RESUMEN
Exploring the nature of human intelligence and behavior is a longstanding pursuit in cognitive neuroscience, driven by the accumulation of knowledge, information, and data across various studies. However, achieving a unified and transparent interpretation of findings presents formidable challenges. In response, an explainable brain computing framework is proposed that employs the never-ending learning paradigm, integrating evidence combination and fusion computing within a Knowledge-Information-Data (KID) architecture. The framework supports continuous brain cognition investigation, utilizing joint knowledge-driven forward inference and data-driven reverse inference, bolstered by the pre-trained language modeling techniques and the human-in-the-loop mechanisms. In particular, it incorporates internal evidence learning through multi-task functional neuroimaging analyses and external evidence learning via topic modeling of published neuroimaging studies, all of which involve human interactions at different stages. Based on two case studies, the intricate uncertainty surrounding brain localization in human reasoning is revealed. The present study also highlights the potential of systematization to advance explainable brain computing, offering a finer-grained understanding of brain activity patterns related to human intelligence.
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Encéfalo , Humanos , Encéfalo/fisiología , Encéfalo/diagnóstico por imagen , Cognición/fisiología , Aprendizaje/fisiología , Inteligencia/fisiologíaRESUMEN
In this study, we developed an evaluation method using image analysis for reaching tasks. Using this method, we studied forearm function during the reaching task in rats that received a unilateral injection of 6-OHDA into the striatum. The success ratio of the reaching task reduced to 40.5% seven days after the injection. In addition, significant changes were observed in the pronation angle of the forearm, posture control, and targeting (i.e., the distance between all fingertips and the center of the target pellet). Thus, unilateral injection of 6-OHDA reduces dopaminergic function in the brain and causes deterioration of forearm function and posture control in the reaching task.
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Cuerpo Estriado , Dopamina , Animales , Dopamina/farmacología , Humanos , Oxidopamina/farmacología , RatasRESUMEN
The rat reaching task is one of the best paradigms from behavioral study of upper limb movements. Rats are trained to reach and grab a pellet by extending their hand through a vertical slit. A few conventional imaging systems specific for the rat reaching task are commercially available with a high installation cost. Based on image analysis of video recordings obtained during the reaching task, we, herewith, developed a new, low-cost laboratory system that can be used for the quantitative analysis of ten basic forearm movements, in contrast to subjective assessments used in previous studies. We quantified images of the pronated and supinated palm and the accuracy and speed of reaching the target. Applying this newly developed method, we compared the forearm movements during the reaching task before and after a massive anatomical lesion of the sensorimotor cortex performed by tissue aspiration. We also wanted to investigate the recovery of upper limb function possibly induced by repeating the task for a relatively short term of a few weeks. In the experiment, 7 injured groups and 3 control groups were used. We found characteristic abnormalities of the forearm movements and a significant recovery in the success rate of grasping the target pellet. The present results demonstrate that our method is straightforward for the quantitative evaluation of forearm movements during the reaching task primarily controlled by the sensorimotor cortex.
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Lesiones Traumáticas del Encéfalo/fisiopatología , Miembro Anterior/fisiopatología , Actividad Motora/fisiología , Corteza Motora/lesiones , Neurociencias , Desempeño Psicomotor/fisiología , Recuperación de la Función/fisiología , Animales , Conducta Animal/fisiología , Modelos Animales de Enfermedad , Femenino , Masculino , Neurociencias/instrumentación , Neurociencias/métodos , Ratas , Ratas Long-Evans , Grabación en VideoRESUMEN
Ocular dominance plasticity (ODP) is a type of cortical plasticity operating in visual cortex of mammals that are endowed with binocular vision based on the competition-driven disparity. Earlier, a molecular mechanism was proposed that catecholamines play an important role in the maintenance of ODP in kittens. Having survived the initial test, the hypothesis was further advanced to identify noradrenaline (NA) as a key factor that regulates ODP in the immature cortex. Later, the ODP-promoting effect of NA is extended to the adult with age-related limitations. Following the enhanced NA availability, the chain events downstream lead to the ß-adrenoreceptor-induced cAMP accumulation, which in turn activates the protein kinase A. Eventually, the protein kinase translocates to the cell nucleus to activate cAMP responsive element binding protein (CREB). CREB is a cellular transcription factor that controls the transcription of various genes, underpinning neuronal plasticity and long-term memory. In the advent of molecular genetics in that various types of new tools have become available with relative ease, ODP research has lightly adopted in the rodent model the original concepts and methodologies. Here, after briefly tracing the strategic maturation of our quest, the review moves to the later development of the field, with the emphasis placed around the following issues: (a) Are we testing ODP per se? (b) What does monocular deprivation deprive of the immature cortex? (c) The critical importance of binocular competition, (d) What is the adult plasticity? (e) Excitation-Inhibition balance in local circuits, and (f) Species differences in the animal models.
