Voces en un campo de sangre : Max Aub y los penúltimos episodios nacionales

Una cierta lectura de la posmodernidad ha diagnosticado (en realidad, ofertado) el final de la historia y, por consiguiente, el de la novela histórica, aunque algunos optamos por no enterrarla sino por renovarla. En el contexto de este debate vale la pena detenerse en el Laberinto mágico de Max Aub, magno mural de la guerra civil española, una de las últimas manifestaciones del modelo puro de episodio nacional, máximo legado de Galdós y Valle Inclán. A pesar de los elementos aparentemente heterogéneos que contiene, el gesto histórico e ideológico que traza Campo cerrado (escrita en 1939), la primera novela del Laberinto mágico, es el de la novela histórica moderna. En los Campos posteriores, la fórmula de la novela histórica aubiana alcanzará su sazón, siendo quizá Campo del moro (1963) el más brillante y equilibrado ejemplo de esta modalidad entre las de la serie. En ella, el sentido de la historia que se anunciaba en Campo del moro se disipa, víctima de la traición y asaltado por la locura que se desata en las calles de Madrid. Campo del moro puede considerarse novela histórica pura, ya que se cumplen en ella las condiciones de felicidad necesarias para que esta modalidad genérica se realice plenamente: historicidad de los acontecimientos; respeto al orden cronológico en que se suceden; ficcionalidad limitada por el referente histórico; iniciativa de lo histórico sobre lo ficcional y primacía de la lógica de lo público sobre la de lo privado; por último, narratibilidad de los acontecimientos que se manifiesta en la selección del golpe de estado de Casado y Besteiro y su potenciación como clave del relato histórico. Tres grandes temas se despliegan en la lógica argumental de la novela: la traición, la confusión del laberinto y la degradación de una causa heroica. En el discurso de Max Aub que alimenta la novela, la ficción, la verdad y la historia se entrelazan hasta formar el hilo de Ariadna en el Laberinto.

Voces en un campo de sangre : Max Aub y los penúltimos episodios nacionales

Una cierta lectura de la posmodernidad ha diagnosticado (en realidad, ofertado) el final de la historia y, por consiguiente, el de la novela histórica, aunque algunos optamos por no enterrarla sino por renovarla. En el contexto de este debate vale la pena detenerse en el Laberinto mágico de Max Aub, magno mural de la guerra civil española, una de las últimas manifestaciones del modelo puro de episodio nacional, máximo legado de Galdós y Valle Inclán. A pesar de los elementos aparentemente heterogéneos que contiene, el gesto histórico e ideológico que traza Campo cerrado (escrita en 1939), la primera novela del Laberinto mágico, es el de la novela histórica moderna. En los Campos posteriores, la fórmula de la novela histórica aubiana alcanzará su sazón, siendo quizá Campo del moro (1963) el más brillante y equilibrado ejemplo de esta modalidad entre las de la serie. En ella, el sentido de la historia que se anunciaba en Campo del moro se disipa, víctima de la traición y asaltado por la locura que se desata en las calles de Madrid. Campo del moro puede considerarse novela histórica pura, ya que se cumplen en ella las condiciones de felicidad necesarias para que esta modalidad genérica se realice plenamente: historicidad de los acontecimientos; respeto al orden cronológico en que se suceden; ficcionalidad limitada por el referente histórico; iniciativa de lo histórico sobre lo ficcional y primacía de la lógica de lo público sobre la de lo privado; por último, narratibilidad de los acontecimientos que se manifiesta en la selección del golpe de estado de Casado y Besteiro y su potenciación como clave del relato histórico. Tres grandes temas se despliegan en la lógica argumental de la novela: la traición, la confusión del laberinto y la degradación de una causa heroica. En el discurso de Max Aub que alimenta la novela, la ficción, la verdad y la historia se entrelazan hasta formar el hilo de Ariadna en el Laberinto.

