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1.
Cell ; 184(18): 4819-4837.e22, 2021 09 02.
Artículo en Inglés | MEDLINE | ID: mdl-34380046

RESUMEN

Animal bodies are composed of cell types with unique expression programs that implement their distinct locations, shapes, structures, and functions. Based on these properties, cell types assemble into specific tissues and organs. To systematically explore the link between cell-type-specific gene expression and morphology, we registered an expression atlas to a whole-body electron microscopy volume of the nereid Platynereis dumerilii. Automated segmentation of cells and nuclei identifies major cell classes and establishes a link between gene activation, chromatin topography, and nuclear size. Clustering of segmented cells according to gene expression reveals spatially coherent tissues. In the brain, genetically defined groups of neurons match ganglionic nuclei with coherent projections. Besides interneurons, we uncover sensory-neurosecretory cells in the nereid mushroom bodies, which thus qualify as sensory organs. They furthermore resemble the vertebrate telencephalon by molecular anatomy. We provide an integrated browser as a Fiji plugin for remote exploration of all available multimodal datasets.


Asunto(s)
Forma de la Célula , Regulación de la Expresión Génica , Poliquetos/citología , Poliquetos/genética , Análisis de la Célula Individual , Animales , Núcleo Celular/metabolismo , Ganglios de Invertebrados/metabolismo , Perfilación de la Expresión Génica , Familia de Multigenes , Imagen Multimodal , Cuerpos Pedunculados/metabolismo , Poliquetos/ultraestructura
2.
Annu Rev Neurosci ; 44: 275-293, 2021 07 08.
Artículo en Inglés | MEDLINE | ID: mdl-33730512

RESUMEN

The dense reconstruction of neuronal wiring diagrams from volumetric electron microscopy data has the potential to generate fundamentally new insights into mechanisms of information processing and storage in neuronal circuits. Zebrafish provide unique opportunities for dynamical connectomics approaches that combine reconstructions of wiring diagrams with measurements of neuronal population activity and behavior. Such approaches have the power to reveal higher-order structure in wiring diagrams that cannot be detected by sparse sampling of connectivity and that is essential for neuronal computations. In the brain stem, recurrently connected neuronal modules were identified that can account for slow, low-dimensional dynamics in an integrator circuit. In the spinal cord, connectivity specifies functional differences between premotor interneurons. In the olfactory bulb, tuning-dependent connectivity implements a whitening transformation that is based on the selective suppression of responses to overrepresented stimulus features. These findings illustrate the potential of dynamical connectomics in zebrafish to analyze the circuit mechanisms underlying higher-order neuronal computations.


Asunto(s)
Red Nerviosa , Pez Cebra , Animales , Interneuronas , Neuronas , Bulbo Olfatorio
3.
Nat Methods ; 17(3): 343-351, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-32123394

RESUMEN

Virtual realities are powerful tools to analyze and manipulate interactions between animals and their environment and to enable measurements of neuronal activity during behavior. In many species, however, optical access to the brain and/or the behavioral repertoire are limited. We developed a high-resolution virtual reality for head-restrained adult zebrafish, which exhibit cognitive behaviors not shown by larvae. We noninvasively measured activity throughout the dorsal telencephalon by multiphoton calcium imaging. Fish in the virtual reality showed regular swimming patterns and were attracted to animations of conspecifics. Manipulations of visuo-motor feedback revealed neurons that responded selectively to the mismatch between the expected and the actual visual consequences of motor output. Such error signals were prominent in multiple telencephalic areas, consistent with models of predictive processing. A virtual reality system for adult zebrafish therefore provides opportunities to analyze neuronal processing mechanisms underlying higher brain functions including decision making, associative learning, and social interactions.