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Predominio Ocular/fisiología , Plasticidad Neuronal/fisiología , Corteza Visual/citología , Corteza Visual/metabolismo , Animales , Proteína de Unión a CREB/metabolismo , AMP Cíclico/metabolismo , Humanos , Norepinefrina/metabolismo , Estimulación Luminosa/métodos , Privación Sensorial/fisiologíaRESUMEN
Developmental changes in the expression and localization of drebrin has been mainly analyzed in chick embryo and young rat by various anti-drebrin polyclonal and monoclonal antibodies. Immunoblot analysis demonstrated that the adult drebrin isoform (drebrin A) is restricted to neural tissues, while the embryonic drebrin isoforms (drebrin E1 and E2 in chicken and drebrin E in mammals) are found in a wide variety of tissues. In the developing brain, drebrin E (including chicken drebrin E2) is expressed in newly generated neurons. During neuronal migration, drebrin E is distributed ubiquitously within the neurons. Once drebrin A is expressed in the developing neuron, drebrin E is no longer present within the cell soma and accumulates in the growth cone of growing processes, resulting in the cessation of neuronal migration. The limited subcellular localization of drebrin A, which is possibly regulated by a drebrin A-specific mechanism, is likely to affect the localization of drebrin E. In the adult brain, drebrin is mainly localized in dendritic spines, but in some nuclei, drebrin can be detected in neuronal somata as well as dendritic spines. The fact that the developmental changes in drebrin expression highly correlate in time with the sensitive period of visual cortical plasticity in kittens suggests that synaptic plasticity depends on drebrin.
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Plasticidad Neuronal , Neuronas/metabolismo , Neuropéptidos/aislamiento & purificación , Corteza Visual/diagnóstico por imagen , Animales , Gatos , Embrión de Pollo , Pollos/metabolismo , Espinas Dendríticas/química , Espinas Dendríticas/metabolismo , Espinas Dendríticas/ultraestructura , Microscopía , Neuronas/química , Neuronas/ultraestructura , Neuropéptidos/biosíntesis , Neuropéptidos/metabolismo , Ratas , Corteza Visual/química , Corteza Visual/metabolismoRESUMEN
The neuronal mechanisms underlying arithmetic calculations are not well understood but the differences between mental addition and subtraction could be particularly revealing. Using fMRI and dynamic causal modeling (DCM), this study aimed to identify the distinct neuronal architectures engaged by the cognitive processes of simple addition and subtraction. Our results revealed significantly greater activation during subtraction in regions along the dorsal pathway, including the left inferior frontal gyrus (IFG), middle portion of dorsolateral prefrontal cortex (mDLPFC), and supplementary motor area (SMA), compared with addition. Subsequent analysis of the underlying changes in connectivity - with DCM - revealed a common circuit processing basic (numeric) attributes and the retrieval of arithmetic facts. However, DCM showed that addition was more likely to engage (numeric) retrieval-based circuits in the left hemisphere, while subtraction tended to draw on (magnitude) processing in bilateral parietal cortex, especially the right intraparietal sulcus (IPS). Our findings endorse previous hypotheses about the differences in strategic implementation, dominant hemisphere, and the neuronal circuits underlying addition and subtraction. Moreover, for simple arithmetic, our connectivity results suggest that subtraction calls on more complex processing than addition: auxiliary phonological, visual, and motor processes, for representing numbers, were engaged by subtraction, relative to addition. Hum Brain Mapp 38:3210-3225, 2017. © 2017 Wiley Periodicals, Inc.