Classification of coral reef types in Torres Strait (GIS files in zip-archive 319 kB)

Coral reefs represent major accumulations of calcium carbonate (CaCO3). The particularly labyrinthine network of reefs in Torres Strait, north of the Great Barrier Reef (GBR), has been examined in order to estimate their gross CaCO3 productivity. The approach involved a two-step procedure, first characterising and classifying the morphology of reefs based on a classification scheme widely employed on the GBR and then estimating gross CaCO3 productivity rates across the region using a regional census-based approach. This was undertaken by independently verifying published rates of coral reef community gross production for use in Torres Strait, based on site-specific ecological and morphological data. A total of 606 reef platforms were mapped and classified using classification trees. Despite the complexity of the maze of reefs in Torres Strait, there are broad morphological similarities with reefs in the GBR. The spatial distribution and dimensions of reef types across both regions are underpinned by similar geological processes, sea-level history in the Holocene and exposure to the same wind/wave energetic regime, resulting in comparable geomorphic zonation. However, the presence of strong tidal currents flowing through Torres Strait and the relatively shallow and narrow dimensions of the shelf exert a control on local morphology and spatial distribution of the reef platforms. A total amount of 8.7 million tonnes of CaCO3 per year, at an average rate of 3.7 kg CaCO3 m-2 yr-1 (G), were estimated for the studied area. Extrapolated production rates based on detailed and regional census-based approaches for geomorphic zones across Torres Strait were comparable to those reported elsewhere, particularly values for the GBR based on alkalinity-reduction methods. However, differences in mapping methodologies and the impact of reduced calcification due to global trends in coral reef ecological decline and changing oceanic physical conditions warrant further research. The novel method proposed in this study to characterise the geomorphology of reef types based on classification trees provides an objective and repeatable data-driven approach that combined with regional census-based approaches has the potential to be adapted and transferred to different coral reef regions, depicting a more accurate picture of interactions between reef ecology and geomorphology.

Voces en un campo de sangre : Max Aub y los penúltimos episodios nacionales

Una cierta lectura de la posmodernidad ha diagnosticado (en realidad, ofertado) el final de la historia y, por consiguiente, el de la novela histórica, aunque algunos optamos por no enterrarla sino por renovarla. En el contexto de este debate vale la pena detenerse en el Laberinto mágico de Max Aub, magno mural de la guerra civil española, una de las últimas manifestaciones del modelo puro de episodio nacional, máximo legado de Galdós y Valle Inclán. A pesar de los elementos aparentemente heterogéneos que contiene, el gesto histórico e ideológico que traza Campo cerrado (escrita en 1939), la primera novela del Laberinto mágico, es el de la novela histórica moderna. En los Campos posteriores, la fórmula de la novela histórica aubiana alcanzará su sazón, siendo quizá Campo del moro (1963) el más brillante y equilibrado ejemplo de esta modalidad entre las de la serie. En ella, el sentido de la historia que se anunciaba en Campo del moro se disipa, víctima de la traición y asaltado por la locura que se desata en las calles de Madrid. Campo del moro puede considerarse novela histórica pura, ya que se cumplen en ella las condiciones de felicidad necesarias para que esta modalidad genérica se realice plenamente: historicidad de los acontecimientos; respeto al orden cronológico en que se suceden; ficcionalidad limitada por el referente histórico; iniciativa de lo histórico sobre lo ficcional y primacía de la lógica de lo público sobre la de lo privado; por último, narratibilidad de los acontecimientos que se manifiesta en la selección del golpe de estado de Casado y Besteiro y su potenciación como clave del relato histórico. Tres grandes temas se despliegan en la lógica argumental de la novela: la traición, la confusión del laberinto y la degradación de una causa heroica. En el discurso de Max Aub que alimenta la novela, la ficción, la verdad y la historia se entrelazan hasta formar el hilo de Ariadna en el Laberinto.