Asunto(s)
Conducta Animal , Encéfalo/diagnóstico por imagen , Neuronas/fisiología , Interfaz Usuario-Computador , Realidad Virtual , Animales , Mapeo Encefálico , Cognición , Toma de Decisiones , Femenino , Masculino , Destreza Motora , Probabilidad , Conducta Social , Natación , Pez Cebra
4.
Annu Rev Neurosci ; 36: 383-402, 2013 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-23725002

RESUMEN

The main olfactory system encodes information about molecules in a combinatorial fashion by distributed spatiotemporal activity patterns. As activity propagates from sensory neurons to the olfactory bulb and to higher brain areas, odor information is processed by multiple transformations of these activity patterns. This review discusses neuronal computations associated with such transformations in the olfactory system of zebrafish, a small vertebrate that offers advantages for the quantitative analysis and manipulation of neuronal activity in the intact brain. The review focuses on pattern decorrelation in the olfactory bulb and on the readout of multiplexed sensory representations in the telencephalic area Dp, the homolog of the olfactory cortex. These computations are difficult to study in larger species and may provide insights into general information-processing strategies in the brain.


Asunto(s)
Simulación por Computador , Modelos Neurológicos , Neuronas/fisiología , Vías Olfatorias/citología , Animales , Pez Cebra/anatomía & histología
5.
Nature ; 509(7501): 453-8, 2014 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-24814341

RESUMEN

Learning is mediated by experience-dependent plasticity in neuronal circuits. Activity in neuronal circuits is tightly regulated by different subtypes of inhibitory interneurons, yet their role in learning is poorly understood. Using a combination of in vivo single-unit recordings and optogenetic manipulations, we show that in the mouse basolateral amygdala, interneurons expressing parvalbumin (PV) and somatostatin (SOM) bidirectionally control the acquisition of fear conditioning--a simple form of associative learning--through two distinct disinhibitory mechanisms. During an auditory cue, PV(+) interneurons are excited and indirectly disinhibit the dendrites of basolateral amygdala principal neurons via SOM(+) interneurons, thereby enhancing auditory responses and promoting cue-shock associations. During an aversive footshock, however, both PV(+) and SOM(+) interneurons are inhibited, which boosts postsynaptic footshock responses and gates learning. These results demonstrate that associative learning is dynamically regulated by the stimulus-specific activation of distinct disinhibitory microcircuits through precise interactions between different subtypes of local interneurons.


Asunto(s)
Amígdala del Cerebelo/citología , Amígdala del Cerebelo/fisiología , Miedo/fisiología , Inhibición Psicológica , Interneuronas/metabolismo , Aprendizaje/fisiología , Animales , Condicionamiento Clásico , Electrochoque , Miembro Posterior , Masculino , Ratones , Optogenética , Parvalbúminas/metabolismo , Somatostatina/metabolismo , Sinapsis/metabolismo
6.
PLoS Comput Biol ; 14(5): e1006157, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29782491

RESUMEN

In recent years, two-photon calcium imaging has become a standard tool to probe the function of neural circuits and to study computations in neuronal populations. However, the acquired signal is only an indirect measurement of neural activity due to the comparatively slow dynamics of fluorescent calcium indicators. Different algorithms for estimating spike rates from noisy calcium measurements have been proposed in the past, but it is an open question how far performance can be improved. Here, we report the results of the spikefinder challenge, launched to catalyze the development of new spike rate inference algorithms through crowd-sourcing. We present ten of the submitted algorithms which show improved performance compared to previously evaluated methods. Interestingly, the top-performing algorithms are based on a wide range of principles from deep neural networks to generative models, yet provide highly correlated estimates of the neural activity. The competition shows that benchmark challenges can drive algorithmic developments in neuroscience.


Asunto(s)
Potenciales de Acción/fisiología , Calcio/metabolismo , Biología Computacional/métodos , Modelos Neurológicos , Algoritmos , Animales , Calcio/química , Calcio/fisiología , Bases de Datos Factuales , Ratones , Imagen Molecular , Imagen Óptica , Retina/citología , Neuronas Retinianas/citología , Neuronas Retinianas/metabolismo
7.
Exp Brain Res ; 236(11): 2959-2969, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30088022