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Mapeo Encefálico , Encéfalo/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Matemática , Modelos Neurológicos , Vías Nerviosas/diagnóstico por imagen , Adulto , Encéfalo/fisiología , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Vías Nerviosas/fisiología , Oxígeno/sangre , Solución de Problemas/fisiología , Tiempo de Reacción/fisiología , Adulto JovenRESUMEN
Altered brain function in patients with major depressive disorder (MDD) has been repeatedly demonstrated by task-based and resting-state studies, respectively. However, less is known concerning whether overlapped abnormalities in functional activities across modalities exist in MDD patients. To find out the answer, we implemented an fMRI experiment and collected both task and resting-state data from 19 MDD patients and 19 matched, healthy, controls. A distraction paradigm involving emotionally valenced pictures was applied to induce affective responses in subjects. As a result, concurrent deficits were found in arousing activation during a positive task in both the reward circuit and salience network (SN) that is composed of the dorsal part of anterior cingulate cortex (dACC) and bilateral anterior insulae (AI) in only the MDD group. Subsequent amplitude of low frequency fluctuations (ALFF) and functional connectivity analyses based on resting-state data exhibited consistent alterations in the bilateral AI of MDD patients, and indicated patients' difficulties in regulating the balance between central executive network (CEN) and default mode network (DMN) due to altered connectivity among the CEN, DMN, and SN. Our findings provide new evidence demonstrating impaired salience processing and resulting alterations in responses to positive stimuli in MDD patients. Furthermore, brain abnormalities synchronized across functional states in MDD patients can be evidenced by a combination of task and resting-state fMRI analyses.
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Mapeo Encefálico , Trastorno Depresivo Mayor/fisiopatología , Adulto , Estudios de Casos y Controles , Trastorno Depresivo Mayor/diagnóstico por imagen , Función Ejecutiva , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Análisis y Desempeño de TareasRESUMEN
Altered sensory experience in early life often leads to remarkable adaptations so that humans and animals can make the best use of the available information in a particular environment. By restricting visual input to a limited range of orientations in young animals, this investigation shows that stimulus selectivity, e.g., the sharpness of tuning of single neurons in the primary visual cortex, is modified to match a particular environment. Specifically, neurons tuned to an experienced orientation in orientation-restricted animals show sharper orientation tuning than neurons in normal animals, whereas the opposite was true for neurons tuned to non-experienced orientations. This sharpened tuning appears to be due to elongated receptive fields. Our results demonstrate that restricted sensory experiences can sculpt the supranormal functions of single neurons tailored for a particular environment. The above findings, in addition to the minimal population response to orientations close to the experienced one, agree with the predictions of a sparse coding hypothesis in which information is represented efficiently by a small number of activated neurons. This suggests that early brain areas adopt an efficient strategy for coding information even when animals are raised in a severely limited visual environment where sensory inputs have an unnatural statistical structure.
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Orientación/fisiología , Corteza Visual/fisiología , Vías Visuales/fisiología , Animales , Gatos , Fenómenos Electrofisiológicos , Dispositivos de Protección de los Ojos , Imagen Óptica , Estimulación LuminosaRESUMEN
We examined lateral geniculate nucleus (LGN) degeneration as an indicator for possible diagnosis of glaucoma in experimental glaucoma monkeys using positron emission tomography (PET). Chronic intraocular pressure (IOP) elevation was induced by laser trabeculoplasty in the left eyes of 5 cynomolgus monkeys. Glial cell activation was detected by PET imaging with [(11)C]PK11195, a PET ligand for peripheral-type benzodiazepine receptor (PBR), before and at 4 weeks after laser treatment (moderate glaucoma stage). At mild, moderate, and advanced experimental glaucoma stages (classified by histological changes based on the extent of axonal loss), brains were stained with cresyl violet, or antibodies against PBR, Iba-1 (a microglial marker), and GFAP (an activated astrocyte marker). In laser-treated eyes, IOP was persistently elevated throughout all observation periods. PET imaging showed increased [(11)C]PK11195 binding potential in the bilateral LGN at 4 weeks after laser treatment; the increase in the ipsilateral LGN was statistically significant (P<0.05, n = 4). Immunostaining showed bilateral activations of microglia and astrocytes in LGN layers receiving input from the laser-treated eye. PBR-positive cells were observed in LGN layers receiving input from laser-treated eye at all experimental glaucoma stages including the mild glaucoma stage and their localization coincided with Iba-1 positive microglia and GFAP-positive astrocytes. These data suggest that glial activation occurs in the LGN at a mild glaucoma stage, and that the LGN degeneration could be detected by a PET imaging with [(11)C]PK11195 during the moderate experimental glaucoma stage after unilateral ocular hypertension. Therefore, activated glial markers such as PBR in the LGN may be useful in noninvasive molecular imaging for diagnosis of glaucoma.
