Pentylenetetrazol-Induced Epileptiform Activity Affects Basal Synaptic Transmission and Short-Term Plasticity in Monosynaptic Connections

Giachello, Carlo Natale Giuseppe; Premoselli, Federica; Montarolo, Pier Giorgio; Ghirardi, Mirella
February 2013
PLoS ONE;Feb2013, Vol. 8 Issue 2, p1
Academic Journal
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.


Related Articles

  • Emergence of Connectivity Motifs in Networks of Model Neurons with Short- and Long-Term Plastic Synapses. Vasilaki, Eleni; Giugliano, Michele // PLoS ONE;Jan2014, Vol. 9 Issue 1, p1 

    Recent experimental data from the rodent cerebral cortex and olfactory bulb indicate that specific connectivity motifs are correlated with short-term dynamics of excitatory synaptic transmission. It was observed that neurons with short-term facilitating synapses form predominantly reciprocal...

  • Behavioural genetics: Taming of the vole. Rowan, Alison // Nature Reviews Neuroscience;Aug2004, Vol. 5 Issue 8, p596 

    Examines the influence of expressed single gene, V1aR on the behavior of voles. Characteristics of voles; Role of vasopressin and dopamine in the regulation of attachment between animals; Activation of the recognition pathways.

  • AMPA receptors regulate transcription of the plasticity-related immediate-early gene Arc. Rao, Vikram R.; Pintchovski, Sean A.; Chin, Jeannie; Peebles, Carol L.; Mitra, Siddhartha; Finkbeiner, Steven // Nature Neuroscience;Jul2006, Vol. 9 Issue 7, p887 

    Learning and memory depend critically on long-term synaptic plasticity, which requires neuronal gene expression. In the prevailing view, AMPA receptors mediate fast excitatory synaptic transmission and effect short-term plasticity, but they do not directly regulate neuronal gene expression. By...

  • Developing velocity sensitivity in a model neuron by local synaptic plasticity. Tamosiunaite, Minija; Porr, Bernd; W�rg�tter, Florentin // Biological Cybernetics;May2007, Vol. 96 Issue 5, p507 

    Sensor neurons, like those in the visual cortex, display specific functional properties, e.g., tuning for the orientation, direction and velocity of a moving stimulus. It is still unclear how these properties arise from the processing of the inputs which converge at a given cell. Specifically,...

  • Self-administration enhances excitatory synaptic transmission in the bed nucleus of the stria terminalis. Dumont, Eric C; Mark, Gregory P; Mader, Sarah; Williams, John T // Nature Neuroscience;Apr2005, Vol. 8 Issue 4, p413 

    Understanding the neurobiology of motivation might help in reducing compulsive behaviors such as drug addiction or eating disorders. This study shows that excitatory synaptic transmission was enhanced in the bed nucleus of the stria terminalis of rats that performed an operant task to obtain...

  • TARP γ-8 controls hippocampal AMPA receptor number, distribution and synaptic plasticity. Rouach, Nathalie; Byrd, Keith; Petralia, Ronald S.; Elias, Guillermo M.; Adesnik, Hillel; Tomita, Susumu; Karimzadegan, Siavash; Kealey, Colin; Bredt, David S.; Nicoll, Roger A. // Nature Neuroscience;Nov2005, Vol. 8 Issue 11, p1525 

    Synaptic plasticity involves activity-dependent trafficking of AMPA-type glutamate receptors. Numerous cytoplasmic scaffolding proteins are postulated to control AMPA receptor trafficking, but the detailed mechanisms remain unclear. Here, we show that the transmembrane AMPA receptor regulatory...

  • Inhibitory synapses turn exciting. Kauer, Julie A. // Nature Neuroscience;Mar2005, Vol. 8 Issue 3, p257 

    Examines how activity-dependent synaptic plasticity shapes the development of inhibitory synapses. Demonstration that inhibitory synapses transiently co-release glutamate in the developing rat auditory system; Importance of activation of postsynaptic NMDA receptors for the plasticity mechanisms;...

  • Stably maintained dendritic spines are associated with lifelong memories. Guang Yang; Feng Pan; Wen-Biao Gan // Nature;12/17/2009, Vol. 462 Issue 7275, p920 

    Changes in synaptic connections are considered essential for learning and memory formation. However, it is unknown how neural circuits undergo continuous synaptic changes during learning while maintaining lifelong memories. Here we show, by following postsynaptic dendritic spines over time in...

  • Transmission Efficacy and Plasticity in Glutamatergic Synapses Formed by Excitatory Interneurons of the Substantia Gelatinosa in the Rat Spinal Cord.  // PLoS ONE;2009, Vol. 4 Issue 11, p1 

    The article presents a study which examines the mechanism involved in the functional organization and properties of excitatory synapses formed by Substantia gelatinosa (SG) excitatory interneurons (EINs). It is said that most unmyelinated primary afferents conclude and the central nociceptive...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics