Multidisciplinary, Multidisciplinaire, Sciences biologiques et medicales, Biological and medical sciences, Sciences biologiques fondamentales et appliquees. Psychologie, Fundamental and applied biological sciences. Psychology, Vertebres: systeme nerveux et organes des sens, Vertebrates: nervous system and sense organs, Oeil et annexes. Voies et centres visuels. Vision, Eye and associated structures. Visual pathways and centers. Vision, Electrophysiologie, Electrophysiology, Electrofisiología, Encéphale, Encephalon, Encéfalo, Mammalia, Rodentia, Récepteur glutamate, Glutamate receptor, Receptor glutámato, Système nerveux central, Central nervous system, Sistema nervioso central, Vertebrata, Voie visuelle, Visual pathway, Vía visual, Animal, Cortex visuel, Visual cortex, Corteza visual, Dendrite, Dendrita, Hyperpolarisation, Hyperpolarization, Hiperpolarización, Intracellulaire, Intracellular, Intracelular, Méthode patch clamp, Patch clamp method, Método patch clamp, Neurone pyramidal, Pyramidal neuron, Neurona piramidal, Orientation, Orientación, Potentiel action, Action potential, Potencial acción, Potentiel membrane, Membrane potential, Potencial membrana, Souris, Mouse, Ratón, Stimulation, Estimulación, Stimulus visuel, Visual stimulus, Estimulo visual, Sélectivité, Selectivity, and Selectividad

Neuronal dendrites are electrically excitable: they can generate regenerative events such as dendritic spikes in response to sufficiently strong synaptic input1―3. Although such events have been observed in many neuronal types4―9, it is not well understood how active dendrites contribute to the tuning of neuronal output in vivo. Here we show that dendritic spikes increase the selectivity of neuronal responses to the orientation of a visual stimulus (orientation tuning). We performed direct patch-clamp recordings from the dendrites of pyramidal neurons in the primary visual cortex of lightly anaesthetized and awake mice, during sensory processing. Visual stimulation triggered regenerative local dendritic spikes that were distinct from back-propagating action potentials. These events were orientation tuned and were suppressed by either hyperpolarization of membrane potential or intracellular blockade of NMD A (N-methyl-D-aspartate) receptors. Both of these manipulations also decreased the selectivity of subthreshold orientation tuning measured at the soma, thus linking dendritic regenerative events to somatic orientation tuning. Together, our results suggest that dendritic spikes that are triggered by visual input contribute to a fundamental cortical computation: enhancing orientation selectivity in the visual cortex. Thus, dendritic excitability is an essential component of behaviourally relevant computations in neurons.

Multidisciplinary, Multidisciplinaire, Sciences biologiques et medicales, Biological and medical sciences, Sciences biologiques fondamentales et appliquees. Psychologie, Fundamental and applied biological sciences. Psychology, Vertebres: systeme nerveux et organes des sens, Vertebrates: nervous system and sense organs, Motricité et voies motrices. Réflexes. Centres de contrôle des fonctions végétatives. Système vestibulaire et équilibration, Motor control and motor pathways. Reflexes. Control centers of vegetative functions. Vestibular system and equilibration, Oreille et annexes. Voies et centres auditifs. Audition. Organe vocal. Phonation. Emissions sonores. Echolocation, Ear and associated structures. Auditory pathways and centers. Hearing. Vocal organ. Phonation. Sound production. Echolocation, Encéphale, Encephalon, Encéfalo, Mammalia, Noyau gris central, Basal ganglion, Núcleo basal, Rodentia, Système nerveux central, Central nervous system, Sistema nervioso central, Vertebrata, Voie auditive, Auditory pathway, Vía auditiva, Animal, Contrôle moteur, Motor control, Control motor, Corps strié, Corpus striatum, Cuerpo estriado, Cortex auditif, Auditory cortex, Corteza auditiva, Discrimination, Discriminación, Neurone, Neuron, Neurona, Projection, Proyección, Rat, Rata, Stimulation, Estimulación, Tâche discrimination, Discrimination task, and Tarea discriminatoria

The neural pathways by which information about the acoustic world reaches the auditory cortex are well characterized, but how auditory representations are transformed into motor commands is not known. Here we use a perceptual decision-making task in rats to study this transformation. We demonstrate the role of corticostriatal projection neurons in auditory decisions by manipulating the activity of these neurons in rats performing an auditory frequency-discrimination task. Targeted channelrhodopsin-2 (ChR2)1,2-mediated stimulation of corticostriatal neurons during the task biased decisions in the direction predicted by the frequency tuning of the stimulated neurons, whereas archaerhodopsin-3 (Arch)3-mediated inactivation biased decisions in the opposite direction. Striatal projections are widespread in cortex and may provide a general mechanism for the control of motor decisions by sensory cortex.

Multidisciplinary, Multidisciplinaire, Sciences biologiques et medicales, Biological and medical sciences, Sciences biologiques fondamentales et appliquees. Psychologie, Fundamental and applied biological sciences. Psychology, Vertebres: systeme nerveux et organes des sens, Vertebrates: nervous system and sense organs, Somesthésie et voies somesthésiques (proprioception, extéroception, nociception); intéroception; électrolocation. Récepteurs sensoriels, Somesthesis and somesthetic pathways (proprioception, exteroception, nociception); interoception; electrolocation. Sensory receptors, Encéphale, Encephalon, Encéfalo, Perception, Percepción, Rodentia, Système nerveux central, Central nervous system, Sistema nervioso central, Vertebrata, Voie motrice, Motor pathway, Vía motora, Voie somesthésique, Somesthetic pathway, Vía somestésica, Activation, Activación, Animal, Calcium, Calcio, Comportement, Behavior, Conducta, Cortex cérébral, Cerebral cortex, Corteza cerebral, Cortex somatosensoriel, Somatosensory cortex, Corteza somatosensorial, Formation image, Imaging, Formación imagen, Mammalia, Neurone, Neuron, Neurona, Pensée, Thought, Pensamiento, Photon, Fotón, Projection, Proyección, Recrutement, Recruitment, Contratación, Souris, Mouse, and Ratón

