Increased excitation and decreased inhibition associated with abnormal neuronal morphology, aberrant ion channel properties, and synaptic dysfunction contribute to hyperexcitability in Alzheimer’s disease hiPSC-derived neuronal cultures and cerebral organoids.
Impaired GABAergic and glutamatergic synaptic function and loss of interneurons in the amygdala, hippocampus, and cerebellum cause characteristic disease symptoms in a mouse model juvenile neuronal ceroid lipofuscinosis.
M2 cortex-dorsolateral striatum circuit is functionally altered in Huntington's disease and, by boosting its activity, we reverse symptoms at behavioral, physiological, and morphological level in symptomatic mice.
In mouse models of Huntington's disease, the subthalamic nucleus, which suppresses movements, also exhibits impaired glutamate homeostasis, NMDA receptor-dependent mitochondrial oxidant stress, firing disruption, and 30% neuronal loss.
Vps29 promotes retromer localization in the adult Drosophila brain, engaging Rab7 and TBC1D5, and its loss triggers age-dependent neuronal impairments in endolysosomal trafficking and synaptic transmission.
Two genetically distinct Stxbp1 haploinsufficiency mouse models exhibit seizures and impairments in cognitive, psychiatric, and motor functions, representing robust preclinical models of STXBP1 encephalopathy with both construct and face validity.
Super-resolution imaging reveals that the microtubule-associated protein Tau regulates the Fyn kinase organisation in dendrites, and that the frontotemporal dementia mutant Tau promotes aberrant Fyn clustering, potentially leading to synaptic dysfunction.