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Modelos Animales de Enfermedad , Cuerpos Geniculados/patología , Glaucoma/diagnóstico por imagen , Glaucoma/patología , Macaca fascicularis , Neuroglía/diagnóstico por imagen , Animales , Cuerpos Geniculados/diagnóstico por imagen , Cuerpos Geniculados/fisiopatología , Cuerpos Geniculados/cirugía , Glaucoma/fisiopatología , Glaucoma/cirugía , Humanos , Presión Intraocular/fisiología , Terapia por Láser , Degeneración Nerviosa/diagnóstico por imagen , Degeneración Nerviosa/patología , Degeneración Nerviosa/fisiopatología , Degeneración Nerviosa/cirugía , Neuroglía/metabolismo , Neuroglía/fisiología , Hipertensión Ocular/diagnóstico por imagen , Hipertensión Ocular/patología , Enfermedades del Nervio Óptico/diagnóstico por imagen , Enfermedades del Nervio Óptico/patología , Enfermedades del Nervio Óptico/fisiopatología , Enfermedades del Nervio Óptico/cirugía , Tomografía de Emisión de Positrones , Resultado del TratamientoRESUMEN
We investigated whether endoplasmic reticulum (ER) stress was involved in the pathophysiological mechanisms underlying neuronal death of the lateral geniculate nucleus (LGN) after intraocular pressure (IOP) elevation. Five cynomolgus monkeys, four with a glaucomatous left eye after laser photocoagulation treatment and one normal monkey, were studied. At 4, 11, 15 and 24 weeks after the laser photocoagulation treatment, the numbers of LGN neurons and atrophy were immunohistochemically evaluated using anti-parvalbumin-antibody, which was used to specifically label relay neurons connecting to the visual cortex. In addition, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells, polyubiquitin, and production of ER stress-related proteins, such as the phosphorylation of eukaryotic initiation factor 2α (p-eIF2α) and C/EBP-homologous protein (CHOP), were also measured using in situ hybridization and immunostaining. Loss of neurons and/or neuronal atrophy in layers 1, 4 and 6 of the LGN on the contralateral side were observed at 4-24 weeks after the laser photocoagulation treatment. Furthermore, the retinal input from the high IOP eye projected to layers 2 (magnocellular layer), 3 and 5 (parvocellular layer) on the ipsilateral side. Neuronal damage was also confirmed in these layers. In the LGN region, TUNEL-positive cells, polyubiquitin, p-eIF2α and CHOP were also detected at 11-24 weeks after the laser photocoagulation treatment. These findings indicate that ER stress may play a pivotal role in neuronal death of the LGN after IOP elevation.
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Muerte Celular/fisiología , Modelos Animales de Enfermedad , Retículo Endoplásmico/metabolismo , Cuerpos Geniculados , Glaucoma/fisiopatología , Neuronas/fisiología , Estrés Fisiológico , Animales , Cuerpos Geniculados/citología , Cuerpos Geniculados/patología , Cuerpos Geniculados/fisiología , Glaucoma/patología , Humanos , Etiquetado Corte-Fin in Situ , Presión Intraocular/fisiología , Macaca fascicularis , Masculino , Neuronas/citología , Nervio Óptico/citología , Nervio Óptico/patología , Nervio Óptico/fisiología , Retina/citología , Retina/patología , Retina/fisiología , Factor de Transcripción CHOP/metabolismoRESUMEN
Physiological and lesion studies have shown that the anterior inferior temporal (IT) cortex (aITC) is involved in the color vision of macaque monkeys. However, some functional imaging studies using awake monkeys contradicted the involvement of aITC in color vision. Thus, in most of the imaging studies, cortical activation has been observed during a fixation task. However, because the neuronal activity of aITC is highly affected by the behavioral task, it is desirable to investigate cortical activity during a color discrimination task to determine the functional role of aITC in the color vision of macaque monkeys. In this study, we investigated the cortical activity of aITC of macaque monkeys during color discrimination by positron emission tomography. Two monkeys were trained in a color discrimination task. Cortical areas involved in color processing were investigated by comparing activities during the color discrimination and lever release tasks. In addition to area V4 and the posterior IT cortex (pITC), we found color-related activities in the anterior IT gyrus. Consistent activation was observed in the region posterior to the anterior medial temporal sulcus (AMTS), although the exact location and the size of activations differed between monkeys and hemispheres. We also found color-related activities in the anterior portion of the superior temporal sulcus (STS), suggesting its involvement in the color vision. The present results revealed that aITC is involved in the color vision of macaque monkeys by a functional imaging technique.