In the mammalian neocortex, segregated processing streams are thought to be important for forming sensory representations of the environment1,2, but how local information in primary sensory cortex is transmitted to other distant cortical areas during behaviour is unclear. Here we show task-dependent activation of distinct, largely non-overlapping long-range projection neurons in the whisker region of primary somatosensory cortex (S1) in awake, behaving mice. Using two-photon calcium imaging, we monitored neuronal activity in anatomically identified S1 neurons projecting to secondary somatosensory (S2) or primary motor (M1) cortex in mice using their whiskers to perform a texture-discrimination task or a task that required them to detect the presence of an object at a certain location. Whisking-related cells were found among S2-projecting (S2P) but not M1-projecting (M1P) neurons. A higher fraction of S2P than M1P neurons showed touch-related responses during texture discrimination, whereas a higher fraction of M1P than S2P neurons showed touch-related responses during the detection task. In both tasks, S2P and M1P neurons could discriminate similarly between trials producing different behavioural decisions. However, in trials producing the same decision, S2P neurons performed better at discriminating texture, whereas M1P neurons were better at discriminating location. Sensory stimulus features alone were not sufficient to elicit these differences, suggesting that selective transmission of S1 information to S2 and M1 is driven by behaviour.

Multidisciplinary, Multidisciplinaire, Sciences biologiques et medicales, Biological and medical sciences, Sciences biologiques fondamentales et appliquees. Psychologie, Fundamental and applied biological sciences. Psychology, Vertebres: systeme nerveux et organes des sens, Vertebrates: nervous system and sense organs, Encéphale, Encephalon, Encéfalo, Récepteur glutamate, Glutamate receptor, Receptor glutámato, Système nerveux central, Central nervous system, Sistema nervioso central, Dendrite, Dendrita, Hyperpolarisation, Hyperpolarization, Hiperpolarización, Intracellulaire, Intracellular, Intracelular, NMDA, Neurone sensoriel, Sensory neuron, Neurona sensorial, Neurone étoilé, Stellate neuron, Neurona estrellada, Récepteur NMDA, NMDA receptor, Receptor NMDA, Sélectivité, Selectivity, and Selectividad

Layer 4 neurons in primary sensory cortices receive direct sensory information from the external world1,2. A general feature of these neurons is their selectivity to specific features of the sensory stimulation3―5. Various theories try to explain the manner in which these neurons are driven by their incoming sensory information6―11. In all of these theories neurons are regarded as simple elements summing small biased inputs to create tuned output through the axosomatic amplification mechanism12. However, the possible role of active dendritic integration13―15 in further amplifying the sensory responses and sharpening the tuning curves of neurons16―19 is disregarded. Our findings show that dendrites of layer 4 spiny stellate neurons in the barrel cortex can generate local and global multi-branch N-methyl-D-aspartate (NMDA) spikes, which are the main regenerative events in these dendrites. In turn, these NMDA receptor (NMDAR) regenerative mechanisms can sum supralinearly the coactivated thalamocortical and corticocortical inputs. Using in vivo whole-cell recordings combined with an intracellular NMDAR blocker and membrane hyperpolarization, we show that dendritic NMDAR-dependent regenerative responses contribute substantially to the angular tuning of layer 4 neurons by preferentially amplifying the preferred angular directions over non-preferred angles. Taken together, these findings indicate that dendritic NMDAR regenerative amplification mechanisms contribute markedly to sensory responses and critically determine the tuning of cortical neurons.

Multidisciplinary, Multidisciplinaire, Sciences biologiques et medicales, Biological and medical sciences, Sciences biologiques fondamentales et appliquees. Psychologie, Fundamental and applied biological sciences. Psychology, Vertebres: systeme nerveux et organes des sens, Vertebrates: nervous system and sense organs, Catécholamine, Catecholamine, Catecolamina, Electrophysiologie, Electrophysiology, Electrofisiología, Neurotransmetteur, Neurotransmitter, Neurotransmisor, Système nerveux central, Central nervous system, Sistema nervioso central, Vertebrata, Aire tegmentaire ventrale, Ventral tegmental area, Area tegmental ventral, Apprentissage moteur, Motor learning, Aprendizaje motor, Corps strié, Corpus striatum, Cuerpo estriado, Dopamine, Dopamina, Encéphale, Encephalon, Encéfalo, GABA, Libération, Release, Liberación, Locus niger, Locus níger, Mammalia, Neurone dopaminergique, Dopaminergic neuron, Neurona dopaminérgica, Planification, Planning, Planificación, Projection, Proyección, Récompense, Reward, and Recompensa

The substantia nigra pars compacta and ventral tegmental area contain the two largest populations of dopamine-releasing neurons in the mammalian brain. These neurons extend elaborate projections in the striatum, a large subcortical structure implicated in motor planning and reward-based learning. Phasic activation of dopaminergic neurons in response to salient or reward-predicting stimuli is thought to modulate striatal output through the release of dopamine to promote and reinforce motor action1-4. Here we show that activation of dopamine neurons in striatal slices rapidly inhibits action potential firing in both direct- and indirect-pathway striatal projection neurons through vesicular release of the inhibitory transmitter GABA (y-aminobutyric acid). GABA is released directly from dopaminergic axons but in a manner that is independent of the vesicular GABA transporter VGAT. Instead, GABA release requires activity of the vesicular monoamine transporter VMAT2, which is the vesicular transporter for dopamine. Furthermore, VMAT2 expression in GABAergic neurons lacking VGAT is sufficient to sustain GABA release. Thus, these findings expand the repertoire of synaptic mechanisms used by dopamine neurons to influence basal ganglia circuits, show a new substrate whose transport is dependent on VMAT2 and demonstrate that GABA can function as a bona fide co-transmitter in monoaminergic neurons.

