Corticogenesis and folding process of the neopallium in the South American plains vizcacha, Lagostomus maximus.

The plains vizcacha, Lagostomus maximus, is a precocial hystricomorph rodent with a gyrencephalic brain. This work aimed to perform a time-lapse analysis of the embryonic brain cortical development in the plains vizcacha to establish a species-specific temporal window for corticogenesis and the gyrencephaly onset. Additionally, a comparative examination with evolutionarily related rodents was conducted. Embryos from 40 embryonic days (ED) until the end of pregnancy ( ∼ $\sim $ 154 ED) were evaluated. The neuroanatomical examination determined transverse sulci at 80 ED and rostral lateral and caudal intraparietal sulci around 95 ED. Histological examination of corticogenesis showed emergence of the subplate at 43 ED and expansion of the subventricular zone (SVZ) and its division into inner and outer SVZs around 54 ED. The neocortical layers formation followed an inside-to-outside spatiotemporal gradient beginning with the emergence of layers VI and V at 68 ED and establishing the final six neocortical layers around 100 ED. A progressive increment of gyrencephalization index (GI) from 1.005 ± 0.003 around 70 ED, which reflects a smooth cortex, up to 1.07 ± 0.009 at the end of gestation, reflecting a gyrencephalic neuroanatomy, was determined. Contrarily, the minimum cortical thickness (MCT) progressively decreased from 61 ED up to the end of gestation. These results show that the decrease in the cortical thickness, which enables the onset of neocortical invaginations, occurs together with the expansion and subdivision of the SVZ. The temporal comparison of corticogenesis in plains vizcacha with that in relative species reflects a prenatal long process compared with other rodents that may give an evolutionary advantage to L. maximus as a precocial species.

Metabolic dysfunction induced by HFD + L-NAME preferentially affects hippocampal mitochondria, impacting spatial memory in rats.

High-fat diet-induced metabolic changes are not restricted to the onset of cardiovascular diseases, but also include effects on brain functions related to learning and memory. This study aimed to evaluate mitochondrial markers and function, as well as cognitive function, in a rat model of metabolic dysfunction. Eight-week-old male Wistar rats were subjected to either a control diet or a two-hit protocol combining a high fat diet (HFD) with the nitric oxide synthase inhibitor L-NAME in the drinking water. HFD plus L-NAME induced obesity, hypertension, and increased serum cholesterol. These rats exhibited bioenergetic dysfunction in the hippocampus, characterized by decreased oxygen (O2) consumption related to ATP production, with no changes in H2O2 production. Furthermore, OPA1 protein expression was upregulated in the hippocampus of HFD + L-NAME rats, with no alterations in other morphology-related proteins. Consistently, HFD + L-NAME rats showed disruption of performance in the Morris Water Maze Reference Memory test. The neocortex did not exhibit either bioenergetic changes or alterations in H2O2 production. Calcium uptake rate and retention capacity in the neocortex of HFD + L-NAME rats were not altered. Our results indicate that hippocampal mitochondrial bioenergetic function is disturbed in rats exposed to a HFD plus L-NAME, thus disrupting spatial learning, whereas neocortical function remains unaffected.

Transcranial Focal Electric Stimulation Avoids P-Glycoprotein Over-Expression during Electrical Amygdala Kindling and Delays Epileptogenesis in Rats.

Recent evidence suggests that P-glycoprotein (P-gp) overexpression mediates hyperexcitability and is associated with epileptogenesis. Transcranial focal electrical stimulation (TFS) delays epileptogenesis and inhibits P-gp overexpression after a generalized seizure. Here, first we measured P-gp expression during epileptogenesis and second, we assessed if TFS antiepileptogenic effect was related with P-gp overexpression avoidance. Male Wistar rats were implanted in right basolateral amygdala and stimulated daily for electrical amygdala kindling (EAK), P-gp expression was assessed during epileptogenesis in relevant brain areas. Stage I group showed 85% increase in P-gp in ipsilateral hippocampus (p < 0.001). Stage III group presented 58% and 57% increase in P-gp in both hippocampi (p < 0.05). Kindled group had 92% and 90% increase in P-gp in both hippocampi (p < 0.01), and 93% and 143% increase in both neocortices (p < 0.01). For the second experiment, TFS was administrated daily after each EAK stimulation for 20 days and P-gp concentration was assessed. No changes were found in the TFS group (p > 0.05). Kindled group showed 132% and 138% increase in P-gp in both hippocampi (p < 0.001) and 51% and 92% increase in both cortices (p < 0.001). Kindled + TFS group presented no changes (p > 0.05). Our experiments revealed that progression of EAK is associated with increased P-gp expression. These changes are structure-specific and dependent on seizure severity. EAK-induced P-gp overexpression would be associated with neuronal hyperexcitability and thus, epileptogenesis. P-gp could be a novel therapeutical target to avoid epileptogenesis. In accordance with this, TFS inhibited P-gp overexpression and interfered with EAK. An important limitation of the present study is that P-gp neuronal expression was not evaluated under the different experimental conditions. Future studies should be carried out to determine P-gp neuronal overexpression in hyperexcitable networks during epileptogenesis. The TFS-induced lessening of P-gp overexpression could be a novel therapeutical strategy to avoid epileptogenesis in high-risk patients.

