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1.
Nat Methods ; 17(1): 107-113, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31686040

RESUMEN

Spontaneous and sensory-evoked activity propagates across varying spatial scales in the mammalian cortex, but technical challenges have limited conceptual links between the function of local neuronal circuits and brain-wide network dynamics. We present a method for simultaneous cellular-resolution two-photon calcium imaging of a local microcircuit and mesoscopic widefield calcium imaging of the entire cortical mantle in awake mice. Our multi-scale approach involves a microscope with an orthogonal axis design where the mesoscopic objective is oriented above the brain and the two-photon objective is oriented horizontally, with imaging performed through a microprism. We also introduce a viral transduction method for robust and widespread gene delivery in the mouse brain. These approaches allow us to identify the behavioral state-dependent functional connectivity of pyramidal neurons and vasoactive intestinal peptide-expressing interneurons with long-range cortical networks. Our imaging system provides a powerful strategy for investigating cortical architecture across a wide range of spatial scales.


Asunto(s)
Encéfalo/fisiología , Calcio/metabolismo , Corteza Cerebral/fisiología , Red Nerviosa/fisiología , Neuroimagen/métodos , Neuronas/fisiología , Fotones , Animales , Conducta Animal , Encéfalo/citología , Corteza Cerebral/citología , Interneuronas/citología , Interneuronas/fisiología , Ratones , Neuronas/citología , Células Piramidales/citología , Células Piramidales/fisiología , Péptido Intestinal Vasoactivo/metabolismo
2.
Science ; 385(6710): eadh7814, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39146415

RESUMEN

Spontaneous activity refines neural connectivity prior to the onset of sensory experience, but it remains unclear how such activity instructs axonal connectivity with subcellular precision. We simultaneously measured spontaneous retinal waves and the activity of individual retinocollicular axons and tracked morphological changes in axonal arbors across hours in vivo in neonatal mice. We demonstrate that the correlation of an axon branch's activity with neighboring axons or postsynaptic neurons predicts whether the branch will be added, stabilized, or eliminated. Desynchronizing individual axons from their local networks, changing the pattern of correlated activity, or blocking N-methyl-d-aspartate receptors all significantly altered single-axon morphology. These observations provide the first direct evidence in vivo that endogenous patterns of correlated neuronal activity instruct fine-scale refinement of axonal processes.


Asunto(s)
Axones , Receptores de N-Metil-D-Aspartato , Células Ganglionares de la Retina , Animales , Ratones , Axones/fisiología , Receptores de N-Metil-D-Aspartato/metabolismo , Células Ganglionares de la Retina/fisiología , Colículos Superiores/fisiología , Plasticidad Neuronal , Ratones Mutantes
3.
Nat Neurosci ; 27(1): 148-158, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38036743

RESUMEN

Experimental work across species has demonstrated that spontaneously generated behaviors are robustly coupled to variations in neural activity within the cerebral cortex. Functional magnetic resonance imaging data suggest that temporal correlations in cortical networks vary across distinct behavioral states, providing for the dynamic reorganization of patterned activity. However, these data generally lack the temporal resolution to establish links between cortical signals and the continuously varying fluctuations in spontaneous behavior observed in awake animals. Here, we used wide-field mesoscopic calcium imaging to monitor cortical dynamics in awake mice and developed an approach to quantify rapidly time-varying functional connectivity. We show that spontaneous behaviors are represented by fast changes in both the magnitude and correlational structure of cortical network activity. Combining mesoscopic imaging with simultaneous cellular-resolution two-photon microscopy demonstrated that correlations among neighboring neurons and between local and large-scale networks also encode behavior. Finally, the dynamic functional connectivity of mesoscale signals revealed subnetworks not predicted by traditional anatomical atlas-based parcellation of the cortex. These results provide new insights into how behavioral information is represented across the neocortex and demonstrate an analytical framework for investigating time-varying functional connectivity in neural networks.