El parque: Espacios, límites y jerarquías en la obra de SANAA

En los últimos tiempos, el estudio japonés SANAA ha realizado una serie de obras que le han puesto en el punto de mira de la arquitectura internacional, y que se ha visto reflejado en la concesión en el año 2010 del premio Pritzker a Kazuyo Sejima y Ryue Nishizawa por toda una carrera de trabajo ininterrumpido. SANAA ha construido una serie de edificios que han supuesto una gran influencia en el contexto de la arquitectura mundial y que está contribuyendo al trabajo de muchísimos arquitectos jóvenes, tanto en Japón como fuera de él, y su trabajo se estudia y analiza en las escuelas de arquitectura de medio mundo. La tesis doctoral, estudia el parque de SANAA desde las diversas formas en las que éste se presenta, parques por continuidad, o parques por acumulación, como una excusa para el estudio de los diferentes mecanismos arquitectónicos en los que se basa su modo de proyectar. Dichos mecanismos forman parte ya de una forma de proyectar contemporánea y su estudio permite la comprensión de algunos de los fenómenos arquitectónicos más interesantes que se están produciendo en la arquitectura de nuestro tiempo. La revelación de estos mecanismos supone el sacar a la luz gran parte de los procesos y desarrollos de proyecto, que por la lacónica manera de dibujar de SANAA, quedan ocultos la mayoría de las veces y, tan solo es percibido en una visita lenta y pausada por el edificio. El documento aquí presentado se convierte entonces, en una investigación, en la que el doctorando, como un detective, rastrea los proyectos de SANAA buscando aquellos mecanismos que permiten discernir el verdadero significado de conceptos como laberinto, jerarquía, orden, atmósfera o experiencia a lo largo de los principales proyectos de espacio horizontal de Sejima y Nishizawa. La tesis intenta por tanto dar forma a las principales referencias que constituyen el universo imaginario del estudio japonés y que, ya son parte de la cultura arquitectónica contemporánea. ABSTRACT In recent times, the Japanese Studio SANAA has produced a number of works that have taken it to the front sight of international architecture. This has led Kazuyo Sejima and Ryue Nishizawa to receiving the 2010 Pritzer award for an uninterrupted career. SANAA has built a series of buildings that have greatly influenced global architecture. Moreover, it is contributing to the work of many young architects, both in Japan and outside Japan. Its work is studied and assessed by architecture schools all over the world. This Doctoral thesis analyses the SANAA Park from all the perspectives it shows, parks by continuity or parks by accumulation, as an excuse to study different architectural mechanisms in which its way of projecting is based. Such mechanisms already are part of a contemporaneous way of projecting. In addition, its analysis allows for the further understanding of some of the most interesting architectural phenomena that are being produced nowadays. The release of these mechanisms entails shedding a light to most of the proceedings and courses of the project that, because of the SANAA’s laconic way of designing, remain hidden most of the times and are often noticed through a slow and thorough look at the building. This document becomes then a work of research, where the Doctorate, as a detective, tracks SANAA’s projects, searching for those mechanisms that allow for truly defining the meaning of concepts such as maze, hierarchy, order, atmosphere and experience throughout Sejima’s and Nishizawa’s main horizontal space projects. Therefore, this thesis aims at shaping key references that constitute the imaginary universe of the Japanese study and that already are part of the contemporaneous architectural culture.

Estudio Multimodal de la Funcionalidad Cortical en ratones Transgénicos con Síndrome X Frágil y la modulación del dolor