Amygdala and hippocampus dialogue with neocortex during human sleep and wakefulness.

ABSTRACT: Previous studies have described synchronic electroencephalographic (EEG) patterns of the background activity that is characteristic of several vigilance states. STUDY OBJECTIVES: To explore whether the background synchronous activity of the amygdala-hippocampal-neocortical circuit is modified during sleep in the delta, theta, alpha, sigma, beta, and gamma bands characteristic of each sleep state. METHODS: By simultaneously recording intracranial and noninvasive scalp EEG (10-20 system) in epileptic patients who were candidates for neurosurgery, we explored synchronous activity among the amygdala, hippocampus, and neocortex during wakefulness (W), Non-Rapid Eye Movement (NREM), and Rapid-Eye Movement (REM) sleep. RESULTS: Our findings reveal that hippocampal-cortical synchrony in the sleep spindle frequencies was spread across the cortex and was higher during NREM versus W and REM, whereas the amygdala showed punctual higher synchronization with the temporal lobe. Contrary to expectations, delta synchrony between the amygdala and frontal lobe and between the hippocampus and temporal lobe was higher during REM than NREM. Gamma and alpha showed higher synchrony between limbic structures and the neocortex during wakefulness versus sleep, while synchrony among deep structures showed a mixed pattern. On the one hand, amygdala-hippocampal synchrony resembled cortical activity (i.e. higher gamma and alpha synchrony in W); on the other, it showed its own pattern in slow frequency oscillations. CONCLUSIONS: This is the first study to depict diverse patterns of synchronic interaction among the frequency bands during distinct vigilance states in a broad human brain circuit with direct anatomical and functional connections that play a crucial role in emotional processes and memory.

Long-Range GABAergic Projections of Cortical Origin in Brain Function.

The study of long-range GABAergic projections has traditionally been focused on those with subcortical origin. In the last few years, cortical GABAergic neurons have been shown to not only mediate local inhibition, but also extend long-range axons to remote cortical and subcortical areas. In this review, we delineate the different types of long-range GABAergic neurons (LRGNs) that have been reported to arise from the hippocampus and neocortex, paying attention to the anatomical and functional circuits they form to understand their role in behavior. Although cortical LRGNs are similar to their interneuron and subcortical counterparts, they comprise distinct populations that show specific patterns of cortico-cortical and cortico-fugal connectivity. Functionally, cortical LRGNs likely induce timed disinhibition in target regions to synchronize network activity. Thus, LRGNs are emerging as a new element of cortical output, acting in concert with long-range excitatory projections to shape brain function in health and disease.

Is REM sleep a paradoxical state?: Different neurons are activated in the cingulate cortices and the claustrum during wakefulness and paradoxical sleep hypersomnia.

Michel Jouvet proposed in 1959 that REM sleep is a paradoxical state since it was characterized by the association of a cortical activation similar to wakefulness (W) with muscle atonia. Recently, we showed using cFos as a marker of activity that cortical activation during paradoxical sleep (PS) was limited to a few limbic cortical structures in contrast to W during which all cortices were strongly activated. However, we were not able to demonstrate whether the same neurons are activated during PS and W and to rule out that the activation observed was not linked with stress induced by the flowerpot method of PS deprivation. In the present study, we answered to these two questions by combining tdTomato and cFos immunostaining in the innovative TRAP2 transgenic mice exposed one week apart to two periods of W (W-W mice), PS rebound (PSR-PSR) or a period of W followed by a period of PSR (W-PSR mice). Using such method, we showed that different neurons are activated during W and PSR in the anterior cingulate (ACA) and rostral and caudal retrosplenial (rRSP and cRSP) cortices as well as the claustrum (CLA) previously shown to contain a large number of activated neurons after PSR. Further, the distribution of the neurons during PSR in the rRSP and cRSP was limited to the superficial layers while it was widespread across all layers during W. Our results clearly show at the cellular level that PS and W are two completely different states in term of neocortical activation.