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Corteza Cerebral/fisiología , Visión de Colores/fisiología , Aprendizaje Discriminativo/fisiología , Reconocimiento Visual de Modelos/fisiología , Animales , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/metabolismo , Macaca , Masculino , Estimulación Luminosa , Tomografía de Emisión de Positrones , Técnicas EstereotáxicasRESUMEN
Orientation selectivity of primary visual cortical neurons is an important requisite for shape perception. Although numerous studies have been previously devoted to a question of how orientation selectivity is established and elaborated in early life, how the susceptibility of orientation plasticity to visual experience changes in time remains unclear. In the present study, we showed a postnatal sensitive period profile for the modifiability of orientation selectivity in the visual cortex of kittens reared with head-mounted goggles for stable single-orientation exposure. When goggle rearing (GR) started at P16-P30, 2 weeks of GR induced a marked over-representation of the exposed orientation, and 2 more weeks of GR consolidated the altered orientation maps. GR that started later than P50, in turn, induced the under-representation of the exposed orientation. Orientation plasticity in the most sensitive period was markedly suppressed by cortical infusion of NMDAR antagonist. The present study reveals that the plasticity and consolidation of orientation selectivity in an early life are dynamically regulated in an experience-dependent manner.
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Plasticidad Neuronal/fisiología , Orientación/fisiología , Corteza Visual/crecimiento & desarrollo , Corteza Visual/fisiología , 2-Amino-5-fosfonovalerato/administración & dosificación , Factores de Edad , Animales , Gatos , Plasticidad Neuronal/efectos de los fármacos , Orientación/efectos de los fármacos , Estimulación Luminosa , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Receptores de N-Metil-D-Aspartato/fisiología , Corteza Visual/efectos de los fármacosRESUMEN
Adrenergic agonists have different modulatory effects on excitatory synaptic transmission depending on the receptor subtypes involved. The present study examined the loci of alpha(1)- and beta-adrenoceptor agonists, which have opposite effects on excitatory neural transmission, involved in modulation of glutamatergic transmission in layer V pyramidal cells of rat cerebral cortex. Phenylephrine, an alpha(1)-adrenoceptor agonist, suppressed the amplitude of AMPA receptor-mediated excitatory postsynaptic currents evoked by repetitive electrical stimulation (eEPSCs, 10 pulses at 33 Hz). The coefficient of variation (CV) of the 1st eEPSC amplitude and paired-pulse ratio (PPR), which were sensitive to extracellular Ca(2+) concentration, were not affected by phenylephrine. Phenylephrine suppressed miniature EPSC (mEPSC) amplitude without changing its frequency. In contrast, isoproterenol, a beta-adrenoceptor agonist, strongly increased the amplitude of the 1st eEPSC compared with that of the 2nd to 10th eEPSCs, which resulted in a decrease in PPR. Isoproterenol-induced enhancement of eEPSC amplitude was accompanied by a decrease in CV. Isoproterenol increased the frequency of mEPSCs without significant effect on amplitude. Phenylephrine suppressed inward currents evoked by puff application of glutamate, AMPA, or NMDA, whereas isoproterenol application was not accompanied by significant changes in these inward currents. These findings suggest that phenylephrine decreases eEPSCs through postsynaptic AMPA or NMDA receptors, while the effects of isoproterenol are mediated by facilitation of glutamate release from presynaptic terminals without effect on postsynaptic glutamate receptors. These two different mechanisms of modulation of excitatory synaptic transmission may improve the "signal-to-noise ratio" in cerebral cortex.
