Behavioral phenotyping of glutathione-deficient mice: Relevance to schizophrenia and bipolar disorder.

Redox-dysregulation represents a common pathogenic mechanism in schizophrenia (SZ) and bipolar disorder (BP). It may in part arise from a genetically compromised synthesis of glutathione (GSH), the major cellular antioxidant and redox-regulator. Allelic variants of the genes coding for the rate-limiting GSH synthesizing enzyme glutamate-cysteine-ligase modifier (GCLM) and/or catalytic (GCLC) subunit have been associated with SZ and BP. Using mice knockout (KO) for GCLM we have previously shown that impaired GSH synthesis is associated with morphological, functional and neurochemical anomalies similar to those in patients. Here we asked whether GSH deficit is also associated with SZ- and BP-relevant behavioral and cognitive anomalies. Accordingly, we subjected young adult GCLM-wildtype (WT), heterozygous and KO males to a battery of standard tests. Compared to WT, GCLM-KO mice displayed hyperlocomotion in the open field and forced swim test but normal activity in the home cage, suggesting that hyperlocomotion was selective to environmental novelty and mildly stressful situations. While spatial working memory and latent inhibition remained unaffected, KO mice showed a potentiated hyperlocomotor response to an acute amphetamine injection, impaired sensorymotor gating in the form of prepulse inhibition and altered social behavior compared to WT. These anomalies resemble important aspects of both SZ and the manic component of BP. As such our data support the notion that redox-dysregulation due to GSH deficit is implicated in both disorders. Moreover, our data propose the GCLM-KO mouse as a valuable model to study the behavioral and cognitive consequences of redox dysregulation in the context of psychiatric disease.

Spaced training facilitates long-term retention of place navigation in adult but not in adolescent rats

Young and adult Long Evans rats were tested in the water maze according to two different procedures: half of the subjects were given one session of four trials a day for 6 days, whereas the other subjects had the same amount of training massed in 1 day. For both conditions, a 14-day retention interval was then introduced to test long-term memory. This was followed by a four-trial reversal session. All groups showed a significant learning curve, but escape latencies were shorter for the adult than for the young rats, without differential effect of the training procedure. A first probe trial (PT1) confirmed similar accurate short-term retention in all the groups. But unimpaired long-term memory was only seen in the adult rats trained with the spaced procedure. The young rats trained over 1 day also showed some retention of the platform location after 14 days, but not the other two groups. Reversal acquisition of the new platform location was rapid in the four groups. These results indicate that although accurate short-term spatial memory in the water maze is seen after a 1-day massed training in both age groups, unimpaired long-term retention is only observed in adult rats trained with 24-h inter-session intervals.

Building hippocampal circuits to learn and remember: insights into the development of human memory

The hippocampal formation is essential for the processing of episodic memories for autobiographical events that happen in unique spatiotemporal contexts. Interestingly, before 2 years of age, children are unable to form or store episodic memories for recall later in life, a phenomenon known as infantile amnesia. From 2 to 7 years of age, there are fewer memories than predicted based on a forgetting function alone, a phenomenon known as childhood amnesia. Here, we discuss the postnatal maturation of the primate hippocampal formation with the goal of characterizing the development of the neurobiological substrates thought to subserve the emergence of episodic memory. Distinct regions, layers and cells of the hippocampal formation exhibit different profiles of structural and molecular development during early postnatal life. The protracted period of neuronal addition and maturation in the dentate gyrus is accompanied by the late maturation of specific layers in different hippocampal regions that are located downstream from the dentate gyrus, particularly CA3. In contrast, distinct layers in several hippocampal regions, particularly CA1, which receive direct projections from the entorhinal cortex, exhibit an early maturation. In addition, hippocampal regions that are more highly interconnected with subcortical structures, including the subiculum, presubiculum, parasubiculum and CA2, mature even earlier. These findings, together with our studies of the development of human spatial memory, support the hypothesis that the differential maturation of distinct hippocampal circuits might underlie the differential emergence of specific "hippocampus-dependent" memory processes, culminating in the emergence of episodic memory concomitant with the maturation of all hippocampal circuits.

Auditory cues support place navigation in rats when associated with a visual cue.

