Missense variants in O-GlcNAc transferase (OGT) result in OGT congenital disorder of glycosylation (OGT-CDG), an intellectual disability syndrome associated with O-GlcNAc dyshomeostasis and a range of neurodevelopmental defects. Inhibition of O-GlcNAcase (OGA), the enzyme responsible for removing protein O-GlcNAcylation, has been explored as a target for modulating brain O-GlcNAc homeostasis in neurodegenerative diseases and may also be a target for OGT-CDG. Here, we describe an OGT-CDG mouse line, studied in male mice, that exhibits microcephaly, motor deficits, and brain O-GlcNAc dyshomeostasis, closely mirroring patient symptoms. We genetically explored OGA as a target for OGT-CDG by crossing these mice with a line carrying catalytically inactive OGA. Encouragingly, this partially restored O-GlcNAc homeostasis in brain and blood as determined by Ogt/Oga mRNA ratio. These findings suggest that OGA inhibition can modulate enzymatic imbalance in OGT-CDG mice possessing microcephaly and motor deficits and t...

The capacity of animals to rapidly and appropriately respond to potential threats is critical for survival. In many species, this involves innate defensive behaviors, such as flight or freezing. However, not all threats are dangerous. Habituation allows animals to filter out irrelevant stimuli and avoid unnecessary energy expenditure. While environmental context is known to modulate behavior in associative learning paradigms, it remains unclear whether this also applies to visually evoked defensive behaviors. Here, we address this question in mice of either sex by examining the role of environmental context on habituation of defensive responses to threatening visual stimuli. We developed a protocol that produces rapid (within minutes) and stable (lasting at least one week) habituation of freezing responses to slowly sweeping visual stimuli resembling an aerial predator moving across the sky. Using this protocol, we tested the impact of environmental context on habituation and found that changing the contex...

Huntington's disease (HD) is a hereditary neurodegenerative disease that typically presents during midlife and is characterized by a combination of motor, cognitive, and psychiatric symptoms. HD is fatal and arises from a mutation in the huntingtin ( HTT ) gene, which results in decreased neuronal health followed by brain atrophy, with spiny projection neurons (SPNs) of the striatum being especially vulnerable to degeneration. HTT loss of function, caused by haploinsufficiency of the wild-type HTT gene (wt HTT ), is an important feature of HD pathophysiology that has previously been understudied compared with mutant HTT gain-of-function mechanisms. wtHTT is essential for nervous system development and functions as a scaffolding protein to support many vital cellular functions including axonal transport, autophagy, and synaptic plasticity. Here, we examined the consequences of wtHTT deletion in the adult cortex and striatum by conditionally inactivating wtHTT in 2–4-month-old male and female Htt fl/fl mice....

Dysregulation of Ca2+ homeostasis in cochlear outer hair cells (OHCs) is associated with impaired hearing following noise exposure. Ca2+ signaling in developing OHCs is modulated by oncomodulin (OCM), an EF-hand calcium-binding protein. Here, we investigated whether the lack of OCM disrupts Ca2+ signaling in mature OHCs and influences vulnerability to moderate noise. Using young adult CBA/CaJ mice of either sex, we found that OHCs from Ocm knock-out ( Ocm−/− ) mice showed comparable electromotile responses and synaptic innervation compared with littermate controls. Prior to noise exposure, Ocm −/− mice had auditory brainstem responses with highly variable latencies and amplitudes compared with Ocm +/+ mice. Moderate noise exposure (95 dB SPL, 2 h) caused temporary threshold shifts in wild-type ( Ocm +/+) mice but PTS in Ocm −/− mice. Using a genetically encoded Ca2+ sensor (GCaMP6s) expressed in OHCs, we found increased GCaMP6s fluorescence and ATP-induced Ca2+ signaling in Ocm −/− OHCs. Using GCaMP6s mice...