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Corteza Cerebral/citología , Ácido Glutámico/metabolismo , Células Piramidales/fisiología , Receptores Adrenérgicos beta/fisiología , Transmisión Sináptica/fisiología , Adrenérgicos/farmacología , Animales , Animales Recién Nacidos , Bicuculina/farmacología , Calcio/farmacología , Relación Dosis-Respuesta a Droga , Estimulación Eléctrica , Fármacos actuantes sobre Aminoácidos Excitadores/farmacología , Potenciales Postsinápticos Excitadores/efectos de los fármacos , Potenciales Postsinápticos Excitadores/fisiología , Femenino , Antagonistas del GABA/farmacología , Técnicas In Vitro , Masculino , Técnicas de Placa-Clamp/métodos , Terminales Presinápticos/efectos de los fármacos , Terminales Presinápticos/fisiología , Células Piramidales/citología , Células Piramidales/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Transmisión Sináptica/efectos de los fármacosRESUMEN
Experimentally induced changes in the central visual pathway were studied by using positron emission tomography in monkeys with unilateral hypertension glaucoma. In 2-[18F]fluoro-2-deoxy-glucose studies, monocular visual stimulation of the affected eye yielded significantly reduced neural responses in the occipital visuocortical areas. The response reduction was limited to the visual cortex ipsilateral to the affected eye, indicating the unique vulnerability of ipsilateral visual cortex in experimental unilateral glaucoma. In addition, in [11C]PK11195 positron emission tomography and immunohistochemical studies, selective accumulation of activated microglia, a sign of neural degeneration, was found bilaterally in lateral geniculate nuclei. The present findings establish the usefulness of noninvasive molecular imaging for early diagnosis of glaucoma by providing a sharper surrogate end point for an early phase of glaucoma.
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Cuerpos Geniculados/diagnóstico por imagen , Glaucoma/diagnóstico por imagen , Degeneración Nerviosa/diagnóstico por imagen , Lóbulo Occipital/diagnóstico por imagen , Animales , Radioisótopos de Carbono/metabolismo , Radioisótopos de Flúor/metabolismo , Fluorodesoxiglucosa F18/metabolismo , Cuerpos Geniculados/patología , Glaucoma/patología , Haplorrinos , Inmunohistoquímica , Isoquinolinas/metabolismo , Microglía/patología , Degeneración Nerviosa/patología , Lóbulo Occipital/patología , Oftalmoscopios , Tomografía de Emisión de Positrones , Corteza Visual/diagnóstico por imagenRESUMEN
We investigated how neural function is preserved or matured in the visual cortex of cats, following the induction of hydrocephalus by kaolin injection. In vivo optical imaging of intrinsic signals in 11-17-week-old hydrocephalic cats revealed orientation maps showing the orderly arrangement of preferred orientations when stimulated by grating stimuli at a low spatial frequency, whereas stimulus-evoked intrinsic signals in response to gratings at a high spatial frequency were often too weak to construct orientation maps. Furthermore, in two of the three hydrocephalic cats, initially deteriorated orientation maps became almost regular maps in the second imaging experiments conducted 8 and 11 weeks, respectively, after the first imaging. This indicates that, despite large structural deformation of the hydrocephalic brain, orientation maps are elaborated sufficiently after the age of 5-6 months, by which time the orientation map formation is usually completed in normal cats. Single unit recording from the decompressed visual cortex revealed that many neurons showed normal orientation selectivity, whereas the binocularity of these neurons was found to be reduced. These results suggested that the deformed visual cortex of hydrocephalic cats exhibits a high plasticity, retaining its functional organization.