Cerebral localization of higher functions: anatomic structures before the identification of their memory function / Localização cerebral de funções superiores: estruturas anatômicas antes da identificação de suas funções de memória

The nature of memory and the search for its localization have been a subject of interest since Antiquity. After millennia of hypothetical concepts the core memory-related structures finally began to be identified through modern scientifically-based methods at the diencephalic, hippocampal, and neocortical levels. However, there was a clear temporal delay between the finding of these anatomic structures ignoring their function, and their identification related to memory function. Thus, the core structures begun to be identified with a pure anatomical view in the late Middle Ages on, while the memory function related to them was discovered much later, in the late Modern Period.

A natureza da memória e a busca de sua localização tem sido objeto de interesse desde a Antiguidade. Após milênios de conceitos hipotéticos as estruturas centrais relacionadas com a memória finalmente começaram a ser identificadas através de métodos modernos com base científica, nos níveis diencefálico, hipocampal e neocortical. Entretanto, houve um claro retardo temporal entre o achado dessas estruturas anatômicas ignorando sua função e sua identificação relacionada à função da memória. Assim, as estruturas centrais começaram a ser identificadas com uma visão puramente anatômica da Idade Média tardia em diante, enquanto a função da memória relacionada com as mesmas foi descoberta muito mais tarde, no Período Moderno tardio.

Cerebral localization of higher functions: Memory-related anatomic structures.

The nature of memory and the search for its localization have been a subject of interest since Antiquity. After millennia of theoretical concepts, shifting from the heart to the brain, then from the ventricles to solid parts, the core memory-related structures finally began to be identified through modern scientifically-based methods at the diencephalic and cortical (hippocampal and neocortical) levels, mostly in the late Modern period, culminating in the current state of knowledge on the subject.

A natureza da memória e a busca de sua localização tem sido objeto de interesse desde a Antiguidade. Após milênios de conceitos teóricos, mudando do coração para o cérebro e daí dos ventrículos para as partes sólidas, as estruturas centrais relacionadas com a memória finalmente começaram a ser identificadas através de métodos modernos com base científica, nos níveis diencefálico e cortical (hipocampal e neocortical), principalmente no período Moderno tardio, aproximando-se do estado atual do conhecimento sobre o tema.

Cerebral localization of higher functions: Memory-related anatomic structures / Localização cerebral de funções superiores: estruturas anatômicas relacionadas com a memória. achados iniciais

ABSTRACT The nature of memory and the search for its localization have been a subject of interest since Antiquity. After millennia of theoretical concepts, shifting from the heart to the brain, then from the ventricles to solid parts, the core memory-related structures finally began to be identified through modern scientifically-based methods at the diencephalic and cortical (hippocampal and neocortical) levels, mostly in the late Modern period, culminating in the current state of knowledge on the subject.

RESUMO A natureza da memória e a busca de sua localização tem sido objeto de interesse desde a Antiguidade. Após milênios de conceitos teóricos, mudando do coração para o cérebro e daí dos ventrículos para as partes sólidas, as estruturas centrais relacionadas com a memória finalmente começaram a ser identificadas através de métodos modernos com base científica, nos níveis diencefálico e cortical (hipocampal e neocortical), principalmente no período Moderno tardio, aproximando-se do estado atual do conhecimento sobre o tema.

Cannabidiol Acts at 5-HT1A Receptors in the Human Brain: Relevance for Treating Temporal Lobe Epilepsy.