Rats, like other crepuscular animals, have excellent auditory capacities and they discriminate well between different sounds [Heffner HE, Heffner RS, Hearing in two cricetid rodents: wood rats (Neotoma floridana) and grasshopper mouse (Onychomys leucogaster). J Comp Psychol 1985;99(3):275-88]. However, most experimental literature concerning spatial orientation almost exclusively emphasizes the use of visual landmarks [Cressant A, Muller RU, Poucet B. Failure of centrally placed objects to control the firing fields of hippocampal place cells. J Neurosci 1997;17(7):2531-42; and Goodridge JP, Taube JS. Preferential use of the landmark navigational system by head direction cells in rats. Behav Neurosci 1995;109(1):49-61]. To address the important issue of whether rats are able to achieve a place navigation task relative to auditory beacons, we designed a place learning task in the water maze. We controlled cue availability by conducting the experiment in total darkness. Three auditory cues did not allow place navigation whereas three visual cues in the same positions did support place navigation. One auditory beacon directly associated with the goal location did not support taxon navigation (a beacon strategy allowing the animal to find the goal just by swimming toward the cue). Replacing the auditory beacons by one single visual beacon did support taxon navigation. A multimodal configuration of two auditory cues and one visual cue allowed correct place navigation. The deletion of the two auditory or of the one visual cue did disrupt the spatial performance. Thus rats can combine information from different sensory modalities to achieve a place navigation task. In particular, auditory cues support place navigation when associated with a visual one.

Postnatal intracerebroventricular administrations of NGF alter spatial memory in adulthood

The present work assessed the effects of intracerebroventricular injections (2x5 mg/2.5 ml) of recombined human nerve growth factor (rhNGF) at postnatal days 2 and 3 upon the development of spatial learning capacities in rats. The treated rats were trained at the age of 22 days to escape onto an invisible platform at a fixed position in space in a Morris navigation task. For half of the subjects, the training position was also cued, a procedure aimed at facilitating escape and reducing attention to the distant spatial cues. At the age of 2 months all the rats were retrained in the same task. Treatment effects were found in both immature and adult rats. The injection of NGF induced a slight alteration of the immature rats' performance. In contrast, a marked impairment of spatial abilities was shown in the 2-month-old rats. The most consistent effects were a significant increase in the escape latency and a decrease bias towards the training platform area during probe trials. The reduction of spatial memory was particularly marked if the subjects had been trained in a cued condition. Taken together, these experiments reveal that an acute pharmacological treatment that leads to transient modifications during early development might induce a behavioural change long after treatment. Thus, the development and the maintenance of an accurate spatial representation are tightly related to the development of brain structures that could be altered by precocious NGF administrations.

Post-switching beta synchronization reveals concomitant sensory reafferences and active inhibition processes

It is known that post-movement beta synchronization (PMBS) is involved both in active inhibition and in sensory reafferences processes. The aim of this study was examine the temporal and spatial dynamics of the PMBS involved during multi-limb coordination task. We investigated post-switching beta synchronization (assigned PMBS) using time-frequency and source estimations analyzes. Participants (n = 17) initiated an auditory-paced bimanual tapping. After a 1500 ms preparatory period, an imperative stimulus required to either selectively stop the left while maintaining the right unimanual tapping (Switch condition: SWIT) or to continue the bimanual tapping (Continue condition: CONT). PMBS significantly increased in SWIT compared to CONT with maximal difference within right central region in broad-band 14âeuro"30 Hz and within left central region in restricted-band 22âeuro"26 Hz. Source estimations localized these effects within right pre-frontal cortex and left parietal cortex, respectively. A negative correlation showed that participants with a low percentage of errors in SWIT had a large PMBS amplitude within right parietal and frontal cortices. This study shows for the first time simultaneous PMBS with distinct functions in different brain regions and frequency ranges. The left parietal PMBS restricted to 22âeuro"26 Hz could reflect the sensory reafferences of the right hand tapping disrupted by the switching. In contrast, the right pre-frontal PMBS in a broad-band 14âeuro"30 Hz is likely reflecting the active inhibition of the left hand stopped. Finally, correlations between behavioral performance and the magnitude of the PMBS suggest that beta oscillations can be viewed as a marker of successful active inhibition.

Adaptive changes in a radial maze task: Efficient selection of baited arms with reduced foraging in senescent hooded rats

Qualitative differences in strategy selection during foraging in a partially baited maze were assessed in young and old rats. The baited and non-baited arms were at a fixed position in space and marked by a specific olfactory cue. The senescent rats did more re-entries during the first four-trial block but were more rapid than the young rats in selecting the reinforced arms during the first visits. Dissociation between the olfactory spatial cue reference by rotating the maze revealed that only few old subjects relied on olfactory cues to select the baited arms and the remainder relied mainly on the visuo-spatial cues.