RESUMEN

The zebrafish is a model organism to study olfactory information processing, but efficient behavioral procedures to analyze olfactory discrimination and memory are lacking. We devised an automated odor discrimination task for adult zebrafish based on olfactory conditioning of feeding behavior. Presentation of a conditioned odor (CS+), but not a neutral odor (CS-) was followed by food delivery at a specific location. Fish developed differential behavioral responses to CS+ and CS- within a few trials. The behavioral response to the CS+ was complex and included components reminiscent of food search such as increased swimming speed and water surface sampling. Appetitive behavior was therefore quantified by a composite score that combined measurements of multiple behavioral parameters. Robust discrimination behavior was observed in different strains, even when odors were chemically similar, and learned preferences could overcome innate odor preferences. These results confirm that zebrafish can rapidly learn to make fine odor discriminations. The procedure is efficient and provides novel opportunities to dissect the neural mechanisms underlying olfactory discrimination and memory.


Asunto(s)
Condicionamiento Clásico/fisiología , Aprendizaje Discriminativo/fisiología , Percepción Olfatoria/fisiología , Olfato/fisiología , Animales , Conducta Alimentaria/fisiología , Femenino , Masculino , Odorantes , Pez Cebra
8.
Nature ; 479(7374): 493-8, 2011 Nov 13.
Artículo en Inglés | MEDLINE | ID: mdl-22080956

RESUMEN

Neuronal activity patterns contain information in their temporal structure, indicating that information transfer between neurons may be optimized by temporal filtering. In the zebrafish olfactory bulb, subsets of output neurons (mitral cells) engage in synchronized oscillations during odour responses, but information about odour identity is contained mostly in non-oscillatory firing rate patterns. Using optogenetic manipulations and odour stimulation, we found that firing rate responses of neurons in the posterior zone of the dorsal telencephalon (Dp), a target area homologous to olfactory cortex, were largely insensitive to oscillatory synchrony of mitral cells because passive membrane properties and synaptic currents act as low-pass filters. Nevertheless, synchrony influenced spike timing. Moreover, Dp neurons responded primarily during the decorrelated steady state of mitral cell activity patterns. Temporal filtering therefore tunes Dp neurons to components of mitral cell activity patterns that are particularly informative about precise odour identity. These results demonstrate how temporal filtering can extract specific information from multiplexed neuronal codes.


Asunto(s)
Modelos Neurológicos , Neuronas/fisiología , Odorantes/análisis , Bulbo Olfatorio/citología , Bulbo Olfatorio/fisiología , Pez Cebra/fisiología , Potenciales de Acción , Animales , Vías Olfatorias/fisiología , Estimulación Luminosa , Estimulación Física , Factores de Tiempo
10.
Nature ; 465(7294): 47-52, 2010 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-20393466

RESUMEN

The categorial nature of sensory, cognitive and behavioural acts indicates that the brain classifies neuronal activity patterns into discrete representations. Pattern classification may be achieved by abrupt switching between discrete activity states of neuronal circuits, but few experimental studies have directly tested this. We gradually varied the concentration or molecular identity of odours and optically measured responses across output neurons of the olfactory bulb in zebrafish. Whereas population activity patterns were largely insensitive to changes in odour concentration, morphing of one odour into another resulted in abrupt transitions between odour representations. These transitions were mediated by coordinated response changes among small neuronal ensembles rather than by shifts in the global network state. The olfactory bulb therefore classifies odour-evoked input patterns into many discrete and defined output patterns, as proposed by attractor models. This computation is consistent with perceptual phenomena and may represent a general information processing strategy in the brain.


Asunto(s)
Red Nerviosa/fisiología , Bulbo Olfatorio/fisiología , Sensación/fisiología , Pez Cebra/fisiología , Animales , Odorantes
11.
Curr Biol ; 34(2): 298-312.e4, 2024 01 22.
Artículo en Inglés | MEDLINE | ID: mdl-38157860

RESUMEN

The function of neuronal networks is determined not only by synaptic connectivity but also by neuromodulatory systems that broadcast information via distributed connections and volume transmission. To understand the molecular constraints that organize neuromodulatory signaling in the telencephalon of adult zebrafish, we used transcriptomics and additional approaches to delineate cell types, to determine their phylogenetic conservation, and to map the expression of marker genes at high granularity. The combinatorial expression of GPCRs and cell-type markers indicates that all neuronal cell types are subject to modulation by multiple monoaminergic systems and distinct combinations of neuropeptides. Individual cell types were associated with multiple (typically >30) neuromodulatory signaling networks but expressed only a few diagnostic GPCRs at high levels, suggesting that different neuromodulatory systems act in combination, albeit with unequal weights. These results provide a detailed map of cell types and brain areas in the zebrafish telencephalon, identify core components of neuromodulatory networks, highlight the cell-type specificity of neuropeptides and GPCRs, and begin to decipher the logic of combinatorial neuromodulation.