Multidisciplinary, Multidisciplinaire, Sciences biologiques et medicales, Biological and medical sciences, Sciences biologiques fondamentales et appliquees. Psychologie, Fundamental and applied biological sciences. Psychology, Vertebres: systeme nerveux et organes des sens, Vertebrates: nervous system and sense organs, Oeil et annexes. Voies et centres visuels. Vision, Eye and associated structures. Visual pathways and centers. Vision, Encéphale, Encephalon, Encéfalo, Jonction cellulaire, Cell junction, Unión celular, Rodentia, Système nerveux central, Central nervous system, Sistema nervioso central, Vertebrata, Voie visuelle, Visual pathway, Vía visual, Animal, Calcium, Calcio, Cortex cérébral, Cerebral cortex, Corteza cerebral, Cortex visuel, Visual cortex, Corteza visual, Développement, Development, Desarrollo, Formation image, Imaging, Formación imagen, Mammalia, Neurone, Neuron, Neurona, Orientation, Orientación, Photon, Fotón, Protéine fluorescente verte, Green fluorescent protein, Proteína fluorescente verde, Préférence, Preference, Preferencia, Souris, Mouse, Ratón, Stimulus visuel, Visual stimulus, Estimulo visual, Sélectivité, Selectivity, and Selectividad

A fundamental feature of the mammalian neocortex is its columnar organization'. In the visual cortex, functional columns consisting of neurons with similar orientation preferences have been characterized extensively2―4, but how these columns are constructed during development remains unclear5. The radial unit hypothesis6 posits that the ontogenetic columns formed by clonally related neurons migrating along the same radial glial fibre during corticogenesis7 provide the basis for functional columns in adult neocortex1. However, a direct correspondence between the ontogenetic and functional columns has not been demonstrated8. Here we show that, despite the lack of a discernible orientation map in mouse visual cortex4,9,10, sister neurons in the same radial clone exhibit similar orientation preferences. Using a retroviral vector encoding green fluorescent protein to label radial clones of excitatory neurons, and in vivo two-photon calcium imaging to measure neuronal response properties, we found that sister neurons preferred similar orientations whereas nearby non-sister neurons showed no such relationship. Interestingly, disruption of gap junction coupling by viral expression of a dominant-negative mutant of Cx26 (also known as Gjb2) or by daily administration of a gap junction blocker, carbenoxolone, during the first postnatal week greatly diminished the functional similarity between sister neurons, suggesting that the maturation of ontogenetic into functional columns requires intercellular communication through gap junctions. Together with the recent finding of preferential excitatory connections among sister neurons, our results support the radial unit hypothesis and unify the ontogenetic and functional columns in the visual cortex.

Multidisciplinary, Multidisciplinaire, Sciences biologiques et medicales, Biological and medical sciences, Sciences biologiques fondamentales et appliquees. Psychologie, Fundamental and applied biological sciences. Psychology, Vertebres: systeme nerveux et organes des sens, Vertebrates: nervous system and sense organs, Catécholamine, Catecholamine, Catecolamina, Neurotransmetteur, Neurotransmitter, Neurotransmisor, Système nerveux central, Central nervous system, Sistema nervioso central, Calcium, Calcio, Corpora pedunculata, Dopamine, Dopamina, Encéphale, Encephalon, Encéfalo, Formation image, Imaging, Formación imagen, Mémoire associative, Associative memory, Memoria asociativa, Neurone dopaminergique, Dopaminergic neuron, Neurona dopaminérgica, Renforcement, Reinforcement, Reforzamiento, Récompense, Reward, Recompensa, Stimulus, and Estímulo

Animals approach stimuli that predict a pleasant outcome'. After the paired presentation of an odour and a reward, Drosophila melanogaster can develop a conditioned approach towards that odour2,3. Despite recent advances in understanding the neural circuits for associative memory and appetitive motivation4, the cellular mechanisms for reward processing in the fly brain are unknown. Here we show that a group of dopamine neurons in the protocerebral anterior medial (PAM) cluster signals sugar reward by transient activation and inactivation of target neurons in intact behaving flies. These dopamine neurons are selectively required for the reinforcing property of, but not a reflexive response to, the sugar stimulus. In vivo calcium imaging revealed that these neurons are activated by sugar ingestion and the activation is increased on starvation. The output sites of the PAM neurons are mainly localized to the medial lobes of the mushroom bodies (MBs), where appetitive olfactory associative memory is formed5,6. We therefore propose that the PAM cluster neurons endow a positive predictive value to the odour in the MBs. Dopamine in insects is known to mediate aversive reinforcement signals5,7―11. Our results highlight the cellular specificity underlying the various roles of dopamine and the importance of spatially segregated local circuits within the MBs.

Multidisciplinary, Multidisciplinaire, Sciences biologiques et medicales, Biological and medical sciences, Sciences biologiques fondamentales et appliquees. Psychologie, Fundamental and applied biological sciences. Psychology, Vertebres: systeme nerveux et organes des sens, Vertebrates: nervous system and sense organs, Encéphale, Encephalon, Encéfalo, Système nerveux central, Central nervous system, Sistema nervioso central, Ablation, Ablación, Adaptation, Adaptación, Cognition, Cognición, Comportement, Behavior, Conducta, Contrôle cognitif, Cognitive control, Control cognitivo, Cortex cingulaire, Cingulate cortex, Corteza cingular, Homme, Human, Hombre, Imagerie fonctionnelle, Functional imaging, Imaginería funcional, Lobe frontal, Frontal lobe, Lóbulo frontal, Neurone, Neuron, Neurona, Récompense, Reward, and Recompensa

