Cerebellar nuclei neurons projecting to the lateral parabrachial nucleus modulate classical fear conditioning

Cell Reports, Год журнала: 2023, Номер 42(4), С. 112291 - 112291

Опубликована: Март 22, 2023

Multiple brain regions are engaged in classical fear conditioning. Despite evidence for cerebellar involvement conditioning, the mechanisms by which outputs modulate learning and memory remain unclear. We identify a population of deep nucleus (DCN) neurons with monosynaptic glutamatergic projections to lateral parabrachial (lPBN) (DCN→lPBN neurons) mice. While optogenetic suppression DCN→lPBN impairs auditory memory, activation elicits freezing behavior only after Moreover, conditioning potentiates DCN-lPBN synapses, subsequently, cue activates lPBN Furthermore, neuron can replace but not footshock These findings demonstrate that nuclei via transmitting conditioned stimuli signals lPBN. Collectively, our suggest circuit is part neuronal substrates within interconnected underscoring memory.

Язык: Английский

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Partial restoration of brain dystrophin by tricyclo-DNA antisense oligonucleotides alleviates emotional deficits in mdx52 mice

Molecular Therapy — Nucleic Acids, Год журнала: 2023, Номер 32, С. 173 - 188

Опубликована: Март 21, 2023

The mdx52 mouse model recapitulates a frequent mutation profile associated with brain involvement in Duchenne muscular dystrophy. Deletion of exon 52 impedes expression two dystrophins (Dp427, Dp140) expressed brain, and is eligible for therapeutic exon-skipping strategies. We previously showed that mice display enhanced anxiety fearfulness, impaired associative fear learning. In this study, we examined the reversibility these phenotypes using 51 skipping to restore exclusively Dp427 mice. first show single intracerebroventricular administration tricyclo-DNA antisense oligonucleotides targeting restores 5%–15% dystrophin protein hippocampus, cerebellum, cortex, at stable levels between 7 11 week after injection. Anxiety unconditioned were significantly reduced treated acquisition conditioning appeared fully rescued, while memory tested 24 h later was only partially improved. Additional restoration skeletal cardiac muscles by systemic treatment did not further improve response, confirming central origin phenotype. These findings indicate some emotional cognitive deficits deficiency may be reversible or least improved partial postnatal rescue.

Язык: Английский

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Anatomy, histology, physiology, and connectivity of the cerebellum

Elsevier eBooks, Год журнала: 2025, Номер unknown, С. 1 - 19

Опубликована: Янв. 1, 2025

Язык: Английский

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Dual and plasticity-dependent regulation of cerebello-zona incerta circuits on anxiety-like behaviors

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Апрель 8, 2025

Clinical observation has identified cerebellar cognitive affective syndrome, which is characterized by various non-motor dysfunctions such as social disorders and anxiety. Increasing evidence revealed reciprocal mono-/poly-synaptic connections of cerebello-cerebral circuits, forming the concept connectome. In this study, we demonstrate that neurons in nuclei (CN) male mice project to a subset zona incerta (ZI) through long-range glutamatergic GABAergic transmissions, both capable encoding acute stress. Furthermore, activating or inhibiting transmissions CN → ZI pathway can positively negatively regulate anxiety place preference presynaptic plasticity-dependent mechanisms, well mediate motor-induced alleviation Our data support close relationship between cerebellum emotional processes suggest targeting outputs may be an effective approach for treating

Язык: Английский

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Region- and cell type-specific changes in gene expression in the cerebellum after classical fear conditioning

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Май 7, 2025

The cerebellum has recently been recognized for its role in non-motor functions, including classical fear conditioning. However, the molecular mechanisms underlying learning and memory remain largely unknown. Here, we investigate transcriptional changes associated with auditory Spatial transcriptomic analysis revealed that deep cerebellar nuclei (DCN), an output region of cerebellum, expression immediate early genes increased following retrieval, suggesting DCN may contribute to processing. As cortex, robust region-specific were observed, distinct patterns emerging across Purkinje cell layer vermis region. To further elucidate specific types involved processing, performed single-nucleus RNA sequencing identified prominent gene Kit + inhibitory neurons. Collectively, our findings highlight region- cell-type-specific adaptations providing insights into contribution learning.