Experimental evidence indicates that cannabidiol (CBD) induces anxiolytic and antiepileptic effects through the activation of 5-HT1A receptors. These receptors are coupled to Gi/o proteins and induce inhibitory effects. At present, the interaction of CBD with 5-HT1A receptors in the human brain is unknown. The aim of this study focused on evaluating the interaction between CBD and 5-HT1A receptors in cell membranes obtained from the hippocampus and temporal neocortex of autopsies and patients with drug-resistant mesial temporal lobe epilepsy (DR-MTLE). Cell membranes were isolated from the hippocampus and temporal neocortex of a group of patients with DR-MTLE who were submitted to epilepsy surgery (n = 11) and from a group of autopsies (n = 11). The [3H]-8-OH-DPAT binding assay was used to determine the pharmacological interaction of CBD with 5-HT1A receptors. The [35S]-GTPγS assay was used to investigate the CBD-induced activation of Gi/o proteins through its action on 5-HT1A receptors.The CBD affinity (pK i) for 5-HT1A receptors was similar for autopsies and patients with DR-MTLE (hippocampus: 4.29 and 4.47, respectively; temporal neocortex: 4.67 and 4.74, respectively). Concerning the [35S]-GTPγS assay, no statistically significant changes were observed for both hippocampal and neocortical tissue (p > 0.05) at low CBD concentrations (1 pM to 10 µM). In contrast, at high concentrations (100 µM), CBD reduced the constitutive activity of Gi/o proteins of autopsies and DR-MTLE patients (hippocampus: 39.2% and 39.6%, respectively; temporal neocortex: 35.2% and 24.4%, respectively). These changes were partially reversed in the presence of WAY-100635, an antagonist of 5-HT1A receptors, in the autopsy group (hippocampus, 59.8%, p < 0.0001; temporal neocortex, 71.5%, p < 0.0001) and the group of patients with DR-MTLE (hippocampus, 53.7%, p < 0.0001; temporal neocortex, 68.5%, p < 0.001). Our results show that CBD interacts with human 5-HT1A receptors of the hippocampus and temporal neocortex. At low concentrations, the effect of CBD upon Gi/o protein activation is limited. However, at high concentrations, CBD acts as an inverse agonist of 5-HT1A receptors. This effect could modify neuronal excitation and epileptic seizures in patients with DR-MTLE.

Differential expression of miR-34a, 451, 1260, 1275 and 1298 in the neocortex of patients with mesial temporal lobe epilepsy.

Mesial temporal lobe epilepsy (mTLE) is the most common epilepsy syndrome which will eventually become pharmacologically intractable partial-onset seizures. Regulation of gene expression is an important process in the development of this pathology where microRNAs (miRs) are involved. The role of miRs has been widely studied in the hippocampus of rodents and patients. However, little is known about its differential expression in other brain regions such as the neocortex. The temporal neocortex plays a major role in the generation and propagation of seizures and in synaptic disruption, impairing the excitatory and inhibitory balance. Therefore, we assessed the expression of miR-146a, 34a, 1260, 1275, 1298, 451, 132 and 142-3p in the neocortex of 12 patients with mTLE and compared them with miRs expression found in 10 control samples. We noted a significant decrease in the expression of miR-34a and 1298 in patients with mTLE and a -1.49 to -7.0 fold change respectively compared with controls. Conversely, we observed a significant increase in the expression of miR-451, 1260 and 1275 in patients with a 25.67, 4.09 and a 7.07 fold change respectively compared to controls. Using Pearson correlation, we explored the association between the clinical features of mTLE patients and controls with miRs expression. In the control group we found a significant correlation only with age and miR-146a expression (r = 0.733). The analysis of mTLE patients showed a negative correlation between expression of miR-1260 (r = -0.666) and miR-1298 (r = -0.651) and age. Furthermore, we found a positive correlation between miR-146a expression with seizure frequency (r = 0.803) and a positive correlation between miR-146a and 451 expression with number of antiepileptic drugs used for presurgical treatment (r = 0.715 and 0.611 respectively), thus suggesting a positive correlation with disease severity. These miRs are associated with biological processes such as apoptosis, drug resistance, inflammation, inhibitory and excitatory synaptic transmission, axonal guidance and signaling of neurotrophins. Therefore, deepening our understanding of the targets involved in these miRs will help to elucidate the role of the neocortex in epilepsy.

Morphological evolution of the vertebrate forebrain: From mechanical to cellular processes.

Although the cerebral hemispheres are among the defining characters of vertebrates, each vertebrate class is characterized by a different anatomical organization of this structure, which has become highly problematic for comparative neurobiology. In this article, we discuss some mechanisms involved in the generation of this morphological divergence, based on simple spatial constraints for neurogenesis and mechanical forces generated by increasing neuronal numbers during development, and the different cellular strategies used by each group to overcome these limitations. We expect this view to contribute to unify the diverging vertebrate brain morphologies into general, simple mechanisms that help to establish homologies across groups.