The ability to optimize behavioural performance when confronted with continuously evolving environmental demands is a key element of human cognition. The dorsal anterior cingulate cortex (dACC), which lies on the medial surface of the frontal lobes, is important in regulating cognitive control. Hypotheses about its function include guiding reward-based decision making', monitoring for conflict between competing responses2 and predicting task difficulty3. Precise mechanisms of dACC function remain unknown, however, because of the limited number of human neurophysiological studies. Here we use functional imaging and human single-neuron recordings to show that the firing of individual dACC neurons encodes current and recent cognitive load. We demonstrate that the modulation of current dACC activity by previous activity produces a behavioural adaptation that accelerates reactions to cues of similar difficulty to previous ones, and retards reactions to cues of different difficulty. Furthermore, this conflict adaptation, or Gratton effect2,4, is abolished after surgically targeted ablation of the dACC. Our results demonstrate that the dACC provides a continuously updated prediction of expected cognitive demand to optimize future behavioural responses. In situations with stable cognitive demands, this signal promotes efficiency by hastening responses, but in situations with changing demands it engenders accuracy by delaying responses.

Multidisciplinary, Multidisciplinaire, Sciences biologiques et medicales, Biological and medical sciences, Sciences biologiques fondamentales et appliquees. Psychologie, Fundamental and applied biological sciences. Psychology, Vertebres: anatomie et physiologie, organisme dans son ensemble ou etude de plusieurs organes ou systemes, Vertebrates: anatomy and physiology, studies on body, several organs or systems, Chronobiologie, Chronobiology, Vertebres: systeme nerveux et organes des sens, Vertebrates: nervous system and sense organs, Sommeil. Vigilance, Sleep. Vigilance, Appareil visuel, Visual system, Aparato visual, Encéphale, Encephalon, Encéfalo, Glucocorticoïde, Glucocorticoid, Glucocorticoide, Hormone surrénalienne, Adrenal hormone, Hormona suprarrenal, Mammalia, Oeil, Eye, Ojo, Processus acquisition, Acquisition process, Proceso adquisición, Rodentia, Rythme biologique, Biological rhythm, Ritmo biológico, Système nerveux central, Central nervous system, Sistema nervioso central, Vertebrata, Animal, Apprentissage, Learning, Aprendizaje, Cognition, Cognición, Comportement, Behavior, Conducta, Corticostérone, Corticosterone, Corticosterona, Cycle veille sommeil, Sleep wake cycle, Ciclo sueño vigilia, Hippocampe, Hippocampus, Hipocampo, Insomnie, Insomnia, Insomnio, Neurone, Neuron, Neurona, Rythme circadien, Circadian rhythm, Ritmo circadiano, Sommeil, Sleep, Sueño, Souris, Mouse, Ratón, Trouble cognitif, Cognitive disorder, Trastorno cognitivo, Trouble de l'humeur, Mood disorder, Trastorno humor, Mélanopsine, and Melanopsin

The daily solar cycle allows organisms to synchronize their circadian rhythms and sleep-wake cycles to the correct temporal niche'. Changes in day-length, shift-work, and transmeridian travel lead to mood alterations and cognitive function deficits2. Sleep deprivation and circadian disruption underlie mood and cognitive disorders associated with irregular light schedules2. Whether irregular light schedules directly affect mood and cognitive functions in the context of normal sleep and circadian rhythms remains unclear. Here we show, using an aberrant light cycle that neither changes the amount and architecture of sleep nor causes changes in the circadian timing system, that light directly regulates mood-related behaviours and cognitive functions in mice. Animals exposed to the aberrant light cycle maintain daily corticosterone rhythms, but the overall levels of corticosterone are increased. Despite normal circadian and sleep structures, these animals show increased depression-like behaviours and impaired hippocampal long-term potentiation and learning. Administration of the antidepressant drugs fluoxetine or desipramine restores learning in mice exposed to the aberrant light cycle, suggesting that the mood deficit precedes the learning impairments. To determine the retinal circuits underlying this impairment of mood and learning, we examined the behavioural consequences of this light cycle in animals that lack intrinsically photosensitive retinal ganglion cells. In these animals, the aberrant light cycle does not impair mood and learning, despite the presence of the conventional retinal ganglion cells and the ability of these animals to detect light for image formation. These findings demonstrate the ability of light to influence cognitive and mood functions directly through intrinsically photosensitive retinal ganglion cells.

Multidisciplinary, Multidisciplinaire, Sciences biologiques et medicales, Biological and medical sciences, Sciences biologiques fondamentales et appliquees. Psychologie, Fundamental and applied biological sciences. Psychology, Vertebres: systeme nerveux et organes des sens, Vertebrates: nervous system and sense organs, Appareil olfactif et olfaction. Appareil gustatif et gustation, Olfactory system and olfaction. Gustatory system and gustation, Système nerveux central, Central nervous system, Sistema nervioso central, Voie olfactive, Olfactory pathway, Vía olfatoria, Axone, Axon, Axón, Bulbe olfactif, Olfactory bulb, Bulbo olfatorio, Cortex olfactif, Olfactory cortex, Corteza olfativa, Encéphale, Encephalon, Encéfalo, Intégration information, Information integration, Integración información, Neurone, Neuron, Neurona, Olfaction, Olfación, Projection, Proyección, Stéréotypie, Stereotypy, and Estereotipia

