
Subcellularly restricted non-lethal caspase activation is regulated by the proximity of executioner caspases to specific membrane proteins, such as the Fasciclin 3 isoform G, which promotes the expression and recruitment of the initiator caspase Dronc.


coremsg

The nervous system undergoes functional modification independent on cell turn over. Caspase participates in reversible neuronal modulation via non-lethal activation. However, the mechanism that enables non-lethal activation remains unclear. Here, we analyzed proximal proteins of Drosophila executioner caspase in the adult brain using TurboID. We discovered that executioner caspase Drice is, as an inactive proform, proximal to cell membrane proteins, including a specific splicing isoform of cell adhesion molecule Fasciclin 3 (Fas3), Fas3G. To investigate whether sequestration of executioner caspase to plasma membrane of axons is the mechanism for non-lethal activation, we developed a Gal4-Manipulated Area-Specific CaspaseTracker/CasExpress system for sensitive monitoring of caspase activity near plasma membrane. We demonstrated that Fas3G -overexpression promotes caspase activation in olfactory receptor neurons without killing them, by inducing expression of initiator caspase Dronc, which also comes close to Fas3G. Physiologically, Fas3G -overexpression facilitated non-lethal activation suppresses innate olfactory attraction behavior. Our findings suggest that subcellularly-restricted caspase activation, defined by caspase proximal proteins, is the mechanism for non-lethal activation, opening the methodological development of reversible modification of neuronal function via regulating caspase proximal proteins.

### Competing Interest Statement

The authors have declared no competing interest.

Executioner caspase is proximal to Fasciclin 3 which facilitates non-lethal activation in Drosophila olfactory receptor neurons

proximity-based-regulation-of-non-lethal-caspase-activation-in-drosophila-olfactory-receptor-neurons


Proximity-Based Regulation of Non-Lethal Caspase Activation in Drosophila Olfactory Receptor Neurons


title_rewrite


Glaucoma-associated mutations in the mitophagy receptor Optineurin (OPTN) increase the fraction of stationary mitochondria, OPTN, and LC3b within retinal ganglion cell (RGC) axons, as well as the shedding of mitochondria from axons and their subsequent degradation by surrounding astrocytes.


We previously described a process referred to as transmitophagy where mitochondria shed by retinal ganglion cell (RGC) axons are transferred to and degraded by surrounding astrocytes in the optic nerve head of mice. Since the mitophagy receptor Optineurin (OPTN) is one of few large- effect glaucoma genes and axonal damage occurs at the optic nerve head in glaucoma, here we explored whether OPTN mutations perturb transmitophagy. Live-imaging of Xenopus laevis optic nerves revealed that diverse human mutant but not wildtype OPTN increase stationary mitochondria and mitophagy machinery and their colocalization within, and in the case of the glaucoma-associated OPTN mutations also outside of, RGC axons. These extra-axonal mitochondria are degraded by astrocytes. Our studies support the view that in RGC axons under baseline conditions there are low levels of mitophagy, but that glaucoma-associated perturbations in OPTN result in increased axonal mitophagy involving the shedding and astrocytic degradation of the mitochondria.

![Figure][1]</img>

### Competing Interest Statement

The authors have declared no competing interest.

 [1]: pending:yes

Glaucoma-associated Optineurin mutations increase transmitophagy in a vertebrate optic nerve

glaucoma-associated-optineurin-mutations-increase-axonal-mitophagy-and-shedding-of-mitochondria-in-a-vertebrate-optic-nerve-model


Glaucoma-associated Optineurin Mutations Increase Axonal Mitophagy and Shedding of Mitochondria in a Vertebrate Optic Nerve Model



마우스 소뇌 피질에서 tDCS는 신경세포의 소마-수상돌기 방향에 따라 다양한 방식으로 활성을 변조한다.


Transcranial direct-current stimulation (tDCS) of the cerebellum is a promising non-invasive neuromodulatory technique being proposed for the treatment of neurological and neuropsychiatric disorders. However, there is a lack of knowledge about how externally applied currents affect neuronal spiking activity in cerebellar circuits in vivo . We investigated how Cb-tDCS affects the firing rate of Purkinje cells (PC) and non-PC in the mouse cerebellar cortex to understand the underlying mechanisms behind the polarity-dependent modulation of neuronal activity induced by tDCS.

Mice (n = 9) were prepared for the chronic recording of LFPs to assess the actual electric field gradient imposed by Cb-tDCS in our experimental design. Single-neuron extracellular recording of PCs in awake (n = 24) and anesthetized (n = 27) mice was combined with juxtacellular recordings and subsequent staining of PC with neurobiotin under anesthesia (n = 8) to correlate their neuronal orientation with their response to Cb-tDCS. Finally, a high-density Neuropixels recording system was used to demonstrate the relevance of neuronal orientation during the application of Cb-tDCS in awake mice (n = 6).

