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

---

Prediction signals in the cerebellum: Beyond supervised motor learning

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

Published: March 24, 2020

While classical views of cerebellar learning have suggested that this structure predominantly operates according to an error-based supervised rule refine movements, emerging evidence suggests the cerebellum may also harness a wider range rules contribute variety behaviors, including cognitive processes. Together, such points broad role for circuits in generating and testing predictions about movement, reward, other non-motor operations. However, expanded view processing raises many new questions how apparent diversity function arises from with striking homogeneity. Hence, review will highlight both current predictive circuit extends beyond error-driven learning, as well open must be addressed unify our understanding function.

Language: Английский

---

Classical conditioning drives learned reward prediction signals in climbing fibers across the lateral cerebellum

eLife, Journal Year: 2019, Volume and Issue: 8

Published: Sept. 11, 2019

Classical models of cerebellar learning posit that climbing fibers operate according to a supervised rule instruct changes in motor output by signaling the occurrence movement errors. However, is also associated with non-motor behaviors, and recently modulating reward association pathways VTA. To test how cerebellum processes related signals same type classical conditioning behavior typically studied evaluate processing VTA striatum, we have used calcium imaging visualize instructional carried across lateral mice before after learning. We find distinct fiber responses three regions can each signal prediction. These are well suited guide based on expectation enable contribution driven suggesting broad role for reward-based

Language: Английский

---

Ephaptic Coupling Promotes Synchronous Firing of Cerebellar Purkinje Cells

Neuron, Journal Year: 2018, Volume and Issue: 100(3), P. 564 - 578.e3

Published: Oct. 4, 2018

Language: Английский

---

Bidirectional learning in upbound and downbound microzones of the cerebellum

Nature reviews. Neuroscience, Journal Year: 2020, Volume and Issue: 22(2), P. 92 - 110

Published: Nov. 17, 2020

Language: Английский

---

Microglia-Triggered Plasticity of Intrinsic Excitability Modulates Psychomotor Behaviors in Acute Cerebellar Inflammation

Cell Reports, Journal Year: 2019, Volume and Issue: 28(11), P. 2923 - 2938.e8

Published: Sept. 1, 2019

Cerebellar dysfunction relates to various psychiatric disorders, including autism spectrum and depressive disorders. However, the physiological aspect is less advanced. Here, we investigate immune-triggered hyperexcitability in cerebellum on a wider scope. Activated microglia via exposure bacterial endotoxin lipopolysaccharide or heat-killed Gram-negative bacteria induce potentiation of intrinsic excitability Purkinje neurons, which suppressed by microglia-activity inhibitor depletion. An inflammatory cytokine, tumor necrosis factor alpha (TNF-α), released from toll-like receptor 4, triggers this plasticity. Our two-photon FRET ATP imaging shows an increase concentration following exposure. Both TNF-α secretion facilitate synaptic transmission. Region-specific inflammation vivo depression- autistic-like behaviors. Furthermore, both inhibition depletion revert such behavioral abnormality. Resting-state functional MRI reveals overconnectivity between inflamed prefrontal neocortical regions. Thus, immune activity induces neuronal disruption psychomotor behaviors animals.

Language: Английский

---

Cerebellar modulation of synaptic input to freezing-related neurons in the periaqueductal gray

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

Published: March 24, 2020

Innate defensive behaviors, such as freezing, are adaptive for avoiding predation. Freezing-related midbrain regions project to the cerebellum, which is known regulate rapid sensorimotor integration, raising question of cerebellar contributions freezing. Here, we find that neurons mouse medial (fastigial) nuclei (mCbN), fire spontaneously with wide dynamic ranges, send glutamatergic projections ventrolateral periaqueductal gray (vlPAG), contains diverse cell types. In freely moving mice, optogenetically stimulating vlPAG express Chx10 reliably induces slices, mCbN terminals excite ~20% positive or GAD2 and ~70% dopaminergic TH-positive neurons. Stimulating either afferents TH augments IPSCs suppresses EPSCs in by activating postsynaptic D

Language: Английский

---

The cerebellum and epilepsy

Epilepsy & Behavior, Journal Year: 2020, Volume and Issue: 121, P. 106909 - 106909

Published: Feb. 5, 2020

Language: Английский

---

VTA-projecting cerebellar neurons mediate stress-dependent depression-like behaviors

eLife, Journal Year: 2022, Volume and Issue: 11

Published: Feb. 14, 2022

Although cerebellar alterations have been implicated in stress symptoms, the exact contribution of cerebellum to symptoms remains be elucidated. Here, we demonstrated crucial role neurons projecting ventral tegmental area (VTA) development chronic stress-induced behavioral mice. Chronic chemogenetic activation inhibitory Purkinje cells crus I suppressed c-Fos expression DN and an increase immobility tail suspension test or forced swimming test, which were triggered by application. The combination adeno-associated virus-based circuit mapping electrophysiological recording identified network connections from VTA via dentate nucleus (DN) deep nuclei. Furthermore, inhibition specific that project prevented stressed mice showing such depression-like behavior, whereas these alone changes comparable with behaviors Our results indicate VTA-projecting proactively regulate raising possibility may effective target for prevention depressive disorders human.

Language: Английский

---

The Cerebellar Cortex

Annual Review of Neuroscience, Journal Year: 2022, Volume and Issue: 45(1), P. 151 - 175

Published: July 8, 2022

The cerebellar cortex is an important system for relating neural circuits and learning. Its promise reflects the longstanding idea that it contains simple, repeated circuit modules with only a few cell types single plasticity mechanism mediates learning according to classical Marr-Albus models. However, emerging data have revealed surprising diversity in neuron types, synaptic connections, mechanisms, both locally regionally within cortex. In light of these findings, not attempts generate holistic model across different behaviors been successful. While cerebellum remains ideal linking neuronal function behavior, necessary update framework achieve its great promise. this review, we highlight recent advances our understanding cerebellar-cortical signaling forms enrich processing.

Language: Английский

---