Sensory information may be represented in the brain by stereotyped mapping of axonal inputs or by patterning that varies between individuals. In olfaction, a stereotyped map is evident in the first sensory processing centre, the olfactory bulb (OB), where different odours elicit activity in unique combinatorial patterns of spatially invariant glomeruli1,2. Activation of each glomerulus is relayed to higher cortical processing centres by a set of ∼20―50 'homotypic' mitral and tufted (MT) neurons3. In the cortex, target neurons integrate information from multiple glomeruli to detect distinct features of chemically diverse odours4―6. How this is accomplished remains unclear, perhaps because the cortical mapping of glomerular information by individual MT neurons has not been described. Here we use new viral tracing and three-dimensional brain reconstruction methods to compare the cortical projections of defined sets of MT neurons. We show that the gross-scale organization of the OB is preserved in the patterns of axonal projections to one processing centre yet reordered in another, suggesting that distinct coding strategies may operate in different targets. However, at the level of individual neurons neither glomerular order nor stereotypy is preserved in either region. Rather, homotypic MT neurons from the same glomerulus innervate broad regions that differ between individuals. Strikingly, even in the same animal, MT neurons exhibit extensive diversity in wiring; axons of homotypic MT pairs diverge from each other, emit primary branches at distinct locations and 70-90% of branches of homotypic and heterotypic pairs are nonoverlapping. This pronounced reorganization of sensory maps in the cortex offers an anatomic substrate for expanded combinatorial integration of information from spatially distinct glomeruli and predicts an unanticipated role for diversification of otherwise similar output neurons.

Multidisciplinary, Multidisciplinaire, Sciences biologiques et medicales, Biological and medical sciences, Sciences biologiques fondamentales et appliquees. Psychologie, Fundamental and applied biological sciences. Psychology, Vertebres: systeme nerveux et organes des sens, Vertebrates: nervous system and sense organs, Encéphale, Encephalon, Encéfalo, Mammalia, Rodentia, Système nerveux central, Central nervous system, Sistema nervioso central, Vertebrata, Voie visuelle, Visual pathway, Vía visual, Anatomie, Anatomy, Anatomía, Animal, Calcium, Calcio, Cortex cérébral, Cerebral cortex, Corteza cerebral, Cortex visuel, Visual cortex, Corteza visual, Imagerie fonctionnelle, Functional imaging, Imaginería funcional, Neurone intermédiaire, Interneuron, Neurona intermediaria, Orientation spatiale, Spatial orientation, Orientación espacial, Perception, Percepción, Photon, Fotón, Psychométrie, Psychometrics, Psicometría, Relation structure fonction, Structure function relationship, Relación estructura función, Souris, Mouse, Ratón, Vision, and Visión

In the cerebral cortex, local circuits consist of tens of thousands of neurons, each of which makes thousands of synaptic connections. Perhaps the biggest impediment to understanding these networks is that we have no wiring diagrams of their interconnections. Even if we had a partial or complete wiring diagram, however, understanding the network would also require information about each neuron's function. Here we show that the relationship between structure and function can be studied in the cortex with a combination of in vivo physiology and network anatomy. We used two-photon calcium imaging to characterize a functional property—the preferred stimulus orientation—of a group of neurons in the mouse primary visual cortex. Large-scale electron microscopy of serial thin sections was then used to trace a portion of these neurons' local network. Consistent with a prediction from recent physiological experiments, inhibitory interneurons received convergent anatomical input from nearby excitatory neurons with a broad range of preferred orientations, although weak biases could not be rejected.

Multidisciplinary, Multidisciplinaire, Sciences biologiques et medicales, Biological and medical sciences, Sciences biologiques fondamentales et appliquees. Psychologie, Fundamental and applied biological sciences. Psychology, Vertebres: systeme nerveux et organes des sens, Vertebrates: nervous system and sense organs, Appareil olfactif et olfaction. Appareil gustatif et gustation, Olfactory system and olfaction. Gustatory system and gustation, Homme, Human, Hombre, Névroglie, Neuroglia, Perception, Percepción, Système nerveux central, Central nervous system, Sistema nervioso central, Vertebrata, Voie olfactive, Olfactory pathway, Vía olfatoria, Adulte, Adult, Adulto, Astrocyte, Astrocito, Bulbe olfactif, Olfactory bulb, Bulbo olfatorio, Cellule souche, Stem cell, Célula primitiva, Contraste, Contrast, Descendance, Progeny, Descendencia, Encéphale, Encephalon, Encéfalo, In vitro, Mammalia, Neurone, Neuron, Neurona, Nombre, Number, Número, Nourrisson, Infant, Lactante, Olfaction, and Olfación

The subventricular zone of many adult non-human mammals generates large numbers of new neurons destined for the olfactory bulb1-6. Along the walls of the lateral ventricles, immature neuronal progeny migrate in tangentially oriented chains that coalesce into a rostral migratory stream (RMS) connecting the subventricular zone to the olfactory bulb. The adult human subventricular zone, in contrast, contains a hypocellular gap layer separating the ependymal lining from a periventricular ribbon of astrocytes7. Some of these subventricular zone astrocytes can function as neural stem cells in vitro, but their function in vivo remains controversial. An initial report found few subventricular zone proliferating cells and rare migrating immature neurons in the RMS of adult humans7. In contrast, a subsequent study indicated robust proliferation and migration in the human subventricular zone and RMS8,9. Here we find that the infant human subventricular zone and RMS contain an extensive corridor of migrating immature neurons before 18 months of age but, contrary to previous reports8, this germinal activity subsides in older children and is nearly extinct by adult-hood. Surprisingly, during this limited window of neurogenesis, not all new neurons in the human subventricular zone are destined for the olfactory bulb—we describe a major migratory pathway that targets the prefrontal cortex in humans. Together, these findings reveal robust streams of tangentially migrating immature neurons in human early postnatal subventricular zone and cortex. These pathways represent potential targets of neurological injuries affecting neonates.

