@article{pmid42399454,

title = {GATOR1 signaling defects promote astrocytic metabolic rewiring and excitatory neurotransmitter cycling},

author = {Imane Hadj-Aissa and Maéline Muller and Jorge Soliz and Chantelle F Sephton and Paul A Dutchak},

doi = {10.1038/s44319-026-00846-w},

issn = {1469-3178},

year  = {2026},

date = {2026-07-01},

journal = {EMBO Rep},

abstract = {GATOR1 is an evolutionarily-conserved negative regulator of mTORC1-dependent signal transduction with pathogenic mutations linked to epilepsy, infantile spasms, and autism spectrum disorders. While a biochemical role of GATOR1 in amino acid-signaling is established, its cell-type specific contributions within the brain remain poorly defined. Here, we show that loss of GATOR1 function in astrocytic cells disrupts mitochondrial metabolism, with a selective dysfunction of the electron transport chain Complex II leading to elevated reactive oxygen species (ROS) and redox imbalance. These changes are accompanied by compensatory increases in antioxidant regulatory systems including superoxide dismutase, but remain insufficient to ameliorate the increased ROS. GATOR1-deficient astrocytes show metabolic rewiring marked by enhanced expression of glutamate uptake and glutamine synthesis pathways that contribute to the glutamate-glutamine cycle governing neuronal glutamine availability and synaptic homeostasis. In vivo, GATOR1 deficiency results in progressive astrocytic reactivity, seizures, and a reduced lifespan. These findings demonstrate that GATOR1 function is critical to coordinate astrocytic mitochondrial activity and neurotransmitter cycling pathways, establishing a novel link between intracellular amino acid-signaling in astrocytes and excitatory neural network homeostasis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41702264,

title = {Ontogeny of rhythmic performances and contribution of motor and perceptual rhythmic preferences},

author = {Pier-Alexandre Rioux and Daniel Fortin-Guichard and Émilie Cloutier-Debaque and Simon Grondin},

doi = {10.1016/j.jecp.2026.106483},

issn = {1096-0457},

year  = {2026},

date = {2026-06-01},

journal = {J Exp Child Psychol},

volume = {266},

pages = {106483},

abstract = {According to the entrainment region hypothesis, the range of tempi with which individuals can synchronize broadens during childhood. This developmental change is accompanied by a slowing of rhythmic preferences, as covered by the preferred period hypothesis. The later hypothesis posits that both motor and perceptual rhythmic preferences slow down throughout childhood, reflecting an increase in the common period of endogenous oscillations. This study aimed to further investigate the development of an entrainment region through rhythmic production (counting) and perception (tempo discrimination), while assessing the related contributions of a preferred period (spontaneous motor tempo and perceptual preferred tempo) between childhood and young adulthood. The study (N = 70) included three groups of children (5-6, 8-9, and 11-12 years) and one group of young adults (21-30 years). The results show a change in rhythmic performances around 11-12-year-olds, depending on the task employed. Moreover, results indicate a significant effect of rhythmic context in tempo discrimination, suggesting that young children are sometimes better at discriminating tempo slower than their motor and perceptual rhythmic preferences. For both rhythmic production and perception, spontaneous motor tempo emerges as the strongest contributor to the models, reinforcing its validity as an index of the biological constraints associated with endogenous oscillation. In contrast, the opposite direction of age across models suggests distinct developmental trajectories for rhythmic production and perception, highlighting the influence of additional constraints beyond endogenous oscillation (e.g., cognitive).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{SchaanProfes2026,

title = {Autophagy Is Required for Dopaminergic Axon Development and Confers Their Responsiveness to Guidance Cues},

author = {Marcos Schaan Profes and Charles Gora and Flavie Lavoie-Cardinal and Armen Saghatelyan and Martin Lévesque},

doi = {10.1523/jneurosci.1224-25.2026},

issn = {1529-2401},

year  = {2026},

date = {2026-05-27},

journal = {J. Neurosci.},

volume = {46},

number = {21},

publisher = {Society for Neuroscience},

abstract = {Midbrain dopamine (mDA) neurons play a wide range of brain functions, but the molecular mechanisms driving the formation of mDA circuits remain largely unknown. Here, we show that autophagy, the main cellular recycling pathway, is present in the growth cones of developing mDA neurons, and its level changes dynamically in response to guidance cues. To characterize the role of autophagy in mDA axon growth and guidance, we knocked out essential autophagy genes (Atg12, Atg5) specifically in mDA neurons in mice of either sex. Autophagy-deficient mDA axons exhibit axonal swellings and reduced branching both in vitro and in vivo. Strikingly, deletion of autophagy-related genes completely blunted the response of mDA neurons to both chemorepulsive and chemoattractive guidance cues. Our data demonstrate that autophagy plays a central role in regulating mDA neuron development by orchestrating axonal growth and guidance.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41962851,

title = {Excessive inhibition in the medial prefrontal cortex contributes to cognitive susceptibility in aging},

author = {Iason Keramidis and Patrick Desrosiers and Andrée-Anne Verreault and Romain Sansonetti and Reza Hazrati and Antoine G Godin and Yves De Koninck},

doi = {10.1016/j.nbd.2026.107385},

issn = {1095-953X},

year  = {2026},

date = {2026-04-01},

journal = {Neurobiol Dis},

volume = {224},

pages = {107385},

abstract = {Aging is the most impactful risk factor for cognitive decline. The prefrontal cortex (PFC), a brain region essential for higher-order cognition, undergoes age-related synaptic alterations which are postulated to yield an excitation/inhibition imbalance within the PFC. Here, we assessed cognitive performance in young and aged mice using a battery of behavioral tests linked to PFC function. Behavioral variability within the aged cohort suggested structured heterogeneity in cognitive performance. Using a data-driven analytical framework integrating behavioral dimensionality reduction, consensus clustering, and spectral embedding we achieved robust and stable behavioral subgroup separation within the aged population. This approach revealed a subset of "cognitively susceptible" aged mice with pronounced memory and novelty-directed exploration deficits, distinct from both "resilient" aged mice and young controls. Unlike resilient aged mice, susceptible mice showed intact social preference. Susceptible aged mice exhibited elevated levels of the inhibitory synaptic proteins Gephyrin and VGAT in the PFC, a pattern absent in resilient aged mice. Notably, the increase in Gephyrin was accounted for by a higher density of inhibitory synapses, indicating a structural shift toward inhibition. Consistent with this mechanism, optogenetically enhancing inhibition in the PFC of young mice was sufficient to recapitulate the memory and novelty-exploration deficits observed in susceptible aged mice. Altogether, these findings implicate excessive prefrontal inhibition as a mechanistic substrate contributing to cognitive susceptibility in unsuccessful aging.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}