title: Pentylenetetrazol-induced epileptiform activity affects basal synaptic transmission and short-term plasticity in monosynaptic connections.
abstract: Epileptic activity is generally induced in experimental models by local application of epileptogenic drugs, including pentylenetetrazol (PTZ), widely used on both vertebrate and invertebrate neurons. Despite the high prevalence of this neurological disorder and the extensive research on it, the cellular and molecular mechanisms underlying epileptogenesis still remain unclear. In this work, we examined PTZ-induced neuronal changes in Helix monosynaptic circuits formed in vitro, as a simpler experimental model to investigate the effects of epileptiform activity on both basal release and post-tetanic potentiation (PTP), a form of short-term plasticity. We observed a significant enhancement of basal synaptic strength, with kinetics resembling those of previously described use-dependent forms of plasticity, determined by changes in estimated quantal parameters, such as the readily releasable pool and the release probability. Moreover, these neurons exhibited a strong reduction in PTP expression and in its decay time constant, suggesting an impairment in the dynamic reorganization of synaptic vesicle pools following prolonged stimulation of synaptic transmission. In order to explain this imbalance, we determined whether epileptic activity is related to the phosphorylation level of synapsin, which is known to modulate synaptic plasticity. Using western blot and immunocytochemical staining we found a PTZ-dependent increase in synapsin phosphorylation at both PKA/CaMKI/IV and MAPK/Erk sites, both of which are important for modulating synaptic plasticity. Taken together, our findings suggest that prolonged epileptiform activity leads to an increase in the synapsin phosphorylation status, thereby contributing to an alteration of synaptic strength in both basal condition and tetanus-induced potentiation.
authors: Section of Physiology, Department of Neuroscience, University of Turin, Turin, Italy. carlo.giachello@unito.it
authors: Carlo Natale Giuseppe
authors: CN
authors: Giachello
authors: Federica
authors: F
authors: Premoselli
authors: Pier Giorgio
authors: PG
authors: Montarolo
authors: Mirella
authors: M
authors: Ghirardi
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D018920:Coculture Techniques; D004827:Epilepsy / Q000139:chemically induced* / Q000503:physiopathology*; D006372:Helix, Snails; D006801:Humans; D009473:Neuronal Plasticity; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D010433:Pentylenetetrazole / Q000009:adverse effects*; D010766:Phosphorylation; D016704:Synapsins / Q000378:metabolism; D055366:Synaptic Potentials / Q000187:drug effects; D009435:Synaptic Transmission
chemical_list: D016704:Synapsins; D010433:Pentylenetetrazole