Multidisciplinary, Multidisciplinaire, Sciences biologiques et medicales, Biological and medical sciences, Sciences biologiques fondamentales et appliquees. Psychologie, Fundamental and applied biological sciences. Psychology, Vertebres: systeme nerveux et organes des sens, Vertebrates: nervous system and sense organs, Sciences medicales, Medical sciences, Neurologie, Neurology, Maladies dégénératives et hérédodégénératives du système nerveux. Leucodystrophies. Maladies à prions, Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases, Encéphale, Encephalon, Encéfalo, Mammalia, Pathologie du système nerveux, Nervous system diseases, Sistema nervioso patología, Rodentia, Système nerveux central, Central nervous system, Sistema nervioso central, Vertebrata, Animal, Calcium, Calcio, Canal ionique, Ionic channel, Canal iónico, Canal membranaire, Membrane channel, Canal membranario, Dépolarisation, Depolarization, Despolarización, Homme, Human, Hombre, Locus niger, Locus níger, Maladie de Parkinson, Parkinson disease, Parkinson enfermedad, Maladie dégénérative, Degenerative disease, Enfermedad degenerativa, Membrane plasmique, Plasma membrane, Membrana plasmática, Mitochondrie, Mitochondria, Mitocondria, Neurone dopaminergique, Dopaminergic neuron, Neurona dopaminérgica, Perméabilité, Permeability, Permeabilidad, Protéine, Protein, Proteína, Souris, Mouse, Ratón, Stress, Estrés, Sénescence, Senescence, and Senescencia

Parkinson's disease is a pervasive, ageing-related neurodegenerative disease the cardinal motor symptoms of which reflect the loss of a small group of neurons, the dopaminergic neurons in the substantia nigra pars compacta' (SNc). Mitochondrial oxidant stress is widely viewed as being responsible for this loss2, but why these particular neurons should be stressed is a mystery. Here we show, using trans- ( genic mice that expressed a redox-sensitive variant of green fluor- i escent protein targeted to the mitochondrial matrix, that the engagement of plasma membrane L-type calcium channels during normal autonomous pacemaking created an oxidant stress that was specific to vulnerable SNc dopaminergic neurons. The oxidant stress engaged defences that induced transient, mild mitochondrial depolarization or uncoupling. The mild uncoupling was not affected by deletion of cyclophilin D, which is a component of the permeability transition pore, but was attenuated by genipin and purine nucleotides, which are antagonists of cloned uncoupling proteins. Knocking out DJ-1 (also known as PARK7 in humans and Park7 in mice), which is a gene associated with an early-onset form of Parkinson's disease, downregulated the expression of two uncoupling proteins (UCP4 (SLC25A27) and UCP5 (SLC25A14)), compromised calcium- ( induced uncoupling and increased oxidation of matrix proteins specifically in SNc dopaminergic neurons. Because drugs approved for human use can antagonize calcium entry through L-type channels, these results point to a novel neuroprotective strategy for both idio- ( pathic and familial forms of Parkinson's disease.

Multidisciplinary, Multidisciplinaire, Sciences biologiques et medicales, Biological and medical sciences, Sciences biologiques fondamentales et appliquees. Psychologie, Fundamental and applied biological sciences. Psychology, Vertebres: systeme nerveux et organes des sens, Vertebrates: nervous system and sense organs, Oeil et annexes. Voies et centres visuels. Vision, Eye and associated structures. Visual pathways and centers. Vision, Appareil visuel, Visual system, Aparato visual, Electrophysiologie, Electrophysiology, Electrofisiología, Système nerveux central, Central nervous system, Sistema nervioso central, Cognition, Cognición, Contrôle volontaire, Voluntary control, Control voluntario, Encéphale, Encephalon, Encéfalo, Homme, Human, Hombre, Lobe temporal, Temporal lobe, Lóbulo temporal, Mode décharge, Discharge pattern, Forma descarga, Neurone, Neuron, Neurona, Oeil, Eye, Ojo, Rumination, and Rumia

Daily life continually confronts us with an exuberance of external, sensory stimuli competing with a rich stream of internal deliberations, plans and ruminations. The brain must select one or more of these for further processing. How this competition is resolved across multiple sensory and cognitive regions is not known; nor is it clear how internal thoughts and attention regulate this competition1-4. Recording from single neurons in patients implanted with intracranial electrodes for clinical reasons5-9, here we demonstrate that humans can regulate the activity of their neurons in the medial temporal lobe (MTL) to alter the outcome of the contest between external images and their internal representation. Subjects looked at a hybrid superposition of two images representing familiar individuals, landmarks, objects or animals and had to enhance one image at the expense of the other, competing one. Simultaneously, the spiking activity of their MTL neurons in different subregions and hemispheres was decoded in real time to control the content of the hybrid. Subjects reliably regulated, often on the first trial, the firing rate of their neurons, increasing the rate of some while simultaneously decreasing the rate of others. They did so by focusing onto one image, which gradually became clearer on the computer screen in front of their eyes, and thereby overriding sensory input. On the basis of the firing of these MTL neurons, the dynamics of the competition between visual images in the subject's mind was visualized on an external display.

Multidisciplinary, Multidisciplinaire, Sciences biologiques et medicales, Biological and medical sciences, Sciences biologiques fondamentales et appliquees. Psychologie, Fundamental and applied biological sciences. Psychology, Vertebres: systeme nerveux et organes des sens, Vertebrates: nervous system and sense organs, Oeil et annexes. Voies et centres visuels. Vision, Eye and associated structures. Visual pathways and centers. Vision, Encéphale, Encephalon, Encéfalo, Système nerveux central, Central nervous system, Sistema nervioso central, Voie visuelle, Visual pathway, Vía visual, Calcium, Calcio, Cortex visuel, Visual cortex, Corteza visual, Dendrite, Dendrita, Electrophysiologie, Electrophysiology, Electrofisiología, Formation image, Imaging, Formación imagen, Mode décharge, Discharge pattern, Forma descarga, Neurone sensoriel, Sensory neuron, Neurona sensorial, Orientation, Orientación, Photon, Fotón, Préférence, Preference, Preferencia, Stimulus, and Estímulo

In sensory cortex regions, neurons are tuned to specific stimulus features. For example, in the visual cortex, many neurons fire predominantly in response to moving objects of a preferred orientation. However, the characteristics of the synaptic input that cortical neurons receive to generate their output firing pattern remain unclear. Here we report a novel approach for the visualization and functional mapping of sensory inputs to the dendrites of cortical neurons in vivo. By combining high-speed two-photon imaging with electrophysiological recordings, we identify local subthreshold calcium signals that correspond to orientation-specific synaptic inputs. We find that even inputs that share the same orientation preference are widely distributed throughout the dendritic tree. At the same time, inputs of different orientation preference are interspersed, so that adjacent dendritic segments are tuned to distinct orientations. Thus, orientation-tuned neurons can compute their characteristic firing pattern by integrating spatially distributed synaptic inputs coding for multiple stimulus orientations.

