Phase-Dependent Response to Electrical Stimulation of Cortical Networks during Recurrent Epileptiform Short Discharge Generation In Vitro.

The closed-loop control of pathological brain activity is a challenging task. In this study, we investigated the sensitivity of continuous epileptiform short discharge generation to electrical stimulation applied at different phases between the discharges using an in vitro 4-AP-based model of epilepsy in rat hippocampal slices. As a measure of stimulation effectiveness, we introduced a sensitivity function, which we then measured in experiments and analyzed with different biophysical and abstract mathematical models, namely, (i) the two-order subsystem of our previous Epileptor-2 model, describing short discharge generation governed by synaptic resource dynamics; (ii) a similar model governed by shunting conductance dynamics (Epileptor-2B); (iii) the stochastic leaky integrate-and-fire (LIF)-like model applied for the network; (iv) the LIF model with potassium M-channels (LIF+KM), belonging to Class II of excitability; and (v) the Epileptor-2B model with after-spike depolarization. A semi-analytic method was proposed for calculating the interspike interval (ISI) distribution and the sensitivity function in LIF and LIF+KM models, which provided parametric analysis. Sensitivity was found to increase with phase for all models except the last one. The Epileptor-2B model is favored over other models for subthreshold oscillations in the presence of large noise, based on the comparison of ISI statistics and sensitivity functions with experimental data. This study also emphasizes the stochastic nature of epileptiform discharge generation and the greater effectiveness of closed-loop stimulation in later phases of ISIs.

Prenatal hypoxia produces memory deficits associated with impairment of long-term synaptic plasticity in young rats.

Prenatal hypoxia often results in dramatic alterations in developmental profiles and behavioral characteristics, including learning and memory, in later life. Despite the accumulation of considerable amounts of experimental data, the mechanisms underlying developmental deficits caused by prenatal hypoxia remain unclear. In the present study, we investigated whether prenatal hypoxia on embryonic day 14 (E14) affected synaptic properties in the hippocampus and hippocampal-related cognitive functions in young rats. We found that 20- to 30-d-old rats subjected to prenatal hypoxia had significantly disturbed basal synaptic transmission in CA3-CA1 synapses and a two-fold decrease in hippocampal long-term synaptic potentiation. These alterations were accompanied by a significant decline in the protein level of GluN2B but not GluN2A NMDA receptor subunits. In addition, the number of synaptopodin-positive dendritic spines in the CA1 area of the hippocampus was reduced in the rats exposed to prenatal hypoxia. These changes resulted in significant learning and memory deficits in a novel object recognition test.