
過夜の断食は、脅威の回避を容易にし、恐怖の消失を速める。これは、安全の予測誤差信号に関連する脳領域の活動低下によるものである。


coremsg

Excessive avoidance and slow extinction of fear are hallmarks of anxiety disorders. We have previously found that overnight fasting diminishes excessive avoidance and speeds up fear extinction by decreasing subjective relief during threat omissions. Since relief tracks the reward prediction error signal that governs safety learning, we hypothesized that these effects of fasting might be linked to a decreased activation in brain regions related to reward prediction error processing. Hence, we replicated our previous study in a 3T-MRI scanner. Overnight fasting increased effective avoidance and sped up fear extinction learning. During extinction, the fasting group showed lower activations in the ventromedial prefrontal cortex and nucleus accumbens in response to threat omissions signaled by a safe cue. Nucleus accumbens activations were modulated by relief in the control group. This study provides support for overnight fasting as an adjunct to treatments for anxiety, but the effects should be investigated in anxious patients.

### Competing Interest Statement

The authors have declared no competing interest.

Overnight fasting facilitates safety learning by changing the neurophysiological response to relief from threat omission

脅威の回避を容易にし-恐怖の消失を速める-過夜の断食が神経生理学的反応を変化させることで


脅威の回避を容易にし、恐怖の消失を速める:過夜の断食が神経生理学的反応を変化させることで


title_rewrite


腹側傍顔面領域(pFL)の異なる部位にビククリンを注入することで、能動呼吸の発生に関与する中心領域が特定された。特に、顔面神経核尾側端より前方0.6 mm及び0.8 mmの部位で最も強力かつ持続的な呼吸反応が観察された。


The lateral parafacial area (pFL) is a crucial region involved in respiratory control, particularly in generating active expiration through an expiratory oscillatory network. Active expiration involves rhythmic abdominal (ABD) muscle contractions during late- expiration, increasing ventilation during elevated respiratory demands. The precise anatomical location of the expiratory oscillator within the ventral medulla’s rostro-caudal axis is debated. While some studies point to the caudal tip of the facial nucleus (VIIc) as the oscillator’s core, others suggest more rostral areas. Our study employed bicuculline (a GABA-A receptor antagonist) injections at various pFL sites (-0.2 to +0.8mm from VIIc) to investigate the impact of GABAergic disinhibition on respiration. These injections consistently elicited ABD recruitment, but the response strength varied along the rostro-caudal zone. Remarkably, the most robust and enduring changes in tidal volume, minute ventilation and combined respiratory responses occurred at more rostral pFL locations (+0.6/+0.8 mm from VIIc). Multivariate analysis of the respiratory cycle further differentiated between locations, revealing the core site for active expiration generation with this experimental approach. Our study advances our understanding of neural mechanisms governing active expiration and emphasizes the significance of investigating the rostral pFL region.

### Competing Interest Statement

The authors have declared no competing interest.

Mapping responses to focal injections of bicuculline in the lateral parafacial region identifies core regions for maximal generation of active expiration

呼吸制御における腹側傍顔面領域の機能的マッピング-最大の能動呼吸発生に関与する中心領域の特定


呼吸制御における腹側傍顔面領域の機能的マッピング - 最大の能動呼吸発生に関与する中心領域の特定



中脳前野のニューロテンシン神経細胞は、GABA放出による抑制作用と、ニューロテンシン受容体活性化による興奮作用の相反する影響を及ぼし、体温調節に重要な役割を果たしている。


Neurotensin (Nts) is a neuropeptide acting as a neuromodulator in the brain. Pharmacological studies have identified Nts as a potent hypothermic agent. The medial preoptic area, a region that plays an important role in the control of thermoregulation, contains a high density of neurotensinergic neurons and Nts receptors. The conditions in which neurotensinergic neurons play a role in thermoregulation are not known. In this study optogenetic stimulation of preoptic Nts neurons induced a small hyperthermia. In vitro , optogenetic stimulation of preoptic Nts neurons resulted in synaptic release of GABA and net inhibition of the preoptic pituitary adenylate cyclase-activating polypeptide (PACAP) neurons firing activity. GABA-A receptor antagonist or genetic deletion of VGAT in Nts neurons unmasked also an excitatory effect that was blocked by a Nts receptor 1 antagonist. Stimulation of preoptic Nts neurons lacking VGAT resulted in excitation of PACAP neurons and hypothermia. Mice lacking VGAT expression in Nts neurons presented changes in the fever response and in the responses to heat or cold exposure as well as an altered circadian rhythm of body temperature. Chemogenetic activation of all Nts neurons in the brain induced a 4-5 °C hypothermia, which could be blocked by Nts receptor antagonists in the preoptic area. Chemogenetic activation of preoptic neurotensinergic projections resulted in robust excitation of preoptic PACAP neurons. Taken together our data demonstrate that endogenously released Nts can induce potent hypothermia and that excitation of preoptic PACAP neurons is the cellular mechanism that triggers this response.

### Competing Interest Statement

The authors have declared no competing interest.