Asunto(s)
Neocórtex , Neuronas , Ratones , Animales , Neuronas/fisiología , Imagen por Resonancia Magnética , Vigilia , Neocórtex/diagnóstico por imagen , Mapeo Encefálico/métodos , Vías Nerviosas/fisiología
4.
Trends Neurosci ; 46(7): 508-524, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37164869

RESUMEN

The rapid and coordinated propagation of neural activity across the brain provides the foundation for complex behavior and cognition. Technical advances across neuroscience subfields have advanced understanding of these dynamics, but points of convergence are often obscured by semantic differences, creating silos of subfield-specific findings. In this review we describe how a parsimonious conceptualization of brain state as the fundamental building block of whole-brain activity offers a common framework to relate findings across scales and species. We present examples of the diverse techniques commonly used to study brain states associated with physiology and higher-order cognitive processes, and discuss how integration across them will enable a more comprehensive and mechanistic characterization of the neural dynamics that are crucial to survival but are disrupted in disease.


Asunto(s)
Encéfalo , Neurociencias , Humanos , Encéfalo/fisiología , Cognición/fisiología
5.
Nat Commun ; 12(1): 2449, 2021 04 27.
Artículo en Inglés | MEDLINE | ID: mdl-33907194

RESUMEN

In the developing auditory system, spontaneous activity generated in the cochleae propagates into the central nervous system to promote circuit formation. The effects of peripheral firing patterns on spontaneous activity in the central auditory system are not well understood. Here, we describe wide-spread bilateral coupling of spontaneous activity that coincides with the period of transient efferent modulation of inner hair cells from the brainstem medial olivocochlear system. Knocking out α9/α10 nicotinic acetylcholine receptors, a requisite part of the efferent pathway, profoundly reduces bilateral correlations. Pharmacological and chemogenetic experiments confirm that the efferent system is necessary for normal bilateral coupling. Moreover, auditory sensitivity at hearing onset is reduced in the absence of pre-hearing efferent modulation. Together, these results demonstrate how afferent and efferent pathways collectively shape spontaneous activity patterns and reveal the important role of efferents in coordinating bilateral spontaneous activity and the emergence of functional responses during the prehearing period.


Asunto(s)
Vías Auditivas/fisiología , Cóclea/fisiología , Vías Eferentes/fisiología , Retroalimentación Fisiológica , Receptores Nicotínicos/genética , Estimulación Acústica , Animales , Vías Auditivas/citología , Cóclea/citología , Lateralidad Funcional/fisiología , Expresión Génica , Células Ciliadas Auditivas Internas/citología , Células Ciliadas Auditivas Internas/fisiología , Colículos Inferiores/citología , Colículos Inferiores/fisiología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Núcleo Olivar/citología , Núcleo Olivar/fisiología , Receptores Nicotínicos/deficiencia
6.
Nat Commun ; 5: 4294, 2014 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-25014177

RESUMEN

The role of remote astrocyte (AC) reaction to central or peripheral axonal insult is not clearly understood. Here we use a transgenic approach to compare the direct influence of normal with diminished AC reactivity on neuronal integrity and synapse recovery following extracranial facial nerve transection in mice. Our model allows straightforward interpretations of AC-neuron signalling by reducing confounding effects imposed by inflammatory cells. We show direct evidence that perineuronal reactive ACs play a major role in maintaining neuronal circuitry following distant axotomy. We reveal a novel function of astrocytic signal transducer and activator of transcription-3 (STAT3). STAT3 regulates perineuronal astrocytic process formation and re-expression of a synaptogenic molecule, thrombospondin-1 (TSP-1), apart from supporting neuronal integrity. We demonstrate that, through this new pathway, TSP-1 is responsible for the remote AC-mediated recovery of excitatory synapses onto axotomized motor neurons in adult mice. These data provide new targets for neuroprotective therapies via optimizing AC-driven plasticity.


Asunto(s)
Astrocitos/fisiología , Neuronas Motoras/fisiología , Plasticidad Neuronal/fisiología , Factor de Transcripción STAT3/fisiología , Transducción de Señal/fisiología , Sinapsis/fisiología , Trombospondina 1/fisiología , Animales , Astrocitos/citología , Axotomía , Células Cultivadas , Traumatismos del Nervio Facial/fisiopatología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Modelos Animales , Regeneración Nerviosa/fisiología , Técnicas de Placa-Clamp , Factor de Transcripción STAT3/deficiencia , Factor de Transcripción STAT3/genética , Trombospondina 1/deficiencia , Trombospondina 1/genética
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