Successful new venturing process implemented by the founding entrepreneur: A case of Finnish sawmill industry

The fundamental purpose of this research is to emphasise a founding entrepreneur’s own role in the construction of a successful business story, with the focus being on the analysis of the entrepreneur’s activities. The theoretical section sheds light on the heterogeneous nature of existing performance research and, thereby, opens the way for the behavioural approach research of entrepreneurs in the field of new venture performance research. This research can be seen to be in line with the latest trends in entrepreneurship research, which question the applicability of different organisational theories in entrepreneurship research. For this reason, the founding entrepreneur has been chosen, instead of the company, to be the unit of analysis in this research in order to lighten the link in question while developing and refining new knowledge in the field of entrepreneurship. The empirical section of this research focuses on the entrepreneur’s own actions or behaviours that can be seen to be associated with the company’s success. Although some of these actions may resemble the strategic actions of a company as defined in strategic management literature, these actions taken by the entrepreneur themselves must be distinguished from the different organisational actions. Usually, an entrepreneur makes decisions rather independently, mainly on basis of their own intuition and prevailing market conditions, whereas organisational actions are very systematic, and each decision involves many different people. For this reason, an entrepreneur’s actions must be distinguished from organisational actions. In additional to different action paths, the empirical data collected for this research also offers almost unambiguous proof that the actions taken by an entrepreneur at the different stages of a company’s development do play a crucial role in the success of the companies studied in this research. In this way, it is possible to identify a significant link between the behavioural approach research of entrepreneurs and new venture performance research. Due to a lack of behavioural research into founding entrepreneurs, this research has utilised a qualitative (hermeneutic) research approach. The researcher strove to establish a particularly close connection with the entrepreneurs that were studied here and, thus, understand the actions taken at the different stages of their companies’ development as well as the motives and fundamental purposes of these actions. It would not have been possible to manage such profound data that focuses on causalities by using quantitative methods. In addition to interviews, this research used corporate histories of the companies for collecting some of the research data. These corporate histories can be considered excellent tools for the researcher to obtain a preliminary understanding and can, thereby, be seen to have laid the ground for more in-depth and diverse analyses.

El perfil criminal del asesino en serie colombiano desde la perspectiva psicodinámica. Una revisión de literatura

El objetivo de la presente investigación consiste en describir las características de un asesino en serie colombiano desde la perspectiva psicodinámica. En este sentido, el abordaje teórico realizado en este trabajo se compone inicialmente de una concepción de asesinos en serie, posteriormente se hace una revisión acerca de las bases biológicas y los factores sociales del homicida serial, igualmente, se explican tres teorías psicodinámicas a trabajar (Sigmund Freud y Erick Erickson). Finalmente, se hace mención dentro de la investigación a la comparación casuística de los asesinos en serie, teniendo en cuenta a cuatro asesinos en serie mediante el abordaje psicodinámico. Por otra parte, a nivel metodológico, el tipo de estudio realizado es descriptivo con un corte cualitativo y un diseño no experimental, basado en la revisión de fuentes bibliográficas. Como producto se pretende hacer una aproximación al perfil correspondiente de la personalidad de un asesino en serie colombiano mediante las teorías psicodinámicas.

Metodologías de valoración de empresas

La valoración de una empresa como sistema dinámico es bastante compleja, los diferentes modelos o métodos de valoración son una aproximación teórica y por consiguiente simplificadora de la realidad. Dichos modelos, se aproximan mediante supuestos o premisas estadísticas que nos permiten hacer dicha simplificación, ejemplos de estos, son el comportamiento del inversionista o la eficiencia del mercado. Bajo el marco de un mercado emergente, este proceso presenta de indistinta forma retos paracualquier método de valoración, dado a que el mercado no obedece a los paradigmas tradicionales. Lo anterior hace referencia a que la valoración es aún más compleja, dado que los inversionistas se enfrentan a mayores riesgos y obstáculos. Así mismo, a medida que las economías se globalizan y el capital es más móvil, la valoración tomaráaún más importancia en el contexto citado. Este trabajo de gradopretende recopilar y analizar los diferentes métodos de valoración, además de identificar y aplicar aquellos que se reconocen como “buenas prácticas”. Este proceso se llevó a cabo para una de las empresas más importantes de Colombia, donde fundamentalmente se consideró el contexto de mercado emergente y específicamente el sector petrolero, como criterios para la aplicación del tradicional DCF y el práctico R&V.

El desarrollo del mercado bursátil en Colombia y en chile a partir de la conformación de portafolios de inversión de moneda extranjera

Realizar una comparación entre el mercado bursátil colombiano y el chileno, a través de un paralelo histórico teniendo en cuenta las legislaciones que rigen dichos mercados y la inversión extranjera en portafolios de inversión, con el fin de determinar por qué el mercado colombiano no se ha desarrollado tan positivamente como lo ha hecho el chileno y definir los posibles mecanismos y políticas adecuadas que deban implementarse para generar ese desarrollo.