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Mapeo Encefálico , Hidrocefalia/patología , Visión Ocular/fisiología , Corteza Visual/patología , Corteza Visual/fisiopatología , Potenciales de Acción/fisiología , Animales , Gatos , Diagnóstico por Imagen/métodos , Modelos Animales de Enfermedad , Lateralidad Funcional/fisiología , Hidrocefalia/inducido químicamente , Hidrocefalia/fisiopatología , Caolín , Orientación/fisiología , Estimulación Luminosa/métodos , Factores de Tiempo , Vías Visuales/fisiologíaRESUMEN
Neuronal growth-associated proteins, including superior cervical ganglia clone 10 (SCG10) family molecules, play roles in neurite outgrowth and network formation as well as structural and functional plasticity. The present ontogenetic study revealed that the expression of neuronal growth-associated proteins in the visual cortex (VC) exhibited a sharp peak in the early postnatal period when growing lateral geniculate nucleus (LGN) axon terminals segregate into the ocular dominance columns depending on retinal activity. We then hypothesized that SCG10 family molecules, known for catastrophic factors of microtubules, play important roles in the formation of ocular dominance columns. To test this hypothesis, we studied whether: (i) monocular blockade of retinal activity changed the SCG10 expression in LGN and VC and (ii) brain-derived neurotrophic factor (BDNF) cortical infusion modified the expression of SCG10 family molecules and the number of excitatory/inhibitory cortical synapses. Using northern blot and in situ hybridization, we revealed that: (i) silencing retinal activity with tetrodotoxin eye injections dynamically reduced the expression of SCG10 mRNA and (ii) it was enhanced by BDNF in VC and LGN of kittens but not adult cats. These findings suggest that cortical infusion of BDNF and retinal activity up-regulate the expression of SCG10 in the LGN and VC and that up-regulated SCG10 in turn initiates marked reorganization of the microtuble network, eventually resulting in increase in synapse formation in the VC.
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Factor Neurotrófico Derivado del Encéfalo/farmacología , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Cuerpos Geniculados/efectos de los fármacos , Factores de Crecimiento Nervioso/metabolismo , Corteza Visual/efectos de los fármacos , Factores de Edad , Animales , Animales Recién Nacidos , Northern Blotting/métodos , Gatos , Femenino , Cuerpos Geniculados/crecimiento & desarrollo , Cuerpos Geniculados/ultraestructura , Inmunohistoquímica/métodos , Hibridación in Situ/métodos , Masculino , Microscopía Electrónica de Transmisión/métodos , Modelos Biológicos , Tetrodotoxina/farmacología , Corteza Visual/crecimiento & desarrollo , Corteza Visual/ultraestructuraRESUMEN
To elucidate the effect of visual experience on the development of orientation maps, we conducted intrinsic signal optical imaging of the visual cortex of kittens that were continuously exposed to a single orientation through cylindrical-lens-fitted goggles under a freely moving condition starting at post-natal week 3. We observed a rapid reorganization of orientation maps, characterized by extensive representation of exposed orientations with reduced responsiveness to unexposed orientations. The over-representation of exposed orientation was marked for 1-2 weeks of goggle rearing. A longer period of goggle rearing, however, decreased the degree of over-representation, which still remained at a remarkable level. Dark rearing episodes daily interleaved between single orientation exposures moderated the over-representation effect. Unit recording from goggle-reared kittens showed preferred orientations consistent with optical imaging. Using c-Fos immunoreactivity mapping, we showed that the number of neurons strongly responding to the exposed orientation was 3 times larger in a goggle-reared cat than the number of neurons responding to the vertical orientation in a normal cat. Taken together, these results suggest that the reorganization of orientation maps was caused by the expansion of domains maximally responding to exposed orientation as well as the strong reduction of responses to unexposed orientations.
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Encéfalo/fisiología , Orientación/fisiología , Algoritmos , Animales , Mapeo Encefálico , Gatos , Electrodos Implantados , Electrofisiología , Procesamiento de Imagen Asistido por Computador , Inmunohistoquímica , Luz , Estimulación Luminosa , Proteínas Proto-Oncogénicas c-fos/biosíntesis , Proteínas Proto-Oncogénicas c-fos/fisiología , Visión Monocular/fisiologíaRESUMEN
Functional imaging technique using positron emission tomography (PET) has made it possible to localize functional brain regions in the human brain by detecting changes in regional cerebral blood flow (rCBF). Performing PET studies in the monkey will aid in integrating monkey electrophysiological research with human PET studies. We examined changes in rCBF during olfactory or combined olfactory and gustatory (flavour) stimulation using PET in the alert rhesus monkey. Olfactory or flavour stimulation with acetic acid or apple increased rCBF in the prepyriform area, substantia innominata and amygdala. Besides these areas, flavour stimulation increased rCBF in the anterior insula and frontal operculum, orbitofrontal cortex, inferior frontal gyrus and cerebellum. Apple odour or flavour stimuli increased rCBF in the inferior occipital gyrus in addition to the above areas. These findings suggest that the increases of rCBF in response to neural activities in the primary olfactory and gustatory cortices are detectable by the use of PET. In addition, regions activated by apple stimuli suggest that higher brain function might be detected with PET in the alert monkey.