PSA-NCAM is expressed in immature, but not recently generated, neurons in the adult cat cerebral cortex layer II

Neuronal production persists during adulthood in the dentate gyrus and the olfactory bulb, where substantial numbers of immature neurons can be found. These cells can also be found in the paleocortex layer II of adult rodents, but in this case most of them have been generated during embryogenesis. Recent reports have described the presence of similar cells, with a wider distribution, in the cerebral cortex of adult cats and primates and have suggested that they may develop into interneurons. The objective of this study is to verify this hypothesis and to explore the origin of these immature neurons in adult cats. We have analyzed their distribution using immunohistochemical analysis of the polysialylated form of the neural cell adhesion molecule (PSA-NCAM) and their phenotype using markers of mature neurons and different interneuronal populations. Additionally, we have explored the origin of these cells administering 5′bromodeoxyuridine (5′BrdU) during adulthood. Immature neurons were widely dispersed in the cerebral cortex layers II and upper III, being specially abundant in the piriform and entorhinal cortices, in the ventral portions of the frontal and temporoparietal lobes, but relatively scarce in dorsal regions, such as the primary visual areas. Only a small fraction of PSA-NCAM expressing cells in layer II expressed the mature neuronal marker NeuN and virtually none of them expressed calcium binding proteins or neuropeptides. By contrast, most, if not all of these cells expressed the transcription factor Tbr-1, specifically expressed by pallium-derived principal neurons, but not CAMKII, a marker of mature excitatory neurons. Absence of PSA-NCAM/5'BrdU colocalization suggests that, as in rats, these cells were not generated during adulthood. Together, these results indicate that immature neurons in the adult cat cerebral cortex layer II are not recently generated and that they may differentiate into principal neurons.Ministerio de Ciencia e Innovación BFU2009-12284/BF

La Educación Ambiental como centro de interés a través de las actividades extraescolares: Propuesta didáctica

La motivación y la atención juegan un papel principal durante el proceso de aprendizaje. Según Decroly (1968), éstas solo están presentes cuando los temas propuestos son del agrado del alumnado. Por este motivo, el autor fue el primero en impulsar el concepto de Centros de interés, que promueven una enseñanza basada en los intereses del alumno. En este trabajo de final de grado profundizaremos en el modelo de Centros de interés y plantearemos una propuesta de intervención basada en éstos para alumnos de primer ciclo de primaria. En este caso se opta por usar la Educación Ambiental para dotar a los alumnos de un mayor desarrollo integral sobre los seres vivos y el entorno natural que les rodea

Polysialic Acid Is Required for Dopamine D2 Receptor-Mediated Plasticity Involving Inhibitory Circuits of the Rat Medial Prefrontal Cortex

Decreased expression of dopamine D2 receptors (D2R), dysfunction of inhibitory neurotransmission and impairments in the structure and connectivity of neurons in the medial prefrontal cortex (mPFC) are involved in the pathogenesis of schizophrenia and major depression, but the relationship between these changes remains unclear. The polysialylated form of the neural cell adhesion molecule (PSA-NCAM), a plasticity-related molecule, may serve as a link. This molecule is expressed in cortical interneurons and dopamine, via D2R, modulates its expression in parallel to that of proteins related to synapses and inhibitory neurotransmission, suggesting that D2R-targeted antipsychotics/antidepressants may act by affecting the plasticity of mPFC inhibitory circuits. To understand the role of PSA-NCAM in this plasticity, rats were chronically treated with a D2R agonist (PPHT) after cortical PSA depletion. PPHT-induced increases in GAD67 and synaptophysin (SYN) neuropil expression were blocked when PSA was previously removed, indicating a role for PSA-NCAM in this plasticity. The number of PSA-NCAM expressing interneuron somata also increased after PPHT treatment, but the percentages of these cells belonging to different interneuronal subpopulations did not change. Cortical pyramidal neurons did not express PSA-NCAM, but puncta co-expressing this molecule and parvalbumin could be found surrounding their somata. PPHT treatment increased the number of PSA-NCAM and parvalbumin expressing perisomatic puncta, but decreased the percentage of parvalbumin puncta that co-expressed SYN. PSA depletion did not block these effects on the perisomatic region, but increased further the number of parvalbumin expressing puncta and increased the percentage of puncta co-expressing SYN and parvalbumin, suggesting that the polysialylation of NCAM may regulate perisomatic inhibition of mPFC principal neurons. Summarizing, the present results indicate that dopamine acting on D2R influences structural plasticity of mPFC interneurons and point to PSA-NCAM as a key player in this remodeling