Efectos en los grandes procesadores lecheros colombianos con la entrada en vigencia del tratado de libre comercio con la unión europea

La economía mundial ha presentado una tendencia hacia la globalización y la integración económica; este comportamiento ha influenciado significativamente la economía Colombiana en los últimos años, promoviendo los lazos comerciales con diferentes economías a nivel mundial; esto con el objetivo de fortalecer la actividad económica tanto interna como externamente, buscando nuevas oportunidades que le permitan un crecimiento económico perdurable, a través de la inversión extranjera directa, la investigación y desarrollo, innovación tecnológica, mano de obra calificada, entre otros. Continuando esta tendencia Colombia inició un proceso de negociación de un Tratado de Libre Comercio con la Unión Europea en el año 2012, el cual culminó con éxito firmándose el 31 de Julio del 2013, mediante el decreto 1636, donde Colombia y la Unión Europea por libre albedrio se comprometieron a cumplir con todos los puntos pactados dentro del tratado. Con el objetivo de generar un diagnóstico del sub-sector lechero, se analizó la situación actual de la economía Colombiana frente a la Unión Europea, vista desde la productividad y la competitividad que se presenta en cada una de estas economías, para determinar las oportunidades o las amenazas que podría representar el tratado de libre comercio con dicho grupo económico pero específicamente concentrándose en la industria procesadora de productos lácteos. Del diagnóstico comparativo se encontró que existen grandes asimetrías entre la industria procesadora de productos lácteos en Colombia frente a la misma de la Unión Europea (UE). Por último se realizó el análisis de los factores internos de las empresas a través de la Matriz de Evaluación de Factores Internos (MEFI), indicador que permite identificar la debilidad o fortaleza dentro de las empresas de acuerdo a la valoración de las características de cada una. Por otro lado, a través de la matriz DOFA se analizaron las debilidades, oportunidades, fortalezas y amenazas de las empresas; de acuerdo a los resultados de ambas matrices se plantearon recomendaciones que podrán ser aplicadas dentro de las empresas objeto de estudio.

Activation of G-protein-coupled receptor 30 is sufficient to enhance spatial recognition memory in ovariectomized rats

In ovariectomized rats, administration of estradiol, or selective estrogen receptor agonists that activate either the alpha or beta isoforms, have been shown to enhance spatial cognition on a variety of learning and memory tasks, including those that capitalize on the preference of rats to seek out novelty. Although the effects of the putative estrogen G-protein-coupled receptor 30 (GPR30) on hippocampus-based tasks have been reported using food-motivated tasks, the effects of activation of GPR30 receptors on tasks that depend on the preference of rats to seek out spatial novelty remain to be determined. Therefore, the aim of the current study was to determine if short-term treatment of ovariectomized rats with G-1, an agonist for GPR30, would mimic the effects on spatial recognition memory observed following short-term estradiol treatment. In Experiment 1, ovariectomized rats treated with a low dose (1mug) of estradiol 48h and 24h prior to the information trial of a Y-maze task exhibited a preference for the arm associated with the novel environment on the retention trial conducted 48h later. In Experiment 2, treatment of ovariectomized rats with G-1 (25mug) 48h and 24h prior to the information trial of a Y-maze task resulted in a greater preference for the arm associated with the novel environment on the retention trial. Collectively, the results indicated that short-term treatment of ovariectomized rats with a GPR30 agonist was sufficient to enhance spatial recognition memory, an effect that also occurred following short-term treatment with a low dose of estradiol.

Investigation of the hypothalamic defensive system in the mouse

The hypothalamus plays especially important roles in various endocrine, autonomic, and behavioral responses that guarantee the survival of both the individual and the species. In the rat, a distinct hypothalamic defensive circuit has been defined as critical for integrating predatory threats, raising an important question as to whether this concept could be applied to other prey species. To start addressing this matter, in the present study, we investigated, in another prey species (the mouse), the pattern of hypothalamic Fos immunoreactivity in response to exposure to a predator (a rat, using the Rat Exposure Test). During rat exposure, mice remained concealed in the home chamber for a longer period of time and increased freezing and risk assessment activity. We were able to show that the mouse and the rat present a similar pattern of hypothalamic activation in response to a predator. Of particular note, similar to what has been described for the rat, we observed in the mouse that predator exposure induces a striking activation in the elements of the medial hypothalamic defensive system, namely, the anterior hypothalamic nucleus, the dorsomedial part of the ventromedial hypothalamic nucleus and the dorsal premammillary nucleus. Moreover, as described for the rat, predator-exposed mice also presented increased Fos levels in the autonomic and parvicellular parts of the paraventricular hypothalamic nucleus, lateral preoptic area and subfornical region of the lateral hypothalamic area. In conclusion, the present data give further support to the concept that a specific hypothalamic defensive circuit should be preserved across different prey species. (C) 2008 Elsevier B.V. All rights reserved.