Multidisciplinary, Multidisciplinaire, Sciences biologiques et medicales, Biological and medical sciences, Sciences biologiques fondamentales et appliquees. Psychologie, Fundamental and applied biological sciences. Psychology, Vertebres: systeme nerveux et organes des sens, Vertebrates: nervous system and sense organs, Electrophysiologie, Electrophysiology, Electrofisiología, Processus acquisition, Acquisition process, Proceso adquisición, Vertebrata, Apprentissage, Learning, Aprendizaje, Comportement, Behavior, Conducta, Encéphale, Encephalon, Encéfalo, Homme, Human, Hombre, Lobe temporal, Temporal lobe, Lóbulo temporal, Mammalia, Mémoire, Memory, Memoria, Neurone, Neuron, Neurona, Oscillation, Oscilación, Plasticité synaptique, Synaptic plasticity, Plasticidad sináptica, Potentiel action, Action potential, Potencial acción, Potentiel champ, Field potential, Potencial campo, Synapse, Sinapsis, Système nerveux central, Central nervous system, and Sistema nervioso central

Learning from novel experiences is a major task of the central nervous system. In mammals, the medial temporal lobe is crucial for this rapid form of learning1. The modification of synapses and neuronal circuits through plasticity is thought to underlie memory formation2. The induction of synaptic plasticity is favoured by coordinated action-potential timing across populations of neurons3. Such coordinated activity of neural populations can give rise to oscillations of different frequencies, recorded in local field potentials. Brain oscillations in the theta frequency range (3-8Hz) are often associated with the favourable induction of synaptic plasticity as well as behavioural memory4. Here we report the activity of single neurons recorded together with the local field potential in humans engaged in a learning task. We show that successful memory formation in humans is predicted by a tight coordination of spike timing with the local theta oscillation. More stereotyped spiking predicts better memory, as indicated by higher retrieval confidence reported by subjects. These findings provide a link between the known modulation of theta oscillations by many memory-modulating behaviours and circuit mechanisms of plasticity.

Multidisciplinary, Multidisciplinaire, Sciences biologiques et medicales, Biological and medical sciences, Sciences biologiques fondamentales et appliquees. Psychologie, Fundamental and applied biological sciences. Psychology, Vertebres: systeme nerveux et organes des sens, Vertebrates: nervous system and sense organs, Système nerveux central, Central nervous system, Sistema nervioso central, Vertebrata, Axone, Axon, Axón, Cortex cérébral, Cerebral cortex, Corteza cerebral, Encéphale, Encephalon, Encéfalo, Formation image, Imaging, Formación imagen, Imagerie RMN, Nuclear magnetic resonance imaging, Imaginería RMN, Imagerie fonctionnelle, Functional imaging, Imaginería funcional, Mammalia, Neurone, Neuron, Neurona, Projection, Proyección, Stimulation, Estimulación, Stimulus électrique, Electrical stimulus, Estímulo eléctrico, Thalamus, and Tálamo

Despite a rapidly-growing scientific and clinical brain imaging literature based on functional magnetic resonance imaging (fMRI) using blood oxygenation level-dependent (BOLD)1 signals, it remains controversial whether BOLD signals in a particular region can be caused by activation of local excitatory neurons2. This difficult question is central to the interpretation and utility of BOLD, with major significance for fMRI studies in basic research and clinical applications3. Using a novel integrated technology unifying optogenetic4―13 control of inputs with high-field fMRI signal readouts, we show here that specific stimulation of local CaMKIIα-expressing excitatory neurons, either in the neocortex or thalamus, elicits positive BOLD signals at the stimulus location with classical kinetics. We also show that optogenetic fMRI (ofMRI) allows visualization of the causal effects of specific cell types defined not only by genetic identity and cell body location, but also by axonal projection target. Finally, we show that ofMRI within the living and intact mammalian brain reveals BOLD signals in downstream targets distant from the stimulus, indicating that this approach can be used to map the global effects of controlling a local cell population. In this respect, unlike both conventional fMRI studies based on correlations and fMRI with electrical stimulation that will also directly drive afferent and nearby axons, this ofMRI approach provides causal information about the global circuits recruited by defined local neuronal activity patterns. Together these findings provide an empirical foundation for the widely-used fMRI BOLD signal, and the features of ofMRI define a potent tool that may be suitable for functional circuit analysis as well as global phenotyping of dysfunctional circuitry.

