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SARM1 executes neuronal parthanatos and promotes excitotoxic cell death 04/16/2026
Wu et al. show that PARP1 hyperactivation activates the NAD⁺ hydrolase SARM1 to execute neuronal parthanatos. SARM1 drives mitochondrial depolarization, AIF translocation, and neuronal death following DNA damage and other parthanatos-associated insults. These findings expand the therapeutic potential of SARM1 inhibitors to additional common neurodegenerative diseases.
Top-down control of the descending pain modulatory system drives multimodal placebo analgesia 04/16/2026
Livrizzi, Chang-Weinberg, et al. identify a cortical-brainstem circuit that mediates top-down control of pain during placebo analgesia and find that pain relief is gated by endogenous opioids in the vlPAG. They find that the placebo effect extends to multiple forms of pain and that pre-conditioning promotes pain resilience after injury.
A bidirectional brain-fat body axis for pathogen avoidance 04/16/2026
How immune tissues influence brain function remains unclear. Wang et al. show that pathogen sensing recruits neuromodulatory input to the fat body, triggering fat body-derived dopamine release that modulates mushroom body output neurons to drive pathogen avoidance.
Risk reshapes amygdala representation of choice 04/16/2026
Piantadosi et al. show mice flexibly adjust choices between reward options based on the punishment potential in a BLA-dependent manner. They find that BLA neuronal representation of punishment reactivates during risk-related behaviors. Additionally, they demonstrate that risk sensitivity versus tolerance is predictable from the risk-related recruitment of newly encoding neurons into the choice representation.