RESUMEN
The left temporal lobe is an integral part of the language system and its cortical structure and function associate with general intelligence. However, whether cortical laminar architecture and cellular properties of this brain area relate to verbal intelligence is unknown. Here, we addressed this using histological analysis and cellular recordings of neurosurgically resected temporal cortex in combination with presurgical IQ scores. We find that subjects with higher general and verbal IQ scores have thicker left (but not right) temporal cortex (Brodmann area 21, BA21). The increased thickness is due to the selective increase in layers 2 and 3 thickness, accompanied by lower neuron densities, and larger dendrites and cell body size of pyramidal neurons in these layers. Furthermore, these neurons sustain faster action potential kinetics, which improves information processing. Our results indicate that verbal mental ability associates with selective adaptations of supragranular layers and their cellular micro-architecture and function in left, but not right temporal cortex.
Asunto(s)
Células Piramidales , Lóbulo Temporal , Potenciales de Acción , Humanos , Inteligencia/fisiología , Neuronas/fisiología , Células Piramidales/fisiología , Lóbulo Temporal/patologíaRESUMEN
Electrical stimulation of certain hypothalamic regions in cats and rodents can elicit attack behaviour, but the exact location of relevant cells within these regions, their requirement for naturally occurring aggression and their relationship to mating circuits have not been clear. Genetic methods for neural circuit manipulation in mice provide a potentially powerful approach to this problem, but brain-stimulation-evoked aggression has never been demonstrated in this species. Here we show that optogenetic, but not electrical, stimulation of neurons in the ventromedial hypothalamus, ventrolateral subdivision (VMHvl) causes male mice to attack both females and inanimate objects, as well as males. Pharmacogenetic silencing of VMHvl reversibly inhibits inter-male aggression. Immediate early gene analysis and single unit recordings from VMHvl during social interactions reveal overlapping but distinct neuronal subpopulations involved in fighting and mating. Neurons activated during attack are inhibited during mating, suggesting a potential neural substrate for competition between these opponent social behaviours.
Asunto(s)
Agresión/fisiología , Núcleo Hipotalámico Ventromedial/citología , Núcleo Hipotalámico Ventromedial/fisiología , Animales , Estimulación Eléctrica , Electrofisiología , Femenino , Regulación de la Expresión Génica , Genes fos/genética , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Inhibición Neural/genética , Inhibición Neural/fisiología , Vías Nerviosas/fisiología , Neuronas/fisiología , Conducta Sexual Animal/fisiología , Núcleo Hipotalámico Ventromedial/anatomía & histología , Núcleo Hipotalámico Ventromedial/metabolismoRESUMEN
The hippocampus consists of distinct anatomic regions that have been demonstrated to have different biological functions. To explore the molecular differences between hippocampal subregions, we performed transcriptional profiling analysis by using DNA microarray technology. The cRNA derived from the CA1, CA3, and dentate gyrus regions of the hippocampus and from spinal cord was hybridized to Affymetrix high-density oligo arrays. This systematic approach revealed sets of genes that were expressed specifically in subregions of the hippocampus corresponding to predefined cytoarchitectural boundaries, which could be confirmed by in situ hybridization and Real Time quantitative polymerase chain reaction. The relative enrichment and absence of genes in the hippocampal subregions support the conclusion that there is a molecular basis for the previously defined anatomic subregions of the hippocampus and also reveal genes that could be important in defining the unique functions of the hippocampal subfields.
Asunto(s)
Perfilación de la Expresión Génica , Hipocampo/anatomía & histología , Transcripción Genética , Animales , Sistemas de Computación , Giro Dentado/fisiología , Expresión Génica , Hipocampo/fisiología , Hibridación in Situ , Masculino , Ratones , Análisis de Secuencia por Matrices de Oligonucleótidos , Reacción en Cadena de la Polimerasa , ARN Complementario/genética , Médula Espinal/fisiologíaRESUMEN
In situ hybridization of mouse embryo whole mounts and sagittal sections revealed a tissue- and stage-specific expression pattern of the transcriptionally regulated serum and glucocorticoid-inducible protein kinase (sgk) during embryogenesis. Sgk expression is first observed at embryonic day 8.5 (E8.5) in the decidua and yolk sac, and then during developmental stages E9.5 through E12.5 this kinase is highly localized in the heart chamber, otic vesicle, blood vessels surrounding the somites, and lung buds. At the later stages of mouse embryogenesis, E13.5 through E16.5, sgk expression becomes highly concentrated in brain (choroid plexus), distal epithelium and the terminal bronchi/bronchioles, adrenal gland, liver, thymus and intestines, remains high in heart tissue, and is expressed at a low level in the other embryonic tissues.
