Evaluation of ultrastructural correlates for neuronal membrane remodeling during TTX-induced synaptic plasticity

Synaptic plasticity is a fundamental process underlying learning and memory, modulating neuronal connectivity through complex mechanisms that include neuronal membrane remodeling. This study investigates the ultrastructural correlates of membrane homeostasis during tetrodotoxin (TTX)-induced synaptic plasticity in murine entorhino-hippocampal tissue cultures. Using transmission electron microscopy, we aimed to: (1) analyze presynaptic vesicles to evaluate presynaptic targets of TTX-induced plasticity, (2) evaluate multivesicular and lamellar bodies after activity deprivation in different neuronal compartments of both dentate granule cells and CA1 pyramidal neurons, and (3) assess the role of astrocytic lipid droplets as a major resource for neuronal membrane remodeling. Our findings reveal significant alterations in the ultrastructure of both pre- and postsynaptic sites, indicating activity-dependent changes in synaptic resources. Additionally, changes in astrocytic lipid droplets upon activity deprivation suggest the involvement of astrocyte-neuron lipid transport mechanism supporting membrane homeostasis during synaptic plasticity. These results underscore the complexity of neuronal membrane remodeling and highlight the importance of lipid metabolism in sustaining synaptic function and plasticity.