Epidemiological studies show that only a minority of people exposed to addictive drugs develop addiction, suggesting that preexisting biological factors contribute to addiction vulnerability. Genome-wide association studies support this hypothesis by identifying genetic variants that are partially shared across different addictive drugs (Lai et al., 2026). Twin and family studies similarly indicate that addiction-related traits are heritable. For example, unaffected siblings of people with stimulant addiction show behavioral and neurobiological traits associated with addiction vulnerability, including impulsivity and impaired inhibitory control; these results suggest that inherited factors contribute to addiction risk even before drug exposure (Ersche et al., 2012). Although environmental influences and life experiences also contribute to addiction development, the biological mechanisms underlying vulnerability and resilience remain incompletely understood. One hypothesis is that individuals who develop a...

Adaptive goal-directed actions performed under threat require caution, often expressed as delayed response timing that balances urgency against error risk by allowing more time for evaluation. Although this temporal regulation is essential for survival, its neural mechanisms remain poorly understood. In mice of either sex, we show that glutamatergic neurons in the subthalamic nucleus (STN) regulate the timing of cued actions that avoid harm. Optogenetic activation of the STN, or its projections to the midbrain but not the globus pallidus, modulates action timing in a frequency-dependent manner, accelerating initiation such that animals lose the ability to respond cautiously, defer actions, or stop ongoing responses. STN excitation can also substitute for a natural cue and prevents the development of cautious responding, indicating a direct role in controlling avoidance action initiation timing. These effects were not driven by aversiveness, as mice did not avoid STN excitation, indicating that stimulation ...

In this episode, the Editors-in-Chief of the Journal of Neuroscience and eNeuro, Sabine Kastner and Christophe Bernard, discuss the importance of peer review and the progressive review models they have worked to implement at their respective journals. Both agree that, while imperfect, peer review is still a valuable part of the research process. Listen to their conversation to learn how their personal experiences as authors and reviewers shaped their decisions as editors. 

In this webinar, we will demystify MATLAB for new users and brush up on topics for those who are familiar with the program. We will take a step-by-step approach to learn how to develop algorithms, plot graphs for larger data sets, and perform data visualization and analysis.

Missense variants in O-GlcNAc transferase (OGT) result in OGT congenital disorder of glycosylation (OGT-CDG), an intellectual disability syndrome associated with O-GlcNAc dyshomeostasis and a range of neurodevelopmental defects. Inhibition of O-GlcNAcase (OGA), the enzyme responsible for removing protein O-GlcNAcylation, has been explored as a target for modulating brain O-GlcNAc homeostasis in neurodegenerative diseases and may also be a target for OGT-CDG. Here, we describe an OGT-CDG mouse line, studied in male mice, that exhibits microcephaly, motor deficits, and brain O-GlcNAc dyshomeostasis, closely mirroring patient symptoms. We genetically explored OGA as a target for OGT-CDG by crossing these mice with a line carrying catalytically inactive OGA. Encouragingly, this partially restored O-GlcNAc homeostasis in brain and blood as determined by Ogt/Oga mRNA ratio. These findings suggest that OGA inhibition can modulate enzymatic imbalance in OGT-CDG mice possessing microcephaly and motor deficits, and ...

Huntington’s disease (HD) is a hereditary neurodegenerative disease that typically presents during midlife and is characterized by a combination of motor, cognitive and psychiatric symptoms. HD is fatal and arises from a mutation in the huntingtin ( HTT ) gene, which results in decreased neuronal health followed by brain atrophy, with spiny projection neurons (SPNs) of the striatum being especially vulnerable to degeneration. HTT loss-of-function, caused by haploinsufficiency of the wild-type HTT gene (wt HTT ), is an important feature of HD pathophysiology that has previously been understudied compared to mutant HTT gain-of-function mechanisms. wtHTT is essential for nervous system development and functions as a scaffolding protein to support many vital cellular functions including axonal transport, autophagy and synaptic plasticity. Here, we examined the consequences of wtHTT deletion in the adult cortex and striatum by conditionally inactivating wtHTT in 2–4-month-old male and female Htt fl/fl mice. wtH...