El dolor es un síntoma frecuente en la práctica médica. En España, un estudio realizado en el año 2000 demostró que cada médico atiende un promedio de 181 pacientes con dolor por mes, la mayoría de ellos con dolor crónico moderado1. Del 7%-8% de la población europea está afectada y hasta el 5% puede ser grave2-3, se estima, que afecta a más de dos millones de españoles4. En la consulta de Atención Primaria, los pacientes con dolor neuropático tienen tasas de depresión mucho mayores 5-6-7. El dolor neuropático8 es el dolor causado por daño o enfermedad que afecta al sistema somato-sensorial, es un problema de salud pública con un alto coste laboral, debido a que existe cierto desconocimiento de sus singularidades, tanto de su diagnóstico como de su tratamiento, que al fallar, el dolor se perpetúa y se hace más rebelde a la hora de tratarlo, en la mayoría de las ocasiones pasa a ser crónico. Los mecanismos fisiopatológicos son evolutivos, se trata de un proceso progresivo e integrado que avanza si no recibe tratamiento, ocasionando graves repercusiones en la calidad de vida de los pacientes afectados9. De acuerdo a Prusiner (premio nobel de medicina 1997), en todas las enfermedades neurodegenerativas hay algún tipo de proceso anormal de la función neuronal. Las enfermedades neurodegenerativas son la consecuencia de anormalidades en el proceso de ciertas proteínas que intervienen en el ciclo celular, por lo tanto da lugar al cúmulo de las mismas en las neuronas o en sus proximidades, disminuyendo o anulando sus funciones, como la enfermedad de Alzheimer y el mismo SXF. La proteína FMRP (Fragile Mental Retardation Protein), esencial para el desarrollo cognitivo normal, ha sido relacionada con la vía piramidal del dolor10-11-12. El Síndrome de X Frágil13-14 (SXF), se debe a la mutación del Gen (FMR-1). Como consecuencia de la mutación, el gen se inactiva y no puede realizar la función de sintetizar la proteína FMRP. Por su incidencia se le considera la primera causa de Deficiencia Mental Hereditaria sólo superada por el Síndrome de Down. La electroencefalografía (EEG) es el registro de la actividad bioeléctrica cerebral que ha traído el desarrollo diario de los estudios clínicos y experimentales para el descubrimiento, diagnóstico y tratamiento de un gran número de anormalidades neurológicas y fisiológicas del cerebro y el resto del sistema nervioso central (SNC) incluyendo el dolor. El objetivo de la presente investigación es por medio de un estudio multimodal, desarrollar nuevas formas de presentación diagnóstica mediante técnicas avanzadas de procesado de señal y de imagen, determinando así los vínculos entre las evaluaciones cognitivas y su correlación anatómica con la modulación al dolor presente en patologías relacionadas con proteína FMRP. Utilizando técnicas biomédicas (funcionalestructural) para su caracterización. Para llevar a cabo esta tarea hemos utilizado el modelo animal de ratón. Nuestros resultados en este estudio multimodal demuestran que hay alteraciones en las vías de dolor en el modelo animal FMR1-KO, en concreto en la modulación encefálica (dolor neuropático), los datos se basan en los resultados del estudio estructural (imagen histología), funcional (EEG) y en pruebas de comportamiento (Laberinto de Barnes). En la Histología se muestra una clara asimetría estructural en el modelo FMR1 KO con respecto al control WT, donde el hemisferio Izquierdo tiene mayor densidad de masa neuronal en KO hembras 56.7%-60.8%, machos 58.3%-61%, en WT hembras 62.7%-62.4%, machos 55%-56.2%, hemisferio derecho-izquierdo respectivamente, esto refleja una correlación entre hemisferios muy baja en los sujetos KO (~50%) con respecto a los control WT (~90%). Se encontró correlación significativa entre las pruebas de memoria a largo plazo con respecto a la asimetría hemisférica (r = -0.48, corregido <0,05). En el estudio de comportamiento también hay diferencias, los sujetos WT tuvieron 22% un de rendimiento en la memoria a largo plazo, mientras que en los machos hay deterioro de memoria de un 28% que se corresponden con la patología en humanos. En los resultados de EEG estudiados en el hemisferio izquierdo, en el área de la corteza insular, encuentran que la latencia de la respuesta al potencial evocado es menor (22vs32 15vs96seg), la intensidad de la señal es mayor para los sujetos experimentales FMR1 KO frente a los sujetos control, esto es muy significativo dados los resultados en la histología (140vs129 145vs142 mv). Este estudio multimodal corrobora que las manifestaciones clínicas del SXF son variables dependientes de la edad y el sexo. Hemos podido corroborar en el modelo animal que en la etapa de adulto, los varones con SXF comienzan a desarrollar problemas en el desempeño de tareas que requieren la puesta en marcha de la función ejecutiva central de la memoria de trabajo (almacenamiento temporal). En el análisis del comportamiento es difícil llegar a una conclusión objetiva, se necesitan más estudios en diferentes etapas de la vida corroborados con resultados histológicos. Los avances logrados en los últimos años en su estudio han sido muy positivos, de tal modo que se están abriendo nuevas vías de investigación en un conjunto de procesos que representan un gran desafío a problemas médicos, asistenciales, sociales y económicos a los que se enfrentan los principales países desarrollados, con un aumento masivo de las expectativas