Asunto(s)
Embrión de Mamíferos/metabolismo , Proteínas Nucleares , Proteínas Serina-Treonina Quinasas/biosíntesis , Animales , Encéfalo/embriología , ADN Complementario/metabolismo , Epitelio/embriología , Corazón/embriología , Proteínas Inmediatas-Precoces , Hibridación in Situ , Pulmón/embriología , Pulmón/metabolismo , Ratones , Factores de Tiempo , Distribución Tisular , Transcripción GenéticaRESUMEN
Recent studies have proposed roles for neurotrophins in the formation and plasticity of ocular dominance columns as well as in the regulation of dendritic arborization in visual cortex of higher mammals. To assess potential roles for neurotrophins in these processes, we have examined the developmental expression of BDNF and NT-3 mRNA in the cat's visual system using in situ hybridization. BDNF and NT-3 mRNAs are dynamically regulated in many CNS structures during embryonic and postnatal development, and both mRNAs undergo striking developmental changes in laminar specificity and levels of expression within primary visual cortex during the critical period for ocular dominance column formation. Within visual cortex, BDNF mRNA is found in neurons in deep cortical layers (5 and 6) prior to eye opening, and in both deep and superficial layers (2 and 3) shortly afterwards. Within layer 4, the target of thalamocortical axons, BDNF mRNA is low initially and rises to high levels by the end of the critical period for ocular dominance column formation. NT-3 mRNA is first detectable in small stellate neurons at the base of layer 4 (4c) after eye opening, and levels decrease near the end of the critical period. BDNF and NT-3 mRNAs can be detected in the lateral geniculate nucleus at birth, and levels peak during the critical period. In both structures, BDNF mRNA expression is maintained into adulthood, while NT-3 is undetectable in the adult. The presence and dynamic regulation of these neurotrophins in visual structures is consistent with suggested roles for both of these neurotrophins in axonal and dendritic remodeling known to accompany the formation of ocular dominance columns.
Asunto(s)
Factor Neurotrófico Derivado del Encéfalo/genética , Neurotrofina 3/genética , Vías Visuales/embriología , Vías Visuales/crecimiento & desarrollo , Factores de Edad , Animales , Animales Recién Nacidos , Gatos , Embrión de Mamíferos , Cuerpos Geniculados/citología , Cuerpos Geniculados/embriología , Cuerpos Geniculados/crecimiento & desarrollo , Neuronas/citología , Neuronas/metabolismo , ARN Mensajero/análisis , ARN Mensajero/metabolismo , Ribonucleasas/análisis , Corteza Visual/citología , Corteza Visual/embriología , Corteza Visual/crecimiento & desarrollo , Vías Visuales/citologíaRESUMEN
The neurotrophin brain-derived neurotrophic factor (BDNF) has emerged as a candidate retrograde signaling molecule for geniculocortical axons during the formation of ocular dominance columns. Here we examined whether neuronal activity can regulate BDNF mRNA in eye-specific circuits in the developing cat visual system. Dark-rearing throughout the critical period for ocular dominance column formation decreases levels of BDNF mRNA within primary visual cortex, whereas short-term (2 d) binocular blockade of retinal activity with tetrodotoxin (TTX) downregulates BDNF mRNA within the lateral geniculate nucleus (LGN) and visual cortical areas. Brief (6 hr to 2 d) monocular TTX blockade during the critical period and also in adulthood causes downregulation in appropriate eye-specific laminae in the LGN and ocular dominance columns within primary visual cortex. Monocular TTX blockade at postnatal day 23 also downregulates BDNF mRNA in a periodic fashion, consistent with recent observations that ocular dominance columns can be detected at these early ages by physiological methods. In contrast, 10 d monocular TTX during the critical period does not cause a lasting decrease in BDNF mRNA expression in columns pertaining to the treated eye, consistent with the nearly complete shift in physiological response properties of cortical neurons in favor of the unmanipulated eye known to result from long-term monocular deprivation. These observations demonstrate that BDNF mRNA levels can provide an accurate "molecular readout" of the activity levels of cortical neurons and are consistent with a highly local action of BDNF in strengthening and maintaining active synapses during ocular dominance column formation.
Asunto(s)
Factor Neurotrófico Derivado del Encéfalo/genética , Dominancia Cerebral/genética , Regulación del Desarrollo de la Expresión Génica , Transcripción Genética , Corteza Visual/fisiología , Vías Visuales/fisiología , Envejecimiento , Animales , Gatos , Oscuridad , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Cuerpos Geniculados/metabolismo , Cuerpos Geniculados/fisiología , ARN Mensajero/genética , Colículos Superiores/metabolismo , Colículos Superiores/fisiología , Tetrodotoxina/farmacología , Visión Binocular , Visión Monocular , Corteza Visual/crecimiento & desarrollo , Corteza Visual/metabolismo , Vías Visuales/crecimiento & desarrollo , Vías Visuales/metabolismoRESUMEN
Ocular dominance column formation in visual cortex depends on both the presence of subplate neurons and the endogenous expression of neurotrophins. Here we show that deletion of subplate neurons, which supply glutamatergic inputs to visual cortex, leads to a paradoxical increase in brain-derived neurotrophic factor mRNA in the same region of visual cortex in which ocular dominance columns are absent. Subplate neuron ablation also increases glutamic acid decarboxylase-67 levels, indicating an alteration in cortical inhibition. These observations imply a role for this special class of neurons in modulating activity-dependent competition by regulating levels of neurotrophins and excitability within a developing cortical circuit.