Asunto(s)
Neuropéptidos , Pez Cebra , Animales , Pez Cebra/fisiología , Filogenia , Neuronas/metabolismo , Telencéfalo , Neuropéptidos/metabolismo
12.
J Neurosci ; 32(20): 6830-40, 2012 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-22593052

RESUMEN

In the olfactory bulb, the modulatory neurotransmitter dopamine (DA) is coexpressed with GABA by local interneurons, but its role in odor processing remains obscure. We examined functions of DA mediated by D2-like receptors in the olfactory bulb of adult zebrafish by pharmacology, whole-cell recordings, calcium imaging, and optogenetics. Bath application of DA had no detectable effect on odorant-evoked sensory input. DA directly hyperpolarized mitral cells (MCs) via D2-like receptors and slightly increased their response gain. Consistent with this effect on input-output functions of MCs, small odorant responses were suppressed, whereas strong responses were enhanced in the presence of DA. These effects increased the root-mean-square contrast of population activity patterns but did not reduce their correlations. Optical stimulation of interneurons expressing channelrhodopsin-2 evoked fast GABAergic inhibitory currents in mitral cells but failed to activate D2 receptor-mediated currents when stimuli were short. Prolonged stimulus trains, however, activated a slow hyperpolarizing current that was blocked by an antagonist of D2-like receptors. GABA and DA are therefore both released from interneurons by electrical activity and hyperpolarize MCs, but D2-dependent dopaminergic effects occur on slower timescales. Additional effects of DA may be mediated by D1-like receptors. These results indicate that DA acts on D2-like receptors via asynchronous release and/or volume transmission and implicate DA in the slow adaptation of circuit function. The shift of the membrane potential away from spike threshold could adapt mitral cells to background input without compromising their sensitivity.


Asunto(s)
Dopamina/fisiología , Bulbo Olfatorio/fisiología , Percepción Olfatoria/fisiología , Neuronas Receptoras Olfatorias/fisiología , Receptores de Dopamina D2/fisiología , Animales , Animales Modificados Genéticamente , Dopamina/farmacología , Antagonistas de los Receptores de Dopamina D2 , Técnicas In Vitro , Interneuronas/fisiología , Potenciales de la Membrana/efectos de los fármacos , Potenciales de la Membrana/fisiología , Modelos Neurológicos , Imagen Molecular/métodos , Bulbo Olfatorio/efectos de los fármacos , Técnicas de Placa-Clamp/métodos , Estimulación Luminosa/métodos , Rodopsina/genética , Rodopsina/metabolismo , Estimulación Química , Factores de Tiempo , Pez Cebra
13.
J Neurosci ; 32(41): 14102-8, 2012 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-23055479

RESUMEN

The olfactory system encodes information about molecules by spatiotemporal patterns of activity across distributed populations of neurons and extracts information from these patterns to control specific behaviors. Recent studies used in vivo recordings, optogenetics, and other methods to analyze the mechanisms by which odor information is encoded and processed in the olfactory system, the functional connectivity within and between olfactory brain areas, and the impact of spatiotemporal patterning of neuronal activity on higher-order neurons and behavioral outputs. The results give rise to a faceted picture of olfactory processing and provide insights into fundamental mechanisms underlying neuronal computations. This review focuses on some of this work presented in a Mini-Symposium at the Annual Meeting of the Society for Neuroscience in 2012.