de vida y de calidad. Las herramientas utilizadas en el campo de las neurociencias nos ofrecen grandes posibilidades para el desarrollo de estrategias que permitan ser utilizadas en el área de la educación, investigación y desarrollo. La genética determina la estructura del cerebro y nuestra investigación comprueba que la ausencia de FMRP también podría estar implicada en la modulación del dolor como parte de su expresión patológica siendo el modelo animal un punto importante en la investigación científica fundamental para entender el desarrollo de anormalidades en el cerebro. ABSTRACT Pain is a common symptom in medical practice. In Spain, a study conducted in 2000 each medical professional treats an average of 181 patients with pain per month, most of them with chronic moderate pain. 7% -8% of the European population is affected and up to 5% can be serious, it is estimated to affect more than two million people in Spain. In Primary Care, patients with neuropathic pain have much higher rates of depression. Neuropathic pain is caused by damage or disease affecting the somatosensory system, is a public health problem with high labor costs, there are relatively unfamiliar with the peculiarities in diagnosis and treatment, failing that, the pain is perpetuated and becomes rebellious to treat, in most cases becomes chronic. The pathophysiological mechanisms are evolutionary, its a progressive, if untreated, causing severe impact on the quality of life of affected patients. According to Prusiner (Nobel Prize for Medicine 1997), all neurodegenerative diseases there is some abnormal process of neuronal function. Neurodegenerative diseases are the result of abnormalities in the process of certain proteins involved in the cell cycle, reducing or canceling its features such as Alzheimer's disease and FXS. FMRP (Fragile Mental Retardation Protein), is essential for normal cognitive development, and has been linked to the pyramidal tract pain. Fragile X Syndrome (FXS), is due to mutation of the gene (FMR-1). As a consequence of the mutation, the gene is inactivated and can not perform the function of FMRP synthesize. For its incidence is considered the leading cause of Mental Deficiency Hereditary second only to Down Syndrome. Electroencephalography (EEG) is the recording of bioelectrical brain activity, is a advancement of clinical and experimental studies for the detection, diagnosis and treatment of many neurological and physiological abnormalities of the brain and the central nervous system, including pain. The objective of this research is a multimodal study, is the development of new forms of presentation using advanced diagnostic techniques of signal processing and image, to determine the links between cognitive evaluations and anatomic correlation with pain modulation to this protein FMRP-related pathologies. To accomplish this task have used the mouse model. Our results in this study show alterations in multimodal pain pathways in FMR1-KO in brain modulation (neuropathic pain), the data are based on the results of the structural study (histology image), functional (EEG) testing and behavior (Barnes maze). Histology In structural asymmetry shown in FMR1 KO model versus WT control, the left hemisphere is greater density of neuronal mass (KO females 56.7% -60.8%, 58.3% -61% males, females 62.7% -62.4 WT %, males 55% -56.2%), respectively right-left hemisphere, this reflects a very low correlation between hemispheres in KO (~ 50%) subjects compared to WT (~ 90%) control. Significant correlation was found between tests of long-term memory with respect to hemispheric asymmetry (r = -0.48, corrected <0.05). In the memory test there are differences too, the WT subjects had 22% yield in long-term memory, in males there memory impairment 28% corresponding to the condition in humans. The results of EEG studied in the left hemisphere, in insular cortex area, we found that the latency of the response evoked potential is lower (22vs32 15vs96seg), the signal strength is higher for the experimental subjects versus FMR1 KO control subjects, this is very significant given the results on histology (140vs129 145vs142 mv). This multimodal study confirms that the clinical manifestations of FXS are dependent variables of age and sex. We have been able to corroborate in the animal model in the adult stage, males with FXS begin developing problems in the performance of tasks that require the implementation of the central executive function of working memory (temporary storage). In behavior analysis is difficult to reach an objective conclusion, more studies are needed in different life stages corroborated with histologic findings. Advances in recent years were very positive, being opened new lines of research that represent a great challenge to physicians, health care, social and economic problems facing the major developed countries, with a massive increase in life expectancy and quality. The tools used in the field of neuroscience offer us great opportunities for the development of strategies to be used in the area of education, research and development. Genetics determines the structure of the brain and our research found that the absence of FMRP might also be involved in the modulation of pain as part of their pathological expression being an important animal model in basic scientific research to understand the development of abnormalities in brain.