Temporal Flexibility of Systems Consolidation and the Synaptic Occupancy/Reset Theory (SORT): Cues About the Nature of the Engram.

The ability to adapt to new situations involves behavioral changes expressed either from an innate repertoire, or by acquiring experience through memory consolidation mechanisms, by far a much richer and flexible source of adaptation. Memory formation consists of two interrelated processes that take place at different spatial and temporal scales, Synaptic Consolidation, local plastic changes in the recruited neurons, and Systems Consolidation, a process of gradual reorganization of the explicit/declarative memory trace between hippocampus and the neocortex. In this review, we summarize some converging experimental results from our lab that support a normal temporal framework of memory systems consolidation as measured both from the anatomical and the psychological points of view, and propose a hypothetical model that explains these findings while predicting other phenomena. Then, the same experimental design was repeated interposing additional tasks between the training and the remote test to verify for any interference: we found that (a) when the animals were subject to a succession of new learnings, systems consolidation was accelerated, with the disengagement of the hippocampus taking place before the natural time point of this functional switch, but (b) when a few reactivation sessions reexposed the animal to the training context without the shock, systems consolidation was delayed, with the hippocampus prolonging its involvement in retrieval. We hypothesize that new learning recruits from a fixed number of plastic synapses in the CA1 area to store the engram index, while reconsolidation lead to a different outcome, in which additional synapses are made available. The first situation implies the need of a reset mechanism in order to free synapses needed for further learning, and explains the acceleration observed under intense learning activity, while the delay might be explained by a different process, able to generate extra free synapses: depending on the cognitive demands, it deals either with a fixed or a variable pool of available synapses. The Synaptic Occupancy/Reset Theory (SORT) emerged as an explanation for the temporal flexibility of systems consolidation, to encompass the two different dynamics of explicit memories, as well as to bridge both synaptic and systems consolidation in one single mechanism.

Early postnatal environmental enrichment restores neurochemical and functional plasticities of the cerebral cortex and improves learning performance in hidden-prenatally-malnourished young-adult rats.

Moderate reduction of dietary protein (from 25% to 8% casein) in pregnant rats, calorically compensated by carbohydrates, gives rise to 'hidden prenatal malnutrition' (HPM) in the offspring since it does not alter body and brain weights of pups at birth. However, this dietary treatment leads to decreased ß-adrenoceptor signaling and brain derived neurotrophic factor (BDNF) levels in the pup' brain, altogether with defective cortical long-term potentiation (LTP) and lowered visuospatial memory performance. Since early postnatal environmental enrichment (EE) has been shown to exert plastic effects on the developing brain and neuroprotection both on cognition and on structural properties of the neocortex, in the present study we addressed the question of whether early postnatal EE during the lactation period could exert compensatory changes in the expression of ®-adrenergic receptors and BDNF in the neocortex of HPM rats, and if these effects are associated with an improvement or even a restore of both neocortical LTP in vivo and cognitive performance induced by HPM. The results obtained show that EE restored ß-adrenoceptor density, BDNF expression and the ability to support LTP at prefrontal and occipital cortices of HPM rats. Besides, EE improved learning performance in visuospatial and operant conditioning tasks. The latter support the notion that adequate maternal protein nutrition during pregnancy is required for proper brain development and function. Further, the results highlight the role of environmental enrichment during early postnatal life in increasing later brain plasticity and exerting neuroprotection against brain deficits induced by prenatal malnutrition.

Increased protein expression of VEGF-A, VEGF-B, VEGF-C and their receptors in the temporal neocortex of pharmacoresistant temporal lobe epilepsy patients.

The vascular endothelial growth factor (VEGF) system has been shown to play a crucial role in several neuropathological processes. Temporal lobe epilepsy (TLE) is the most common focal epilepsy type in adult humans. We assessed the protein expression levels of VEGF-A, VEGF-B, and VEGF-C, their specific receptors VEGFR-2 and -3, their accessory receptors neuropilins 1 and 2, and PI3 and Akt kinases, in temporal neocortex from pharmacoresistant TLE (PR-TLE) patients and control subjects by western blotting. All proteins were found to be significantly overexpressed in samples of PR-TLE patients, indicating that the VEGF system contributes to PR-TLE pathogenesis and should be further studied.