Chronic stress-induced alterations in amygdala responsiveness and behavior - modulation by trait anxiety and corticotropin-releasing factor systems

The basolateral nucleus of the amygdala (BLA) plays a key role in emotional arousal and anxiety, and expresses high levels of corticotropin-releasing factor receptor (CRFR)1. In rat brain slices, we have recently shown that afferent activation of the BLA is increased following application of exogenous corticotropin-releasing factor (CRF). Here we examined the impact of chronic unpredictable stress (CUS) on this effect of CRF and whether blockade of CRFR1 could prevent stress-induced changes in the electrophysiological response, the animal's behavior and in cell proliferation in the hippocampus. The behavior of the rats was monitored via a series of tests that formed part of the CUS. Electrophysiological measures of the BLA response to CRF, cell proliferation in the dentate gyrus and the expression of CRF and CRFR1 mRNA in amygdaloid nuclei were determined ex vivo after completion of the CUS. CRF-induced potentiation of afferent activation of the BLA was reduced in rats exposed to CUS, an effect that was inhibited by chronic antagonism of CRFR1. Furthermore, the reduction in BLA response to CRF was correlated with the anxiety trait of the animals, determined prior to initiation of the CUS. These results implicate CRFR1 in chronic stress-induced alterations in amygdala function and behavior. Furthermore, they show that CRFR1 antagonists can prevent changes induced by chronic stress, in particular in those animals that are highly anxiou

Corema album archaeobotanical remains in western Mediterranean basin. Assessing fruit consumption during Upper Palaeolithic in Cova de les Cendres (Alicante, Spain)

[EN] Information about plant gathering by Palaeolithic hunter-gatherers in Europe is scarce because of the problems of preservation of plant remains in archaeological sites and due to the lack of application of archaebotanical analysis in many of them. Botanical macroremains wood charcoal, seeds, fruits, leaves, etc. - provide information not only about palaeoeconomy of hunter-gatherers, but also about climate, landscape and vegetation dynamics. In Gravettian and Solutrean levels of Cova de les Cendres (Alicante, Spain), Corema album pyrenes (Empetraceae or crowberries family) have been identified. On the contrary, wood charcoal of this species has not been documented among the remains of firewood. This differential presence of plant organs, together with the nutritional value of its fruits, which is presented here, make us hypothesize the systematic gathering of C. album fruits for human consumption. They have a high content in vitamin C, as well as potassium, magnesium and copper. Corema album (camariria) is a unique species, nowadays in danger of extinction. Its main population is located on the Atlantic coast of Iberian Peninsula, but in 1996 a small population was discovered on the Mediterranean Iberian coast (Benidorm, Spain). Archaeobotanical data from Cova de les Cendres (Teulada-Moraira, Spain) presented here point to a larger population of camariria during Upper Palaeolithic on the coast of Alicante. The harsh climatic conditions of the Last Glacial Maximum during Solutrean period, with colder temperatures and aridity increase, could explain the reduction of the presence of C album remains until its absence in Magdalenian. The climatic amelioration during Upper Magdalenian did not mean the recovery of camariria population in the Moraira headland area. Probably, the rising of the sea level would affect them destroying its dune habitat. (C) 2019 Elsevier Ltd. All rights reserved.Archaeological research at Cova de les Cendres was funded by Spanish Ministerio de Ciencia e Innovacion (HAR2011-24878; CGL2012-34717; HAR2014-5267 degrees 1-P; HAR2017-85153/P) and by Generalitat Valenciana (Grant PROMETEOII/2013/016; PROMETEO/2017/060). Seed analyses were carried out as doctoral research at the Departament de Prehistoria, Arqueologia i Historia Antiga (Universitat de Valencia) with the financial support of an "Atraccio de Talent" of VLC-Campus predoctoral grant to C.M. Martinez-Varea. Thanks to the Donana Biological Reserve for having allowed us to use the Singular Technical Scientific Installation for the Corema sampling. Authors want to thank M. Macias from Universitat Politecnica de Valencia for software development to draw the charcoal diagram and Eva Arnau from Universitat de Valencia for 3D modeling.Martínez-Varea, CM.; Ferrer-Gallego, P.; Raigón Jiménez, MD.; Badal, E.; Ferrando-Pardo, I.; Laguna-Lumbreras, E.; Real, C.... (2019). 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Alteración en los circuitos inhibidores en corteza somatosensorial e hipocampo en el modelo murino de síndrome de Down Ts65Dn