Opposing actions of co-released GABA and neurotensin on the activity of preoptic neurons and on body temperature

中脳前野ニューロテンシン神経細胞の活性化が体温調節に及ぼす相反する作用


パッチクランプ法の手動操作の煩雑さと時間のかかる問題を解決するため、複数のパッチクランプ電極を協調的に制御する新しい手法「パッチウォーキング」を開発し、その有効性を実証した。


Significant technical challenges exist when measuring synaptic connections between neurons in living brain tissue. The patch clamping technique, when used to probe for synaptic connections, is manually laborious and time-consuming. To improve its efficiency, we pursued another approach: instead of retracting all patch clamping electrodes after each recording attempt, we cleaned just one of them and reused it to obtain another recording while maintaining the others. With one new patch clamp recording attempt, many new connections can be probed. By placing one pipette in front of the others in this way, one can “walk” across the tissue, termed “patch-walking.” We performed 136 patch clamp attempts for two pipettes, achieving 71 successful whole cell recordings (52.2%). Of these, we probed 29 pairs (i.e., 58 bidirectional probed connections) averaging 91 µ m intersomatic distance, finding 3 connections. Patch-walking yields 80-92% more probed connections, for experiments with 10-100 cells than the traditional synaptic connection searching method.

Motivation Recognizing the manual labor and time-intensive nature of patch clamping when trying to find synaptic connections, we aim to improve its efficiency. We introduce a novel approach, termed “patch-walking,” where one patch clamping electrode is cleaned and reused, enabling the exploration of numerous connections with a single recording attempt and improving the efficiency of identifying synaptic connections.

### Competing Interest Statement

I.K., W.M.S, and C.R.F. are co-inventors on a patent describing pipette cleaning that is licensed by Sensapex.

Patch-walking: Coordinated multi-pipette patch clamp for efficiently finding synaptic connections

脳スライスにおける効率的な神経細胞間シナプス接続の探索のための協調型マルチパッチクランプ法


筋肉の運動単位プールの全体像を解明することで、運動ニューロンへの入力信号がどのように筋力に変換されるかが明らかになった。


To advance our understanding of the neural control of muscle, we decoded the firing activity of extensive samples of motor units in the Tibialis Anterior (129±44 per participant; n=8) and the Vastus Lateralis (130±63 per participant; n=8) during isometric contractions of up to 80% of maximal force. From this unique dataset, we characterised the rate coding of each motor unit as the relation between its instantaneous firing rate and the muscle force, with the assumption that the linear increase in isometric force reflects a proportional increase in the net synaptic excitatory inputs received by the motoneuron. This relation was characterised with a natural logarithm function that comprised two phases. The initial phase was marked by a steep acceleration of firing rate, which was greater for low-than medium- and high-threshold motor units. The second phase comprised a linear increase in firing rate, which was greater for high-than medium- and low-threshold motor units. Changes in firing rate were largely non-linear during the ramp-up and ramp-down phases of the task, but with significant prolonged firing activity only evident for medium-threshold motor units. Contrary to what is usually assumed, our results demonstrate that the firing rate of each motor unit can follow a large variety of trends with force across the pool. From a neural control perspective, these findings indicate how motor unit pools use gain control to transform inputs with limited bandwidths into an intended muscle force.

Significance statement Movements are performed by motoneurons transforming synaptic input into an activation signal that controls muscle force. The control signal is not linearly related to the net synaptic input, but instead emerges from interactions between ionotropic and neuromodulatory inputs to motoneurons. Critically, these interactions vary across motoneuron pools and differ between muscles. We decoded the activity of hundreds of motor units from electromyographic signals recorded in vivo in humans to derive the most comprehensive framework to date of motor unit activity during isometric contractions that spanned the entire operating range of two human leg muscles. Our results address several key gaps in knowledge in this field and, importantly, characterise the activity of entire motor unit populations for each muscle.

### Competing Interest Statement

The authors have declared no competing interest.

The decoding of extensive samples of motor units in human muscles reveals the rate coding of entire motoneuron pools

筋肉の運動単位の広範な解析により明らかになった全運動ニューロンプールの発火率制御


加齢に伴い、交感神経運動ニューロンの固有の電気的特性が変化し、過活動を引き起こすことが示された。特に、KCNQ電流の減少が重要な役割を果たしている。


Overactivity of the sympathetic nervous system is a hallmark of aging. The cellular mechanisms behind this overactivity remain poorly understood, with most attention paid to likely central nervous system components. In this work, we hypothesized that aging also affects the function of motor neurons in the peripheral sympathetic ganglia. To test this hypothesis, we compared the electrophysiological responses and ion-channel activity of neurons isolated from the superior cervical ganglia of young (12 weeks), middle-aged (64 weeks), and old (115 weeks) mice. These approaches showed that aging does impact the intrinsic properties of sympathetic motor neurons, increasing spontaneous and evoked firing responses. A reduction of KCNQ channel currents emerged as a major contributor to age-related hyperexcitability. Thus, it is essential to consider the effect of aging on motor components of the sympathetic reflex as a crucial part of the mechanism involved in sympathetic overactivity.

### Competing Interest Statement

The authors have declared no competing interest.

Sympathetic Motor Neuron Dysfunction is a Missing Link in Age-Associated Sympathetic Overactivity

加齢に伴う交感神経過活動の欠落した要因は-交感神経運動ニューロンの機能障害である


加齢に伴う交感神経過活動の欠落した要因は、交感神経運動ニューロンの機能障害である