Apuntes sobre la evolución histórica de la obra de Pedro Ortiz Cabanillas y su teoría sociobiológica informacional / Notes on the historical evolution of the work of Pedro Ortiz Cabanillas and his sociobiological informational theory

RESUMEN La Teoría Sociobiológica Informacional propone una definición radicalmente distinta de los sistemas vivos, y con lo mismo es la única teoría neurológica existente que evade el problema mente-cerebro y que explica la naturaleza de la conciencia humana. Fue desarrollada por Pedro Ortiz Cabanillas entre 1984 y 2011. En este documento vamos a realizar un recuento de todas sus obras más importantes. Incluimos, adicionalmente, material inédito de los años 1998, 1999, 2006, y 2009.

ABSTRACT The Informational Sociobiological Theory proposes a radically-different definition of living systems and, therefore, is the only existing neurological theory that evades the mind-brain problem and explains the nature of human consciousness. It was developed by Pedro Ortiz Cabanillas between 1984 and 2011. In this document we are presenting a listing of his main works. We include, additionally, unpublished material of the years 1998, 1999, 2006, and 2009.

Regiones del encéfalo vinculadas a la interpretación del dolor / Regions of the brain involved with the interpretation of the pain

Introducción: Entre el lugar del daño tisular y la percepción del dolor, ocurre una serie de eventos electroquímicos que se conocen como nocicepción y comprenden cuatro procesos neurofisiológicos conocidos como: transducción, transmisión, modulación y percepción. Objetivo: Aportar información actualizada sobre las regiones del encéfalo vinculadas a la interpretación del dolor. Material y Método: Se realizó una revisión bibliográfica, con vistas a esclarecer la interpretación de la señal nociceptiva. Se consultaron treinta y cinco artículos científicos, se determinó escoger un total de veintinueve por su relación directa con el propósito de la búsqueda, veintitrés de los cuales corresponden a los últimos 5 años publicados en revistas internacionales y nacionales. Desarrollo: Los axones nociceptivos se clasifican como A δ; y C, participan en la conducción de los potenciales de acción de la periferia al sistema nervioso central. La transmisión de la señal en forma de potenciales de acción se descodifica en áreas relacionadas con aspectos cognoscitivos, afectivo, emocional y conductual del dolor. Este disímil conjunto de estructuras se reconoce en la actualidad como matriz encefálica del dolor. Conclusiones: La matriz del dolor, corresponde a áreas encefálicas como las cortezas somestésicas SI y SII, implicadas en el aspecto discriminativo del dolor. La corteza cingulada anterior y la corteza insular están asociadas al componente afectivo emocional del dolor(AU)

Introduction: A series of electrochemical events called nociception occur between the tissue damage and the perception of pain. They include four neurophysiological processes known as: transduction, transmission, perception, and modulation. Objective: To provide up-to-date information about the regions of the brain involved with the interpretation of pain. Material and Method: A bibliographic review was carried out with the aim of clarifying the interpretation of the nociceptive signal. Thirty-five scientific articles were consulted, and a total of twenty-nine were chosen due to their direct relationship with the aim of the search, twenty-three of which correspond to the last five years of publication in national and international journals. Development: Nociceptive axons are classified as Aδ; and C, and participate in the conduction of action potential of the peripheral nervous system (PNS). The transmission of the signal in the form of action potential is decoded in areas related to cognoscitive, affective, and emotional aspects, and the behavioral area of pain. This dissimilar group of structures is recognized at present as the brain matrix of pain. Conclusions: The pain matrix corresponds to brain areas such as SI and SII somatosensory cortices, implied in the discriminative aspect of pain. Both the anterior cingulate cortex (ACC) and the anterior insular cortex (AIC) are associated with the emotional and affective component of pain(AU)

Brain development is impaired in c-fos -/- mice.

c-Fos is a proto-oncogene involved in diverse cellular functions. Its deregulation has been associated to abnormal development and oncogenic progression. c-fos-/- mice are viable but present a reduction in their body weight and brain size. We examined the importance of c-Fos during neocortex development at 13.5, 14.5 and 16.5 days of gestation. At E14.5, neocortex thickness, apoptosis, mitosis and expression of markers along the different stages of Neural Stem Progenitor Cells (NSPCs) differentiation in c-fos-/- and wild-type mice were analyzed. A ~15% reduction in the neocortex thickness of c-fos-/- embryos was observed which correlates with a decrease in the number of differentiated cells and an increase in apoptosis at the ventricular zone. No difference in mitosis rate was observed, although the mitotic angle was predominantly vertical in c-fos-/- embryos, suggesting a reduced trend of NSPCs to differentiate. At E13.5, changes in differentiation markers start to be apparent and are still clearly observed at E16.5. A tendency of more AP-1/DNA complexes present in nuclear extracts of cerebral cortex from c-fos-/- embryos with no differences in the lipid synthesis activity was found. These results suggest that c-Fos is involved in the normal development of NSPCs by means of its AP-1 activity.