Asunto(s)
Odorantes , Bulbo Olfatorio/fisiología , Vías Olfatorias/fisiología , Neuronas Receptoras Olfatorias/fisiología , Optogenética , Animales , Humanos , Bulbo Olfatorio/química , Vías Olfatorias/química , Neuronas Receptoras Olfatorias/química , Optogenética/métodos
14.
Elife ; 112022 07 22.
Artículo en Inglés | MEDLINE | ID: mdl-35866706

RESUMEN

The zebrafish is an important model in systems neuroscience but viral tools to dissect the structure and function of neuronal circuitry are not established. We developed methods for efficient gene transfer and retrograde tracing in adult and larval zebrafish by herpes simplex viruses (HSV1). HSV1 was combined with the Gal4/UAS system to target cell types with high spatial, temporal, and molecular specificity. We also established methods for efficient transneuronal tracing by modified rabies viruses in zebrafish. We demonstrate that HSV1 and rabies viruses can be used to visualize and manipulate genetically or anatomically identified neurons within and across different brain areas of adult and larval zebrafish. An expandable library of viruses is provided to express fluorescent proteins, calcium indicators, optogenetic probes, toxins and other molecular tools. This toolbox creates new opportunities to interrogate neuronal circuits in zebrafish through combinations of genetic and viral approaches.


Asunto(s)
Virus de la Rabia , Pez Cebra , Animales , Expresión Génica , Neuronas/fisiología , Optogenética/métodos , Virus de la Rabia/genética , Pez Cebra/genética
15.
Neuron ; 109(10): 1590-1592, 2021 05 19.
Artículo en Inglés | MEDLINE | ID: mdl-34015265

RESUMEN

In this issue of Neuron, Gurnani and Silver (2021) report that activity across Golgi cells, a major type of inhibitory interneuron in the cerebellar cortex, is multidimensional and modulated by behavior. These results suggest multiple functions for inhibition in cerebellar computations.


Asunto(s)
Corteza Cerebelosa , Interneuronas , Cerebelo , Neuronas
16.
Nat Neurosci ; 24(9): 1324-1337, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34341584

RESUMEN

Inference of action potentials ('spikes') from neuronal calcium signals is complicated by the scarcity of simultaneous measurements of action potentials and calcium signals ('ground truth'). In this study, we compiled a large, diverse ground truth database from publicly available and newly performed recordings in zebrafish and mice covering a broad range of calcium indicators, cell types and signal-to-noise ratios, comprising a total of more than 35 recording hours from 298 neurons. We developed an algorithm for spike inference (termed CASCADE) that is based on supervised deep networks, takes advantage of the ground truth database, infers absolute spike rates and outperforms existing model-based algorithms. To optimize performance for unseen imaging data, CASCADE retrains itself by resampling ground truth data to match the respective sampling rate and noise level; therefore, no parameters need to be adjusted by the user. In addition, we developed systematic performance assessments for unseen data, openly released a resource toolbox and provide a user-friendly cloud-based implementation.


Asunto(s)
Artefactos , Encéfalo/fisiología , Aprendizaje Profundo , Neuroimagen/métodos , Neuronas/fisiología , Potenciales de Acción/fisiología , Animales , Calcio/metabolismo , Bases de Datos Factuales , Ratones , Modelos Neurológicos , Pez Cebra
18.
J Comput Neurosci ; 28(1): 29-45, 2010 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19714457

RESUMEN

The early processing of sensory information by neuronal circuits often includes a reshaping of activity patterns that may facilitate further processing in the brain. For instance, in the olfactory system the activity patterns that related odors evoke at the input of the olfactory bulb can be highly similar. Nevertheless, the corresponding activity patterns of the mitral cells, which represent the output of the olfactory bulb, can differ significantly from each other due to strong inhibition by granule cells and peri-glomerular cells. Motivated by these results we study simple adaptive inhibitory networks that aim to separate or even orthogonalize activity patterns representing similar stimuli. Since the animal experiences the different stimuli at different times it is difficult for the network to learn the connectivity based on their similarity; biologically it is more plausible that learning is driven by simultaneous correlations between the input channels. We investigate the connection between pattern orthogonalization and channel decorrelation and demonstrate that networks can achieve effective pattern orthogonalization through channel decorrelation if they simultaneously equalize their output levels. In feedforward networks biophysically plausible learning mechanisms fail, however, for even moderately similar input patterns. Recurrent networks do not have that limitation; they can orthogonalize the representations of highly similar input patterns. Even when they are optimized for linear neuronal dynamics they perform very well when the dynamics are nonlinear. These results provide insights into fundamental features of simplified inhibitory networks that may be relevant for pattern orthogonalization by neuronal circuits in general.


