proposed to exist. However, several studies have shown that serotonin tends to desynchronise hippocampal EEG activity. Theta activity has been related to the processing of hippocampal place learning. Since the serotonergic system can influence hippocampal theta activity, it could function as a modulator of spatial learning. For these reasons, we investigated the possible role of hippocampal serotonin in the regulation of theta activity during the acquisition of map-based spatial information. Following 5-HT hippocampal depletion through 5,7-dihydroxytriptamine-induced lesions to the fimbria, fornix and cingulate bundle of adult rats, CA1 hippocampal theta activity was recorded during place learning training. Only rats with reduction higher than 90% from controls, verified post-mortem by HPLC were studied. A facilitation of place learning after hippocampal serotonin depletion occurred, and was associated with earlier expression of dominant high frequency theta activity (6.5-9.5Hz). Therefore, theta activity was related to the accuracy of behavioural performance through 5-HT modulation in a place learning test.