Язык: Английский

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Unique neural signatures of childhood sexual abuse revisited

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Май 15, 2025

Childhood sexual abuse (CSA) constitutes a detrimental subtype of childhood maltreatment (CM) associated with high trauma load and adverse health outcomes. Previous studies indicate CSA-specific reductions in gray matter volume (GMV) cortical thickness. It remains challenging to disentangle brain alterations CSA from those related intensity or psychopathology. Here, we apply novel approach, comparing individuals CSA, non-sexual maltreatment, non-maltreated control group, identify findings. Drawing cohort n = 2039 depressed healthy men women allowed us match groups 1:1 for age, sex, depression diagnosis, and, maltreated groups, load. The Trauma Questionnaire was used assess maltreatment. Applying threshold-free cluster enhancement, investigated GMV thickness 195 adults compared non-sexually (nCSA, 195) (nCM, individuals. CSA showed larger the right cerebellum nCSA but not nCM. displayed encompassing bilateral superior frontal gyri, pre- postcentral supramarginal parietal cortices, precunei, insulae, both This is largest study investigate effects on morphometry, applying matched group comparisons. These findings highlight distinct neural signatures characterized by preserved regions also affected major depression, cerebellar types results underscore importance distinguishing between considering confounding factors when assessing their neurobiological impacts.

Язык: Английский

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A cognitive computing approach for product configuration design based on associative rule mining and deep reinforcement learning

International Journal of Production Research, Год журнала: 2024, Номер unknown, С. 1 - 24

Опубликована: Ноя. 21, 2024

Язык: Английский

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Intrinsic plasticity of Purkinje cell serves homeostatic regulation of fear memory

Molecular Psychiatry, Год журнала: 2023, Номер 29(2), С. 247 - 256

Опубликована: Ноя. 28, 2023

Язык: Английский

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RCPL preprint: An externally validated resting-state brain connectivity signature of pain-related learning

Опубликована: Окт. 6, 2023

Pain can be conceptualized as a precision signal for reinforcement learning in the brain and alterations these processes are hallmark of chronic pain conditions. Investigating individual differences pain-related therefore holds significant clinical translational relevance.Here, we developed externally validated novel resting-state connectivity-based predictive model learning. The pre-registered external validation indicated that proposed is specific pain, explains 8-12% inter-individual variance performance. Model redictions driven by connections amygdala, posterior insula, sensorimotor, frontoparietal cerebellar regions, outlining network commonlydescribed aversive pain. We propose resulting robust highly accessible biomarker candidate research, with promising implications personalized treatment approaches high potential to advance our understanding neural mechanisms

Язык: Английский

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Cerebellar contributions to fear-based emotional processing: relevance to understanding the neural circuits involved in autism

Frontiers in Systems Neuroscience, Год журнала: 2023, Номер 17

Опубликована: Ноя. 21, 2023

Cerebellar networks have traditionally been linked to sensorimotor control. However, a large body of evidence suggests that cerebellar functions extend non-motor realms, such as fear-based emotional processing and these are supported by interactions with wide range brain structures. Research related the contributions has focussed primarily on use well-constrained conditioning paradigms in both human non-human subjects. From studies, circuits appear be critically involved conditioned unconditioned responses threatening stimuli addition encoding storage fear memory. It hypothesised computational mechanism underlying this contribution may involve internal models, where errors between actual expected outcomes computed within circuitry cerebellum. clinical perspective, abnormalities consistently neurodevelopmental disorders, including autism. Importantly, atypical adaptive behaviour heightened anxiety also common amongst autistic individuals. In review, we provide an overview current anatomical, physiological theoretical understanding foster further insights into neural dysregulation observed people

Язык: Английский

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