Glutamate infused posttraining into the hippocampus or caudate-putamen differentially strengthens place and response learning

A cross-maze task that can be acquired through either place or response learning was used to examine the hypothesis that posttraining neurochemical manipulation of the hippocampus or caudate-putamen can bias an animal toward the use of a specific memory system. Male Long-Evans rats received four trials per day for 7 days, a probe trial on day 8, further training on days 9–15, and an additional probe trial on day 16. Training occurred in a cross-maze task in which rats started from a consistent start-box (south), and obtained food from a consistent goal-arm (west). On days 4–6 of training, rats received posttraining intrahippocampal (1 μg/0.5 μl) or intracaudate (2 μg/0.5 μl) injections of either glutamate or saline (0.5 μl). On days 8 and 16, a probe trial was given in which rats were placed in a novel start-box (north). Rats selecting the west goal-arm were designated “place” learners, and those selecting the east goal-arm were designated “response” learners. Saline-treated rats predominantly displayed place learning on day 8 and response learning on day 16, indicating a shift in control of learned behavior with extended training. Rats receiving intrahippocampal injections of glutamate predominantly displayed place learning on days 8 and 16, indicating that manipulation of the hippocampus produced a blockade of the shift to response learning. Rats receiving intracaudate injections of glutamate displayed response learning on days 8 and 16, indicating an accelerated shift to response learning. The findings suggest that posttraining intracerebral glutamate infusions can (i) modulate the distinct memory processes mediated by the hippocampus and caudate-putamen and (ii) bias the brain toward the use of a specific memory system to control learned behavior and thereby influence the timing of the switch from the use of cognitive memory to habit learning to guide behavior.

Late memory-related genes in the hippocampus revealed by RNA fingerprinting

Although long-term memory is thought to require a cellular program of gene expression and increased protein synthesis, the identity of proteins critical for associative memory is largely unknown. We used RNA fingerprinting to identify candidate memory-related genes (MRGs), which were up-regulated in the hippocampus of water maze-trained rats, a brain area that is critically involved in spatial learning. Two of the original 10 candidate genes implicated by RNA fingerprinting, the rat homolog of the ryanodine receptor type-2 and glutamate dehydrogenase (EC 1.4.1.3), were further investigated by Northern blot analysis, reverse transcription–PCR, and in situ hybridization and confirmed as MRGs with distinct temporal and regional expression. Successive RNA screening as illustrated here may help to reveal a spectrum of MRGs as they appear in distinct domains of memory storage.