El síndrome de Down, con una incidencia de uno de cada 1000 nacimientos vivos, es la alteración genética más común asociada con retraso mental. La trisomía del cromosoma 21 induce un fenotipo variable que presenta, entre otros, defectos cardíacos o desarrollo temprano de la enfermedad de Alzheimer pero cuyo único aspecto común es un cierto grado de retraso mental. El mecanismo que provoca este retraso no está totalmente elucidado. Existen evidencias que apuntan a defectos en la formación de redes neurales, alteraciones en el procesamiento de la información y/o defectos en la capacidad plástica del cerebro. A nivel celular se ha observado que los individuos con síndrome de Down presentan alteraciones en la morfología, densidad y distribución de espinas en las dendritas de las neuronas piramidales corticales, así como en las neuronas granulares y piramidales del hipocampo. Muchas de estas alteraciones se mantienen en los modelos murinos de síndrome de Down, entre ellos el más ampliamente utilizado es el ratón Ts65Dn que presenta una trisomía parcial del cromosoma 16 murino. Nuestra hipótesis es que el déficit observado en la arborización dendrítica en los individuos con síndrome de Down puede estar motivado por desregulación en el balance entre la excitación y la inhibición y por tanto encontrase relacionado con alteraciones en las neuronas inhibidoras en las regiones correspondientes y en su conexión con las neuronas principales. Por tanto, hemos caracterizado la expresión de marcadores sinápticos y de las diversas poblaciones de interneuronas en corteza somatosensorial e hipocampo en ratones Ts65Dn de 3 meses de edad utilizando técnicas inmunohistoquímicas y analizando la expresión mediante recuentos y densitometrías. Hemos observado un incremento en los contactos inhibidores totales en las dos regiones analizadas. Se observa un incremento en el número de neuronas inhibidoras, fundamentalmente aquellas que expresan la proteína ligante de calcio calretinina

Personality traits in rats predict vulnerability and resilience to developing stress-induced depression-like behaviors, HPA axis hyper-reactivity and brain changes in pERK1/2 activity

Emerging evidence indicates that certain behavioral traits, such as anxiety, are associated with the development of depression-like behaviors after exposure to chronic stress. However, single traits do not explain the wide variability in vulnerability to stress observed in outbred populations. We hypothesized that a combination of behavioral traits might provide a better characterization of an individual's vulnerability to prolonged stress. Here, we sought to determine whether the characterization of relevant behavioral traits in rats could aid in identifying individuals with different vulnerabilities to developing stress-induced depression-like behavioral alterations. We also investigated whether behavioral traits would be related to the development of alterations in the hypothalamic-pituitary-adrenal axis and in brain activity - as measured through phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) - in response to an acute stressor following either sub-chronic (2 weeks) or chronic (4 weeks) unpredictable stress (CUS). Sprague-Dawley rats were characterized using a battery of behavioral tasks, and three principal traits were identified: anxiety, exploration and activity. When combined, the first two traits were found to explain the variability in the stress responses. Our findings confirm the increased risk of animals with high anxiety developing certain depression-like behaviors (e.g., increased floating time in the forced swim test) when progressively exposed to stress. In contrast, the behavioral profile based on combined low anxiety and low exploration was resistant to alterations related to social behaviors, while the high anxiety and low exploration profile displayed a particularly vulnerable pattern of physiological and neurobiological responses after sub-chronic stress exposure. Our findings indicate important differences in animals' vulnerability and/or resilience to the effects of repeated stress, particularly during initial or intermediate levels of stress exposure, and they highlight that the behavioral inhibition profile of an animal provides a particular susceptibility to responding in a deleterious manner to stress

Upregulation of polysialylated neural cell adhesion molecule in the dorsal hippocampus after contextual fear conditioning is involved in long-term memory formation

