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

Hwang, Kyoung-Doo; Baek, Jong Hwan; Ryu, Hyun-Hee; Lee, Jaegeon; Shim, Hyun Geun; Kim, Sun Yong; Kim, Sang Jeong; Lee, Yong-Seok

doi:10.1016/j.celrep.2023.112291

Cited by 9 publications

(4 citation statements)

References 66 publications

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“…Opto- and chemogenetic manipulations of the direct FN-PAG pathway during fear acquisition training resulted in alterations in retrieval and extinction learning without abnormalities in freezing behavior during acquisition training. Likewise, optogenetic manipulation of cerebellar nuclei neurons projecting to the lateral parabrachial nucleus resulted in altered fear retrieval ( Hwang et al, 2023 ).…”

Section: Discussionmentioning

confidence: 99%

Mild Deficits in Fear Learning: Evidence from Humans and Mice with Cerebellar Cortical Degeneration

Batsikadze,

Pakusch,

Klein

et al. 2024

eNeuro

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Functional brain imaging studies in humans suggest involvement of the cerebellum in fear conditioning, but do not allow conclusions about the functional significance. The main aim of the present study was to examine whether patients with cerebellar degeneration show impaired fear conditioning and whether this is accompanied by alterations in cerebellar cortical activations. To this end, a two-day differential fear conditioning study was conducted in 20 cerebellar patients and 21 control subjects using a 7-Tesla (7T) MRI system. Fear acquisition and extinction training were performed on day 1, followed by recall on day 2. Cerebellar patients learned to differentiate between the CS+ and CS-. Acquisition and consolidation of learned fear, however, was slowed. Additionally, extinction learning appeared to be delayed. The fMRI signal was reduced in relation to the prediction of the aversive stimulus and altered in relation to its unexpected omission. Similarly, mice with cerebellar cortical degeneration (spinocerebellar ataxia type 6, SCA6) were able to learn the fear association, but retrieval of fear memory was reduced. In sum, cerebellar cortical degeneration led to mild abnormalities in the acquisition of learned fear responses in both humans and mice, particularly manifesting post-acquisition training. Future research is warranted to investigate the basis of altered fMRI signals related to fear learning.Significance StatementHumans and mice with pure cerebellar cortical degeneration showed deficits in the acquisition of learned fear, but abnormalities were mild. Given that cerebellar fMRI signals predominantly reflect mossy fiber input, changes in cerebellar activations suggest that input signals related to the prediction and unexpected omission of the aversive US are altered in patients with cerebellar cortical degeneration. Importantly, these differences cannot be explained by cerebellar atrophy because cerebellar fMRI signal related to the presentation of the aversive stimulus (US) was not significantly different from controls. Future research is warranted to study the exact nature of cerebellar input signals related to fear learning.

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Section: Discussionmentioning

confidence: 99%

Mild Deficits in Fear Learning: Evidence from Humans and Mice with Cerebellar Cortical Degeneration

Batsikadze,

Pakusch,

Klein

et al. 2024

eNeuro

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“…There is substantial evidence that the cerebellum has extensive fibrous projection with parabrachial nucleus, and those projections involve in modulating classical fear conditioning. 53,54 However, future basic experiments are needed to verify the specific role of these related projections in headache, pain, and fear memories.…”

Section: The Parabrachial Nucleus In Headache and Painmentioning

confidence: 99%

Altered functional connectivity of brainstem nuclei in new daily persistent headache: Evidence from resting‐state functional magnetic resonance imaging

Wang,

Qiu,

Mei

et al. 2024

CNS Neurosci Ther

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ObjectivesThe new daily persistent headache (NDPH) is a rare primary headache disorder. However, the underlying mechanisms of NDPH remain incompletely understood. This study aims to apply seed‐based analysis to explore the functional connectivity (FC) of brainstem nuclei in patients with NDPH using resting‐state functional magnetic resonance imaging (MRI).MethodsThe FC analysis from the region of interest (ROI) to whole brain voxels was used to investigate 29 patients with NDPH and 37 well‐matched healthy controls (HCs) with 3.0 Tesla MRI. The 76 nuclei in the brainstem atlas were defined as ROIs. Furthermore, we explored the correlations between FC and patients' clinical characteristics and neuropsychological evaluations.ResultsPatients with NDPH exhibited reduced FC in multiple brainstem nuclei compared to HCs (including right inferior medullary reticular formation, right mesencephalic reticular formation, bilateral locus coeruleus, bilateral laterodorsal tegmental nucleus‐central gray of the rhombencephalon, median raphe, left medial parabrachial nucleus, periaqueductal gray, and bilateral ventral tegmental area‐parabrachial pigmented nucleus complex) and increased FC in periaqueductal gray. No significant correlations were found between the FC of these brain regions and clinical characteristics or neuropsychological evaluations after Bonferroni correction (p > 0.00016).ConclusionsOur results demonstrated that patients with NDPH have abnormal FC of brainstem nuclei involved in the perception and regulation of pain and emotions.

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“…The importance of such a brain-wide loop structure in which a cerebellum is involved has been recently raised and integrated into ANN models (Iwadate et al, 2014 ; Tanaka et al, 2020 ; Boven et al, 2023 ). Furthermore, in recent decades, our understanding of the cerebellum and its functions has deepened considerably, including the non-motor output from the cerebellum (Kang et al, 2021 ; Hwang et al, 2023 ) and multi-dimensional structural organization (Apps et al, 2018 ; Beckinghausen and Sillitoe, 2019 ). Although, currently, we barely understand the detailed network architecture underlying such diverse functions and gross anatomy, further research will lead us to implement the control of broad behavioral modality through the cerebellum.…”

Section: Outcome Of Optimization: Network Architecturementioning

confidence: 99%

Distinctive properties of biological neural networks and recent advances in bottom-up approaches toward a better biologically plausible neural network

Jeon

Kim

2023

Front. Comput. Neurosci.

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Although it may appear infeasible and impractical, building artificial intelligence (AI) using a bottom-up approach based on the understanding of neuroscience is straightforward. The lack of a generalized governing principle for biological neural networks (BNNs) forces us to address this problem by converting piecemeal information on the diverse features of neurons, synapses, and neural circuits into AI. In this review, we described recent attempts to build a biologically plausible neural network by following neuroscientifically similar strategies of neural network optimization or by implanting the outcome of the optimization, such as the properties of single computational units and the characteristics of the network architecture. In addition, we proposed a formalism of the relationship between the set of objectives that neural networks attempt to achieve, and neural network classes categorized by how closely their architectural features resemble those of BNN. This formalism is expected to define the potential roles of top-down and bottom-up approaches for building a biologically plausible neural network and offer a map helping the navigation of the gap between neuroscience and AI engineering.

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

Cited by 9 publications

References 66 publications

Mild Deficits in Fear Learning: Evidence from Humans and Mice with Cerebellar Cortical Degeneration

Mild Deficits in Fear Learning: Evidence from Humans and Mice with Cerebellar Cortical Degeneration

Altered functional connectivity of brainstem nuclei in new daily persistent headache: Evidence from resting‐state functional magnetic resonance imaging

Distinctive properties of biological neural networks and recent advances in bottom-up approaches toward a better biologically plausible neural network

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