
タンパク質凝集体による神経細胞の損傷を抑制する細胞間の応答メカニズムが明らかになった。


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Cell-to-cell tunnels rescue neurons from degeneration

タンパク質凝集体による神経細胞の変性を抑制する細胞間トンネル

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小脳歯状核ニューロンは、視覚的刺激の方向と関連する眼球運動の方向を動的にエンコードする。これは、小脳と大脳皮質の機能的なフィードバックループの一部を反映している。


The role of cerebellum in controlling eye movements is well established, but its contribution to more complex forms of visual behavior has remained elusive. To study cerebellar activity during visual attention we recorded extracellular activity of dentate nucleus (DN) neurons in two non-human primates (NHPs). NHPs were trained to read the direction indicated by a peripheral visual stimulus while maintaining fixation at the center, and report the direction of the cue by performing a saccadic eye movement into the same direction following a delay. We found that single unit DN neurons modulated spiking activity over the entire time-course of the task, and that their activity often bridged temporally separated intra-trial events, yet in a heterogeneous manner. To better understand the heterogeneous relationship between task structure, behavioral performance and neural dynamics, we constructed a behavioral, an encoding and a decoding model. Both NHPs showed different behavioral strategies, which influenced the performance. Activity of the DN neurons reflected the unique strategies, with the direction of the visual stimulus frequently being encoded long before an upcoming saccade. Retrograde labeling of the recording location indicated that these neurons receive predominantly inputs from Purkinje cells in the lateral cerebellum as well as neurons of the principal olive and medial pons, all regions known to connect with neurons in the prefrontal cortex contributing to planning of saccades. Together, our results highlight that DN neurons can dynamically modulate their activity during a visual attention task, comprising not only sensorimotor but also cognitive attentional components.

### Competing Interest Statement

The authors have declared no competing interest.

Encoding of cerebellar dentate neuronal activity during visual attention in rhesus macaques

視覚的注意課題中のサル小脳歯状核ニューロン活動のエンコーディング


うつ病患者の脳では、前頭-線条体サリエンスネットワークが通常の約2倍に拡大しており、これは気分状態に影響されず、発症前の子供でも検出可能な特徴である。また、この前頭-線条体回路の接続性の変化は、特定の症状の変化と関連し、将来のアンヘドニア症状を予測できる。


Precision functional mapping shows that the frontostriatal salience network occupies nearly twice as much of the cortex in people with depression, and this was unaffected by mood changes and detected in children before onset of symptoms.

Frontostriatal salience network expansion in individuals in depression - Nature

うつ病患者における前頭-線条体サリエンスネットワークの拡大


痛みの表情は、痛みに関連する脳活動の独自の情報を伝えるものである。


Pain is a private experience observable through various verbal and non-verbal behavioural manifestations, each of which may relate to different pain-related functions. Despite the importance of understanding the cerebral mechanisms underlying those manifestations, there is currently limited knowledge on the neural correlates of the facial expression of pain. In this functional magnetic resonance imaging (fMRI) study, noxious heat stimulation was applied in healthy volunteers and we tested if previously published brain signatures of pain were sensitive to pain expression. We then applied a multivariate pattern analysis to the fMRI data to predict the facial expression of pain. Results revealed the inability of previously developed pain neurosignatures to predict the facial expression of pain. We thus propose a Facial Expression of Pain Signature (FEPS) conveying distinctive information about the brain response to nociceptive stimulations with minimal or no overlap with other pain-relevant brain signatures associated with nociception, pain ratings, thermal pain aversiveness, or pain valuation. The FEPS may provide a distinctive functional characterization of the distributed cerebral response to nociceptive pain associated with the socio-communicative role of non-verbal pain expression. This underscores the complexity of pain phenomenology by reinforcing the view that neurosignatures conceived as biomarkers must be interpreted in relation to the specific pain manifestation(s) predicted and their underlying function(s). Future studies should explore other pain-relevant manifestations and assess the specificity of the FEPS against simulated pain expressions and other types of aversive or emotional states.

### Competing Interest Statement

The authors have declared no competing interest.

Participants did not provide informed consent for the sharing of individual data but unthresholded group maps are available upon request. Unthresholded and thresholded FEPS patterns are available on Neurovault (<https://neurovault.org/collections/13924/>). The SIIPS-1, the PVP and the TPAS are available on Github ([https://github.com/canlab/Neuroimaging\_Pattern\_Masks][1]). The NPS is available upon request from T.D.W.

 [1]: https://github.com/canlab/Neuroimaging_Pattern_Masks

A distributed brain response predicting the facial expression of acute nociceptive pain

痛みの表情は脳の痛み処理における特徴的な行動マーカーである


ドパミンはニューロン活動依存的にタンパク質合成を増加させ、これにより新たに合成されたタンパク質がドパミン依存性LTPの発現に必要となる。


The reward and novelty related neuromodulator dopamine plays an important role in hippocampal long-term memory, which is thought to involve protein synthesis-dependent synaptic plasticity. However, the direct effects of dopamine on protein synthesis, and the functional implications of newly synthesized proteins for synaptic plasticity, have not yet been investigated. We have previously reported that timing-dependent synaptic depression (t-LTD) can be converted into potentiation by dopamine application during synaptic stimulation (Brzsoko et al., 2015) or postsynaptic burst activation ([Fuchsberger et al., 2022][1]). Here we show that dopamine increases protein synthesis in mouse hippocampal CA1 neurons, enabling dopamine-dependent long-term potentiation (DA-LTP). We found that neuronal activity is required for the dopamine-induced increase in protein synthesis, which is mediated via the Ca2+-sensitive adenylate cyclase (AC) subtypes 1/8, cAMP, and cAMP-dependent protein kinase (PKA). Furthermore, dopamine induced a protein synthesis-dependent increase in the AMPA receptor subunit GluA1, but not GluA2. We found that DA-LTP is absent in GluA1 knock-out mice and that it requires calcium-permeable AMPA receptors. Taken together, our results suggest that dopamine together with neuronal activity controls synthesis of plasticity-related proteins, including GluA1, which enable DA-LTP via a signalling pathway distinct from that of conventional LTP.

### Competing Interest Statement

The authors have declared no competing interest.

 [1]: #ref-16

Dopamine increases protein synthesis in hippocampal neurons enabling dopamine-dependent LTP

ドパミンはタンパク質合成を増加させ-ドパミン依存性ltpを可能にする


ドパミンはタンパク質合成を増加させ、ドパミン依存性LTPを可能にする



高齢者と難聴者は、複数話者の発話を理解する際に、短時間的スケールと長時間的スケールの両方で処理の困難に直面する。


Comprehending speech requires deciphering a range of linguistic representations, from phonemes to narratives. Prior research suggests that in single-talker scenarios, the neural encoding of linguistic units follows a hierarchy of increasing temporal receptive windows. Shorter temporal units like phonemes and syllables are encoded by lower-level sensory brain regions, whereas longer units such as sentences and paragraphs are processed by higher-level perceptual and cognitive areas. However, the brain’s representation of these linguistic units under challenging listening conditions, such as a cocktail party situation, remains unclear. In this study, we recorded electroencephalogram (EEG) responses from both normal-hearing and hearing-impaired participants as they listened to individual and dual speakers narrating different parts of a story. The inclusion of hearing-impaired listeners allowed us to examine how hierarchically organized linguistic units in competing speech streams affect comprehension abilities. We leveraged a hierarchical language model to extract linguistic information at multiple levels—phoneme, syllable, word, phrase, and sentence—and aligned these model activations with the EEG data. Our findings showed distinct neural responses to dual-speaker speech between the two groups. Specifically, compared to normal-hearing listeners, hearing-impaired listeners exhibited poorer model fits at the acoustic, phoneme, and syllable levels as well as the sentence levels, but not at the word and phrase levels. These results suggest that hearing-impaired listeners experience disruptions at both shorter and longer temporal scales, while their processing at medium temporal scales remains unaffected.

### Competing Interest Statement

The authors have declared no competing interest.