In this study, we observe that Cb-tDCS induces a heterogeneous polarity-dependent modulation of the firing rate of Purkinje cells (PC) and non-PC in the mouse cerebellar cortex. We demonstrate that the apparently heterogeneous effects of tDCS on PC activity can be explained by taking into account the somatodendritic orientation relative to the electric field. Our findings highlight the need to consider neuronal orientation and morphology to improve tDCS computational models, enhance stimulation protocol reliability, and optimize effects in both basic and clinical applications.

### Competing Interest Statement

The authors have declared no competing interest.

Somatodendritic orientation determines tDCS-induced neuromodulation of Purkinje cell activity in awake mice

마우스-각성-상태에서-소마-수상돌기-방향이-tdcs-유도-푸르키네-세포-활성-변조를-결정한다-


마우스 각성 상태에서 소마-수상돌기 방향이 tDCS 유도 푸르키네 세포 활성 변조를 결정한다.



The somatodendritic orientation of Purkinje cells in the mouse cerebellar cortex determines the polarity-dependent modulation of their firing rate in response to transcranial direct current stimulation (tDCS).


somatodendritic-orientation-determines-the-polarity-dependent-modulation-of-purkinje-cell-activity-by-transcranial-direct-current-stimulation-in-awake-mice


Somatodendritic Orientation Determines the Polarity-Dependent Modulation of Purkinje Cell Activity by Transcranial Direct Current Stimulation in Awake Mice



사람의 해마와 내측 측두엽 신경세포가 복잡한 이미지 제시 순서의 시간적 구조를 신속하게 인코딩하고, 이를 지속적으로 표현하며, 이를 통해 미래 자극의 확률을 예측한다.


Single-neuron recordings from intracranial electrodes inserted into human brains for clinical reasons suggest that the temporal structure of human experience is encoded in human hippocampal and entorhinal neurons.

Human hippocampal and entorhinal neurons encode the temporal structure of experience - Nature

사람의-해마와-내측-측두엽-신경세포가-경험의-시간적-구조를-인코딩하는-방식


사람의 해마와 내측 측두엽 신경세포가 경험의 시간적 구조를 인코딩하는 방식



A significant proportion of former professional football players believe they have chronic traumatic encephalopathy (CTE), which is associated with an increased risk of suicidal thoughts.


A stunning number of still-living former football players perceive chronic traumatic encephalopathy, with clinical implications.

One in Three Pro Football Players Think They Have CTE

one-third-of-former-professional-football-players-believe-they-have-chronic-traumatic-encephalopathy-cte-


One-Third of Former Professional Football Players Believe They Have Chronic Traumatic Encephalopathy (CTE)



척수 손상 후 상처 치유 과정에서 PDYN+ 세포가 분비하는 κ-아편 수용체 작용제가 CSF-cN 세포를 자극하여 상피 세포의 증식을 억제하는 내인성 신호 전달 경로가 존재한다.


Paracrine κ-opioid signalling among cells surrounding the spinal cord central canal modulates scar formation after injury.

Endogenous opioid signalling regulates spinal ependymal cell proliferation - Nature

척수-손상-후-상처-치유-과정에서-내인성-아편-신호-전달이-척수-상피-세포-증식을-조절한다


척수 손상 후 상처 치유 과정에서 내인성 아편 신호 전달이 척수 상피 세포 증식을 조절한다



脊髄損傷後の瘢痕形成は神経再生を阻害するため、その動的な調節が重要である。本研究は、ケイ-オピオイド受容体を発現する脳脊髄液接触ニューロンが、プロジニルフィンを産生する隣接細胞集団からのケイ-オピオイド刺激を受けて、上衣細胞の増殖を抑制する内因性のパラクライン伝達経路を明らかにした。


脊髄損傷後の瘢痕形成を調節する内因性オピオイド伝達経路の発見


Endogenous κ-opioid signaling pathway involving cerebrospinal fluid-contacting neurons and prodynorphin-expressing cells regulates ependymal cell proliferation and scar formation after spinal cord injury.


endogenous-opioid-signaling-regulates-spinal-ependymal-cell-proliferation-and-scar-formation-after-injury


Endogenous Opioid Signaling Regulates Spinal Ependymal Cell Proliferation and Scar Formation After Injury



뇌의 등쪽 운동 미주신경핵(DMV)이 장내 지방 흡수 과정을 조절하며, 이를 타겟으로 하는 천연 화합물 푸에라린이 지방 흡수를 감소시킬 수 있다.


Neurons in the dorsal motor nucleus of vagus are involved in the absorption of fat in the intestine, and the natural compound puerarin shows utility in modulating this brain–gut axis to reduce fat absorption.

A brain-to-gut signal controls intestinal fat absorption - Nature

뇌-장-신호가-장내-지방-흡수를-조절한다


뇌-장 신호가 장내 지방 흡수를 조절한다