Substitution of a mutant α2a-adrenergic receptor via “hit and run” gene targeting reveals the role of this subtype in sedative, analgesic, and anesthetic-sparing responses in vivo

Norepinephrine contributes to antinociceptive, sedative, and sympatholytic responses in vivo, and α2 adrenergic receptor (α2AR) agonists are used clinically to mimic these effects. Lack of subtype-specific agonists has prevented elucidation of the role that each α2AR subtype (α2A, α2B, and α2C) plays in these central effects. Here we demonstrate that α2AR agonist-elicited sedative, anesthetic-sparing, and analgesic responses are lost in a mouse line expressing a subtly mutated α2AAR, D79N α2AAR, created by two-step homologous recombination. These functional changes are accompanied by failure of the D79N α2AAR to inhibit voltage-gated Ca2+ currents and spontaneous neuronal firing, a measure of K+ current activation. These results provide definitive evidence that the α2AAR subtype is the primary mediator of clinically important central actions of α2AR agonists and suggest that the D79N α2AAR mouse may serve as a model for exploring other possible α2AAR functions in vivo.

Running enhances neurogenesis, learning, and long-term potentiation in mice

Running increases neurogenesis in the dentate gyrus of the hippocampus, a brain structure that is important for memory function. Consequently, spatial learning and long-term potentiation (LTP) were tested in groups of mice housed either with a running wheel (runners) or under standard conditions (controls). Mice were injected with bromodeoxyuridine to label dividing cells and trained in the Morris water maze. LTP was studied in the dentate gyrus and area CA1 in hippocampal slices from these mice. Running improved water maze performance, increased bromodeoxyuridine-positive cell numbers, and selectively enhanced dentate gyrus LTP. Our results indicate that physical activity can regulate hippocampal neurogenesis, synaptic plasticity, and learning.

Basolateral amygdala is not critical for cognitive memory of contextual fear conditioning

Evidence that lesions of the basolateral amygdala complex (BLC) impair memory for fear conditioning in rats, measured by lack of “freezing” behavior in the presence of cues previously paired with footshocks, has suggested that the BLC may be a critical locus for the memory of fear conditioning. However, evidence that BLC lesions may impair unlearned as well as conditioned freezing makes it difficult to interpret the findings of studies assessing conditioned fear with freezing. The present study investigated whether such lesions prevent the expression of several measures of memory for contextual fear conditioning in addition to freezing. On day 1, rats with sham lesions or BLC lesions explored a Y maze. The BLC-lesioned rats (BLC rats) displayed a greater exploratory activity. On day 2, each of the rats was placed in the “shock” arm of the maze, and all of the sham and half of the BLC rats received footshocks. A 24-hr retention test assessed the freezing, time spent per arm, entries per arm, and initial entry into the shock arm. As previously reported, shocked BLC rats displayed little freezing. However, the other measures indicated that the shocked BLC rats remembered the fear conditioning. They entered less readily and less often and spent less time in the shock arm than did the control nonshocked BLC rats. Compared with the sham rats, the shocked BLC rats entered more quickly and more often and spent more time in the shock arm. These findings indicate that an intact BLC is not essential for the formation and expression of long-term cognitive/explicit memory of contextual fear conditioning.

Perturbed dentate gyrus function in serotonin 5-HT2C receptor mutant mice

Serotonin systems have been implicated in the regulation of hippocampal function. Serotonin 5-HT2C receptors are widely expressed throughout the hippocampal formation, and these receptors have been proposed to modulate synaptic plasticity in the visual cortex. To assess the contribution of 5-HT2C receptors to the serotonergic regulation of hippocampal function, mice with a targeted 5-HT2C-receptor gene mutation were examined. An examination of long-term potentiation at each of four principal regions of the hippocampal formation revealed a selective impairment restricted to medial perforant path–dentate gyrus synapses of mutant mice. This deficit was accompanied by abnormal performance in behavioral assays associated with dentate gyrus function. 5-HT2C receptor mutants exhibited abnormal performance in the Morris water maze assay of spatial learning and reduced aversion to a novel environment. These deficits were selective and were not associated with a generalized learning deficit or with an impairment in the discrimination of spatial context. These results indicate that a genetic perturbation of serotonin receptor function can modulate dentate gyrus plasticity and that plasticity in this structure may contribute to neural mechanisms underlying hippocampus-dependent behaviors.