Multi-talker speech comprehension at different temporal scales in listeners with normal and impaired hearing

高齢者と難聴者における複数話者の発話理解の神経基盤


意識レベルの変化に伴い、脳活動の流体力学的特性と応答性が変化する。


Signatures of consciousness are found in spectral and temporal properties of neuronal activity. Among these, spatiotemporal complexity after a perturbation has recently emerged as a robust metric to infer levels of consciousness. Perturbation paradigms remain, however, difficult to perform routinely. To discover alternative paradigms and metrics we systematically explore brain stimulation and resting-state activity in a digital brain twin model. We find that perturbational complexity only occurs when the brain model operates within a specific dynamical regime, in which spontaneous activity produces a large degree of functional network reorganizations referred to as being fluid. The regime of high brain fluidity is characterized by a small battery of metrics drawn from dynamical systems theory and predicts the impact of consciousness altering drugs (Xenon, Propofol and Ketamine). We validate the predictions in a cohort of 15 subjects at various stages of consciousness and demonstrate their agreement with previously reported perturbational complexity, but in a more accessible paradigm. Beyond the facilitation in clinical use, the metrics highlights complexity properties of brain dynamics in support of emergence of consciousness.

### Competing Interest Statement

The authors have declared no competing interest.

Spatiotemporal brain complexity quantifies consciousness outside of perturbation paradigms

大規模脳活動の流体力学的特徴と意識との関連性


脳は内部モデルを使って感覚を予測し、予測と実際の感覚の違いを検出することで、予期せぬ出来事に注意を向けることができる。この予測誤差信号の生成には、視床と大脳皮質の協調的な抑制回路機構が重要な役割を果たしている。


Experiments in mice show that a cortico-thalamic circuit generates prediction-error signals&nbsp;in primary visual cortex that amplify visual input&nbsp;that deviates from animals’&nbsp;expectations.

Cooperative thalamocortical circuit mechanism for sensory prediction errors - Nature

予測誤差を生成する視床皮質回路機構


嗅覚系の発達期には、嗅覚経験によって神経回路の構造と機能が長期的に変化する。この可塑性には、嗅覚グリア細胞のDraper受容体が重要な役割を果たす。


Sensory experience during developmental critical periods has lifelong consequences for circuit function and behavior, but the molecular and cellular mechanisms through which experience causes these changes are not well understood. The Drosophila antennal lobe houses synapses between olfactory sensory neurons (OSNs) and downstream projection neurons (PNs) in stereotyped glomeruli. Many glomeruli exhibit structural plasticity in response to early-life odor exposure, indicating a general sensitivity of the fly olfactory circuitry to early sensory experience. We recently found that glia regulate the development of the antennal lobe in young adult flies, leading us to ask if glia also drive experience-dependent plasticity. Here we define a critical period for structural and functional plasticity of OSN-PN synapses in the ethyl butyrate (EB)-sensitive glomerulus VM7. EB exposure for the first two days post-eclosion drives large-scale reductions in glomerular volume, presynapse number, and post-synaptic activity. The highly conserved engulfment receptor Draper is required for this critical period plasticity. Specifically, ensheathing glia upregulate Draper expression, invade the VM7 glomerulus, and phagocytose OSN presynaptic terminals in response to critical-period EB exposure. Crucially, synapse pruning during the critical period has long-term consequences for circuit function since both OSN-PN synapse number and spontaneous activity of PNs remain persistently decreased. These data demonstrate experience-dependent pruning of synapses in olfactory circuitry and argue that the Drosophila antennal lobe will be a powerful model for defining the function of glia in critical period plasticity.

### Competing Interest Statement

The authors have declared no competing interest.

Glia control experience-dependent plasticity in an olfactory critical period

早期生活における嗅覚経験が神経回路の可塑性を制御する


自由に泳ぐゼブラフィッシュの視床下部において、空間情報を表現するニューロン集団コードが発見された。これらのニューロンは、多様な感覚情報を統合し、柔軟に空間地図を形成することが示された。


Using a tracking microscope for freely moving animals, the authors discover a population of place cells in the zebrafish brain and demonstrate that a non-amniote brain is capable of integrating allothetic and idiothetic information to create a neural map of space.

A population code for spatial representation in the zebrafish telencephalon - Nature

自由に泳ぐゼブラフィッシュの脳内における空間表現のためのニューロン集団コード