Multidisciplinary, Multidisciplinaire, Sciences biologiques et medicales, Biological and medical sciences, Sciences biologiques fondamentales et appliquees. Psychologie, Fundamental and applied biological sciences. Psychology, Vertebres: systeme nerveux et organes des sens, Vertebrates: nervous system and sense organs, Encéphale, Encephalon, Encéfalo, Rodentia, Système nerveux central, Central nervous system, Sistema nervioso central, Vertebrata, Animal, Cortex cérébral, Cerebral cortex, Corteza cerebral, Développement, Development, Desarrollo, Mammalia, Neurogenèse, Neurogenesis, Neurogénesis, Neurone, Neuron, Neurona, Protéine fluorescente verte, Green fluorescent protein, Proteína fluorescente verde, Préférence, Preference, Preferencia, Souris, Mouse, Ratón, Substance blanche, White matter, Substancia blanca, Synapse, and Sinapsis

Neurons in the mammalian neocortex are organized into functional columns1,2. Within a column, highly specific synaptic connections are formed to ensure that similar physiological properties are shared by neuron ensembles spanning from the pia to the white matter. Recent studies indicate that synaptic connectivity in the neocortex is sparse and highly specific3-8 to allow even adjacent neurons to convey information independently9-12. How this fine-scale microcircuit is constructed to create a functional columnar architecture at the level of individual neurons largely remains a mystery. Here we investigate whether radial clones of excitatory neurons arising from the same mother cell in the developing neocortex serve as a substrate for the formation of this highly specific microcircuit. We labelled ontogenetic radial clones of excitatory neurons in the mouse neocortex by in utero intraventricular injection of enhanced green fluorescent protein (EGFP)-expressing retroviruses around the onset of the peak phase of neocortical neurogenesis. Multiple-electrode whole-cell recordings were performed to probe synapse formation among these EGFP-labelled sister excitatory neurons in radial clones and the adjacent non-siblings during postnatal stages. We found that radially aligned sister excitatory neurons have a propensity for developing unidirectional chemical synapses with each other rather than with neighbouring non-siblings. Moreover, these synaptic connections display the same interlaminar directional preference as those observed in the mature neocortex. These results indicate that specific microcircuits develop preferentially within ontogenetic radial clones of excitatory neurons in the developing neocortex and contribute to the emergence of functional columnar micro-architectures in the mature neocortex.

Multidisciplinary, Multidisciplinaire, Sciences biologiques et medicales, Biological and medical sciences, Sciences biologiques fondamentales et appliquees. Psychologie, Fundamental and applied biological sciences. Psychology, Vertebres: systeme nerveux et organes des sens, Vertebrates: nervous system and sense organs, Oeil et annexes. Voies et centres visuels. Vision, Eye and associated structures. Visual pathways and centers. Vision, Noyau gris central, Basal ganglion, Núcleo basal, Système nerveux central, Central nervous system, Sistema nervioso central, Voie visuelle, Visual pathway, Vía visual, Connexion corticocorticale, Corticocortical connection, Conexión corticocortical, Corps strié, Corpus striatum, Cuerpo estriado, Encéphale, Encephalon, Encéfalo, Monosynaptique, Monosynaptic, Monosináptico, Neurone postsynaptique, Postsynaptic neuron, Neurona postsináptica, Neurone présynaptique, Presynaptic neuron, Neurona presináptica, Neurone pyramidal, Pyramidal neuron, Neurona piramidal, Souscortex, Subcortex, Subcorteza, Tubercule quadrijumeau antérieur, Colliculus superior, and Tubérculo cuadrigémino anterior

Cortical columns generate separate streams of information that are distributed to numerous cortical and subcortical brain regions1. We asked whether local intracortical circuits reflect these different processing streams by testing whether the intracortical connectivity among pyramidal neurons reflects their long-range axonal targets. We recorded simultaneously from up to four retrogradely labelled pyramidal neurons that projected to the superior colliculus, the contralateral striatum or the contralateral cortex to assess their synaptic connectivity. Here we show that the probability of synaptic connection depends on the functional identities of both the presynaptic and postsynaptic neurons. We first found that the frequency of monosynaptic connections among corticostriatal pyramidal neurons is significantly higher than among corticocortical or corticotectal pyramidal neurons. We then show that the probability of feed-forward connections from corticocortical neurons to corticotectal neurons is approximately three- to fourfold higher than the probability of monosynaptic connections among corticocortical or corticotectal cells. Moreover, we found that the average axodendritic overlap of the presynaptic and postsynaptic pyramidal neurons could not fully explain the differences in connection probability that we observed. The selective synaptic interactions we describe demonstrate that the organization of local networks of pyramidal cells reflects the long-range targets of both the presynaptic and postsynaptic neurons.

Multidisciplinary, Multidisciplinaire, Sciences biologiques et medicales, Biological and medical sciences, Sciences biologiques fondamentales et appliquees. Psychologie, Fundamental and applied biological sciences. Psychology, Vertebres: systeme nerveux et organes des sens, Vertebrates: nervous system and sense organs, Système nerveux central, Central nervous system, Sistema nervioso central, Bruit, Noise, Ruido, Cognition, Cognición, Encéphale, Encephalon, Encéfalo, Homme, Human, Hombre, Modèle, Models, Modelo, Neurone sensoriel, Sensory neuron, Neurona sensorial, Récompense, Reward, Recompensa, Stimulus, and Estímulo

During perceptual decisions, the activity of sensory neurons correlates with a subject's percept, even when the physical stimulus is identical1-9. The origin of this correlation is unknown. Current theory proposes a causal effect of noise in sensory neurons on perceptual decisions10-12, but the correlation could result from different brain states associated with the perceptual choice13 (a top-down explanation). These two schemes have very different implications for the role of sensory neurons in forming decisions14. Here we use white-noise analysis15 to measure tuning functions of V2 neurons associated with choice and simultaneously measure how the variation in the stimulus affects the subjects' (two macaques) perceptual decisions16-18. In causal models, stronger effects of the stimulus upon decisions, mediated by sensory neurons, are associated with stronger choice-related activity. However, we find that over the time course of the trial these measures change in different directions-at odds with causal models. An analysis of the effect of reward size also supports this conclusion. Finally, we find that choice is associated with changes in neuronal gain that are incompatible with causal models. All three results are readily explained if choice is associated with changes in neuronal gain caused by top-down phenomena that closely resemble attention19. We conclude that top-down processes contribute to choice-related activity. Thus, even forming simple sensory decisions involves complex interactions between cognitive processes and sensory neurons.