Modular output circuits of the fastigial nucleus for diverse motor and nonmotor functions of the cerebellar vermis

eLife, Journal Year: 2020, Volume and Issue: 9

Published: July 8, 2020

The cerebellar vermis, long associated with axial motor control, has been implicated in a surprising range of neuropsychiatric disorders and cognitive affective functions. Remarkably little is known, however, about the specific cell types neural circuits responsible for these diverse Here, using single-cell gene expression profiling anatomical circuit analyses vermis output neurons mouse fastigial (medial cerebellar) nucleus, we identify five major classes glutamatergic projection distinguished by expression, morphology, distribution, input-output connectivity. Each type connected set Purkinje cells inferior olive turn innervates distinct collection downstream targets. Transsynaptic tracing indicates extensive disynaptic links cognitive, affective, forebrain circuits. These results indicate that functions could be mediated modular synaptic connections posturomotor, oromotor, positional-autonomic, orienting, vigilance

Language: Английский

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The mouse cortico–basal ganglia–thalamic network

Nature, Journal Year: 2021, Volume and Issue: 598(7879), P. 188 - 194

Published: Oct. 6, 2021

The cortico-basal ganglia-thalamo-cortical loop is one of the fundamental network motifs in brain. Revealing its structural and functional organization critical to understanding cognition, sensorimotor behaviour, natural history many neurological neuropsychiatric disorders. Classically, this conceptualized contain three information channels: motor, limbic associative1-4. Yet three-channel view cannot explain myriad functions basal ganglia. We previously subdivided dorsal striatum into 29 domains on basis topography inputs from entire cortex5. Here we map multi-synaptic output pathways these striatal through globus pallidus external part (GPe), substantia nigra reticular (SNr), thalamic nuclei cortex. Accordingly, identify 14 SNr 36 GPe a direct cortico-SNr projection. striatonigral pathway displays greater convergence than more parallel striatopallidal indirect pathway, although originating same domain ultimately converge onto postsynaptic neurons. Following outputs, delineate six parafascicular ventromedial nuclei. Subsequently, ganglia-thalamic subnetworks that sequentially transduce specific subsets cortical every elemental node cortico-basal loop. Thalamic relay back corticostriatal neurons each subnetwork bona fide closed

Language: Английский

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Adeno-Associated Virus Technologies and Methods for Targeted Neuronal Manipulation

Frontiers in Neuroanatomy, Journal Year: 2019, Volume and Issue: 13

Published: Nov. 26, 2019

Cell-type-specific expression of molecular tools and sensors is critical to construct circuit diagrams investigate the activity function neurons within nervous system. Strategies for targeted manipulation include combinations classical genetic such as Cre/loxP Flp/FRT, use cis-regulatory elements, knock-in transgenic mice, gene delivery by AAV other viral vectors. The combination these complex technologies with goal precise neuronal targeting a challenge in lab. This report will discuss theoretical practical aspects combining current establish best practices achieving specific cell types. Novel applications tools, well areas development, be envisioned discussed.

Language: Английский

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Anatomically segregated basal ganglia pathways allow parallel behavioral modulation

Nature Neuroscience, Journal Year: 2020, Volume and Issue: 23(11), P. 1388 - 1398

Published: Sept. 28, 2020

Language: Английский

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The cerebellum directly modulates the substantia nigra dopaminergic activity

Nature Neuroscience, Journal Year: 2024, Volume and Issue: 27(3), P. 497 - 513

Published: Jan. 25, 2024

Language: Английский

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Basal ganglia–spinal cord pathway that commands locomotor gait asymmetries in mice

Nature Neuroscience, Journal Year: 2024, Volume and Issue: 27(4), P. 716 - 727

Published: Feb. 12, 2024

Abstract The basal ganglia are essential for executing motor actions. How the engage spinal networks has remained elusive. Medullary Chx10 gigantocellular (Gi) neurons required turning gait programs, suggesting that gaits organized by executed via this descending pathway. Performing deep brainstem recordings of Gi Ca 2+ activity in adult mice, we show striatal projection initiate a dominant crossed pathway to on contralateral side. Using intersectional viral tracing and cell-type-specific modulation, uncover principal ganglia–spinal cord locomotor asymmetries mice: → pontine reticular nucleus, oral part (PnO) cord. Modulating restricted PnO restores competence upon damage, dysfunction may contribute debilitating deficits observed Parkinson’s disease. Our results reveal stratified circuit architecture underlying critical program.

Language: Английский

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Persistent enhancement of basolateral amygdala-dorsomedial striatum synapses causes compulsive-like behaviors in mice

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 8, 2024

Abstract Compulsive behaviors are observed in a range of psychiatric disorders, however the neural substrates underlying not clearly defined. Here we show that basolateral amygdala-dorsomedial striatum (BLA-DMS) circuit activation leads to manifestation compulsive-like behaviors. We revealed BLA neurons projecting DMS, mainly onto dopamine D1 receptor-expressing neurons, largely overlap with neuronal population responds aversive predator stress, widely used anxiogenic stressor. Specific optogenetic BLA-DMS induced strong anxiety response followed by compulsive grooming. Furthermore, developed mouse model for compulsivity displaying wide spectrum chronically activating circuit. In these mice, persistent molecular changes at synapses were causally related phenotypes. Together, our study demonstrates involvement emergence enduring via its synaptic changes.

Language: Английский

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Reviving-like prosocial behavior in response to unconscious or dead conspecifics in rodents

Science, Journal Year: 2025, Volume and Issue: 387(6736)

Published: Feb. 20, 2025

Whereas humans exhibit emergency responses to assist unconscious individuals, how nonhuman animals react unresponsive conspecifics is less well understood. We report that mice stereotypic behaviors toward or dead social partners, which escalate from sniffing and grooming more forceful actions such as mouth tongue biting pulling. The latter intense actions, prominent in familiar pairs, begin after prolonged immobility unresponsiveness cease when the partner regains activity. Their consequences, including improved airway opening clearance accelerated recovery unconsciousness, suggest rescue-like efforts. Oxytocin neurons hypothalamic paraventricular nucleus respond differentially presence of versus active their activation, along with oxytocin signaling, required for reviving-like actions. This tendency members may enhance group cohesion survival species.

Language: Английский

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Viral tools for neuroscience

Nature reviews. Neuroscience, Journal Year: 2020, Volume and Issue: 21(12), P. 669 - 681

Published: Oct. 27, 2020

Language: Английский

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Organization of the inputs and outputs of the mouse superior colliculus

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: June 28, 2021

The superior colliculus (SC) receives diverse and robust cortical inputs to drive a range of cognitive sensorimotor behaviors. However, it remains unclear how descending input arising from higher-order associative areas coordinate with SC networks influence its outputs. Here, we construct comprehensive map all cortico-tectal projections identify four collicular zones differential inputs: medial (SC.m), centromedial (SC.cm), centrolateral (SC.cl) lateral (SC.l). Further, delineate the distinctive brain-wide input/output organization each zone, assemble multiple parallel cortico-tecto-thalamic subnetworks, somatotopic in that displays distinguishable spatial properties maps neocortex basal ganglia. Finally, characterize interactions between those cortico-basal ganglia-thalamic subnetworks. This study provides structural basis for understanding is involved integrating different sensory modalities, translating information motor command, coordinating actions goal-directed

Language: Английский

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