Memory and long-term potentiation (LTP) dissociated: Normal spatial memory despite CA1 LTP elimination with Kv1.4 antisense

Long-term potentiation (LTP) in the hippocampal slice preparation has been proposed as an in vitro model for long-term memory. However, correlation of LTP with memory in living animals has been difficult to demonstrate. Furthermore, in the last few years evidence has accumulated that dissociate the two. Because potassium channels might determine the weight of synapses in networks, we studied the role of Kv1.4, a presynaptic A-type voltage-dependent K+ channel, in both memory and LTP. Reverse transcription–PCR and Western blot analysis with specific antibodies showed that antisense oligodeoxyribonucleotide to Kv1.4 microinjected intraventricularly into rat brains obstructed hippocampal Kv1.4 mRNA, “knocking down” the protein in the hippocampus. This antisense knockdown had no effect on rat spatial maze learning, memory, or exploratory behavior, but eliminated both early- and late-phase LTP and reduced paired-pulse facilitation (a presynaptic effect) in CA1 pyramidal neurons without affecting dentate gyrus LTP. This presynaptic Kv1.4 knockdown together with previous postsynaptic Kv1.1 knockdown demonstrates that CA1 LTP is neither necessary nor sufficient for rat spatial memory.

Elevated anxiety and antidepressant-like responses in serotonin 5-HT1A receptor mutant mice

The brain serotonin (5-hydroxytryptamine; 5-HT) system is a powerful modulator of emotional processes and a target of medications used in the treatment of psychiatric disorders. To evaluate the contribution of serotonin 5-HT1A receptors to the regulation of these processes, we have used gene-targeting technology to generate 5-HT1A receptor-mutant mice. These animals lack functional 5-HT1A receptors as indicated by receptor autoradiography and by resistance to the hypothermic effects of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). Homozygous mutants display a consistent pattern of responses indicative of elevated anxiety levels in open-field, elevated-zero maze, and novel-object assays. Moreover, they exhibit antidepressant-like responses in a tail-suspension assay. These results indicate that the targeted disruption of the 5-HT1A receptor gene leads to heritable perturbations in the serotonergic regulation of emotional state. 5-HT1A receptor-null mutant mice have potential as a model for investigating mechanisms through which serotonergic systems modulate affective state and mediate the actions of psychiatric drugs.

Orphanin FQ acts as an anxiolytic to attenuate behavioral responses to stress

Orphanin FQ (OFQ, Nociceptin) is a recently discovered 17-amino acid neuropeptide that is structurally related to the opioid peptides but does not bind opioid receptors. OFQ has been proposed to act as an anti-opioid peptide, but its widespread sites of action in the brain suggest that it may have more general functions. Here we show that OFQ plays an important role in higher brain functions because it can act as an anxiolytic to attenuate the behavioral inhibition of animals acutely exposed to stressful/anxiogenic environmental conditions. OFQ anxiolytic-like effects were consistent across several behavioral paradigms generating different types of anxiety states in animals (light-dark preference, elevated plus-maze, exploratory behavior of an unfamiliar environment, pharmacological anxiogenesis, operant conflict) and were observed at low nonsedating doses (0.1–3 nmol, intracerebroventricular). Like conventional anxiolytics, OFQ interfered with regular sensorimotor function at high doses (>3 nmol). Our results show that an important role of OFQ is to act as an endogenous regulator of acute anxiety responses. OFQ, probably in concert with other major neuropeptides, exerts a modulatory role on the central integration of stressful stimuli and, thereby, may modulate anxiety states generated by acute stress.