The role of the hippocampus in pavlovian fear conditioning is controversial. Although lesion and pharmacological inactivation studies have suggested a key role for the dorsal hippocampus in contextual fear conditioning, the involvement of the ventral part is still uncertain. Likewise, the debate is open with regard to the putative implication of each hippocampal subdivision in fear conditioning to a discrete conditioned stimulus. We explored the potential existence of dissociations occurring in the dorsal versus ventral hippocampus at the cellular level while dealing with either contextual or cued fear conditioning and focused in a molecular "signature" linked to structural plasticity, the polysialylated form of the neural cell adhesion molecule (PSA-NCAM). We found an upregulation of PSA-NCAM expression in the dorsal (but not ventral) dentate gyrus at 24 h after contextual (but not tone) fear conditioning. Specific removal of PSA through microinfusion of the enzyme endoneuraminidase-N in the dorsal (but not ventral) hippocampus reduced freezing responses to the conditioned context. Therefore, we present evidence for a specific role of PSA-NCAM in the dorsal hippocampus in the plasticity processes occurring during consolidation of the context representation after "standard" contextual fear conditioning. Interestingly, we also found that exposing animals just to the context induced an activation of PSA-NCAM in both dorsal and ventral dentate gyrus. Altogether, these findings highlighting the distinctive occurrence of these neuroplastic processes in the dorsal hippocampus during the standard contextual fear-conditioning task enlighten the ongoing debate about the involvement of these hippocampal subdivisions in pavlovian fear conditionin

Synaptic connectivity of the cholinergic axons in the olfactory bulb of the cynomolgus monkey

The olfactory bulb (OB) of mammals receives cholinergic afferents from the horizontal limb of the diagonal band of Broca (HDB). At present, the synaptic connectivity of the cholinergic axons on the circuits of the OB has only been investigated in the rat. In this report, we analyze the synaptic connectivity of the cholinergic axons in the OB of the cynomolgus monkey (Macaca fascicularis). Our aim is to investigate whether the cholinergic innervation of the bulbar circuits is phylogenetically conserved between macrosmatic and microsmatic mammals. Our results demonstrate that the cholinergic axons form synaptic contacts on interneurons. In the glomerular layer, their main targets are the periglomerular cells, which receive axo-somatic and axo-dendritic synapses. In the inframitral region, their main targets are the granule cells, which receive synaptic contacts on their dendritic shafts and spines. Although the cholinergic boutons were frequently found in close vicinity of the dendrites of principal cells, we have not found synaptic contacts on them. From a comparative perspective, our data indicate that the synaptic connectivity of the cholinergic circuits is highly preserved in the OB of macrosmatic and microsmatic mammals

Alterations of perineuronal nets in the dorsolateral prefrontal cortex of neuropsychiatric patients

Background: Alterations in the structure and physiology of interneurons in the prefrontal cortex (PFC) are important factors in the etiopathology of different psychiatric disorders. Among the interneuronal subpopulations, parvalbumin (PV) expressing cells appear to be specially affected. Interestingly, during development and adulthood the connectivity of these interneurons is regulated by the presence of perineuronal nets (PNNs), specialized regions of the extracellular matrix, which are frequently surrounding PV expressing neurons. Previous reports have found anomalies in the density of PNNs in the PFC of schizophrenic patients. However, although some studies have described alterations in PNNs in some extracortical regions of bipolar disorder patients, there are no studies focusing on the prefrontocortical PNNs of bipolar or major depression patients. For this reason, we have analyzed the density of PNNs in post-mortem sections of the dorsolateral PFC (DLPFC) from the Stanley Neuropathology Consortium, which includes controls, schizophrenia, bipolar and major depression patients. Results: We have not observed differences in the distribution of PV+ cells or PNNs, or in the percentage of PV+ interneurons surrounded by PNNs. The density of PV+ interneurons was similar in all the experimental groups, but there was a significantly lower density of PNNs in the DLPFC of bipolar disorder patients and a tendency towards a decrease in schizophrenic patients. No differences were found when evaluating the density of PV+ cells surrounded by PNNs. Interestingly, when assessing the influence of demographic data, we found an inverse correlation between the density of PNNs and the presence of psychosis. Conclusions: The present results point to prefrontocortical PNNs and their role in the regulation of neuronal plasticity as putative players in the etiopathology of bipolar disorder and schizophrenia. Our findings also suggest a link between these specialized regions of the extracellular matrix and the presence of psychosis