Asunto(s)
Inhibición Neural/fisiología , Redes Neurales de la Computación , Neuronas/fisiología , Transmisión Sináptica/fisiología , Algoritmos , Animales , Modelos Lineales , Vías Nerviosas/fisiología , Dinámicas no Lineales , Bulbo Olfatorio/fisiología , Percepción Olfatoria/fisiología
19.
PLoS Biol ; 5(7): e178, 2007 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-17608564

RESUMEN

Odors are initially represented in the olfactory bulb (OB) by patterns of sensory input across the array of glomeruli. Although activated glomeruli are often widely distributed, glomeruli responding to stimuli sharing molecular features tend to be loosely clustered and thus establish a fractured chemotopic map. Neuronal circuits in the OB transform glomerular patterns of sensory input into spatiotemporal patterns of output activity and thereby extract information about a stimulus. It is, however, unknown whether the chemotopic spatial organization of glomerular inputs is maintained during these computations. To explore this issue, we measured spatiotemporal patterns of odor-evoked activity across thousands of individual neurons in the zebrafish OB by temporally deconvolved two-photon Ca(2+) imaging. Mitral cells and interneurons were distinguished by transgenic markers and exhibited different response selectivities. Shortly after response onset, activity patterns exhibited foci of activity associated with certain chemical features throughout all layers. During the subsequent few hundred milliseconds, however, MC activity was locally sparsened within the initial foci in an odor-specific manner. As a consequence, chemotopic maps disappeared and activity patterns became more informative about precise odor identity. Hence, chemotopic maps of glomerular input activity are initially transmitted to OB outputs, but not maintained during pattern processing. Nevertheless, transient chemotopic maps may support neuronal computations by establishing important synaptic interactions within the circuit. These results provide insights into the functional topology of neural activity patterns and its potential role in circuit function.


Asunto(s)
Bulbo Olfatorio/anatomía & histología , Bulbo Olfatorio/fisiología , Pez Cebra/anatomía & histología , Pez Cebra/fisiología , Animales , Animales Modificados Genéticamente , Señalización del Calcio , Potenciales Evocados , Retroalimentación Fisiológica , Interneuronas/fisiología , Proteínas Luminiscentes/genética , Odorantes , Vías Olfatorias/fisiología , Proteínas Recombinantes/genética , Pez Cebra/genética
20.
Nat Neurosci ; 23(3): 433-442, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31959937

RESUMEN

Neuronal computations underlying higher brain functions depend on synaptic interactions among specific neurons. A mechanistic understanding of such computations requires wiring diagrams of neuronal networks. In this study, we examined how the olfactory bulb (OB) performs 'whitening', a fundamental computation that decorrelates activity patterns and supports their classification by memory networks. We measured odor-evoked activity in the OB of a zebrafish larva and subsequently reconstructed the complete wiring diagram by volumetric electron microscopy. The resulting functional connectome revealed an over-representation of multisynaptic connectivity motifs that mediate reciprocal inhibition between neurons with similar tuning. This connectivity suppressed redundant responses and was necessary and sufficient to reproduce whitening in simulations. Whitening of odor representations is therefore mediated by higher-order structure in the wiring diagram that is adapted to natural input patterns.


Asunto(s)
Odorantes , Bulbo Olfatorio/fisiología , Algoritmos , Animales , Conectoma , Fenómenos Electrofisiológicos/fisiología , Larva , Memoria/fisiología , Modelos Neurológicos , Red Nerviosa/anatomía & histología , Red Nerviosa/fisiología , Vías Olfatorias/fisiología , Percepción Olfatoria , Sinapsis/fisiología , Pez Cebra
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