GABAergic alterations in neocortex of patients with pharmacoresistant temporal lobe epilepsy can explain the comorbidity of anxiety and depression: the potential impact of clinical factors.

Temporal lobe epilepsy (TLE) is a chronic neurodegenerative disease with a high prevalence of psychiatric disorders. Temporal neocortex contributes to either seizure propagation or generation in TLE, a situation that has been associated with alterations of the γ-amino-butyric acid (GABA) system. On the other hand, an impaired neurotransmission mediated by GABA in temporal neocortex has also been involved with the pathophysiology of psychiatric disorders. In spite of these situations, the role of the necortical GABA system in the comorbidity of TLE and mood disorders has not been investigated. The present study was designed to identify alterations in the GABA system such as binding to GABAA and GABAB receptors and benzodiazepine site, the tissue content of GABA and the expression of the mRNA encoding the α1-6, ß1-3, and γ GABAA subunits, in the temporal neocortex of surgically treated patients with TLE with and without anxiety, and/or depression. Neocortex of patients with TLE and comorbid anxiety and/or depression showed increased expression of the mRNA encoding the γ2-subunit, reduced GABAB-induced G-protein activation in spite of elevated GABAB binding, and lower tissue content of GABA when compared to autopsy controls. Some of these changes significantly correlated with seizure frequency and duration of epilepsy. The results obtained suggest a dysfunction of the GABAergic neurotransmission in temporal neocortex of patients with TLE and comorbid anxiety and/or depression that could be also influenced by clinical factors such as seizure frequency and duration of illness.

Modelo computacional preliminar de la formación de la superficie cerebral / Preliminary computation form of the cerebral surface development

La corteza cerebral es una lámina gris, formada por cuerpos de neuronas, que cubre los hemisferios cerebrales y cuyo grosor varía de 1,25 mm en el lóbulo occipital a 4 mm en el lóbulo anterior. Debido a los numerosos pliegues que presenta, la superficie cerebral es unas 30 veces mayor que la superficie del cráneo. Estos pliegues forman las circunvoluciones cerebrales, surcos y fisuras y delimitan áreas con funciones determinadas, divididas en cinco lóbulos. La formación de las circunvoluciones puede variar entre individuos y constituyen una característica importante de la formación del cerebro. Estos patrones se pueden representar, de forma matemática, como patrones de Turing. En este artículo se desarrolla un modelo fenomenológico que describe la formación de los patrones de las circunvoluciones que ocurren en la corteza cerebral mediante ecuaciones de reacción difusión con parámetros en el espacio de Turing. Para estudiar la formación de patrones se resuelven varios ejemplos numéricos sobre geometrías simplificadas de un cerebro. Para la solución numérica se utilizó el método de los elementos finitos en conjunto con el método de Newton-Raphson. Los ejemplos numéricos muestran que el modelo puede representar la formación de los pliegues de la corteza cerebral y reproducir patologías de la formación de las circunvoluciones, tales como polimicrogiria y lisencefalia.

Cerebral cortex is a gray layer including neuron bodies covering the cerebral hemispheres and whose thickness fluctuates from 1.25 mm in the occipital lobule to 4 mm in the anterior lobule. Due to the many folds present, la cerebral surface is a thirty times greater than the cranial surface. These folds create the cerebral convolutions, grooves and fissures defining areas with determined functions, divided into five lobules. La convolutions formation may to vary among subjects and are an important characteristic of brain formation. These patterns may be represented in a mathematical way like Turing patterns. The aim of present paper was to design a phenomenological model describing the formation of convolutions patterns occurring in the cerebral cortex by means of diffusion reaction equations with parameters in the Turing space. To study la formation of patterns it is necessary to solve some numerical examples on simplified geometries of a brain. For numerical solution authors used the finite elements method together with the Newton-Raphson method. The numerical examples demonstrate that this model may to represent the folds formation in the cerebral cortex and to reproduce pathologies of the convolutions formation, such as the polymicrogyria and lissencephalous.