| || |
|Title:||INTRINSIC AND SYNAPTIC RESPONSES OF PYRAMIDAL NEURONS AND INTERNEURONS IN IONIC CONDITIONS CORRESPONDING TO PAROXYSMAL STATES IN VITRO|
| || |
|Authors/Affiliations:||1 Josée Seigneur*; 1 Igor Timofeev; |
1 Centre de recherche Université Laval Robert-Giffard, Québec, QC, Canada
| || |
|Content:||Cortically generated seizures are composed of spike-wave complexes and runs of paroxysmal fast spikes. The seizures are associated with a reduction of [ Ca2+]o, an increase of [K+]o, and accompanied by a decrease of synaptic efficacy. Previous studies have shown that during these seizures in vivo intrinsic excitability of regular-spiking pyramidal neuron is reduced while the intrinsic excitability of fast-spiking interneuron enhanced ( Timofeev et al. 2002). The synaptic responsiveness decreased during seizure remains decreased for minutes after the end of seizures (Nita et al. 2007). Objectives: Here we studied the hypothesis that ionic change accompanying seizures is sufficient to induce alterations of synaptic ant intrinsic responses and its alteration could be different in excitatory and inhibitory cells. Methods: We investigated the influence of [Ca+2]o and [K+]o alterations on intrinsic and synaptic responses in rat cortical slices. We recorded fast-spiking (FS) interneurons and regular-spiking (RS) pyramidal neurons in normal and paroxysmal ionic conditions with a diminution of [ Ca2+]o from 1.2 mM to 0.6 mM and an increase of [K+]o from 2.8 mM to 12 mM in extracellular milieu. Synaptic activation was achieved using minimal cortical electrical stimulation. Intrinsic excitability was tested using intracellularly applied current pulses. Results: The intrinsic responses to ionic conditions are different in RS than in FS neurons. When [ Ca2+]o was decreased to 0.6 mM and the [K+]o and the [ Mg2+]o were maintained respectively to 6.25 mM and 0.5 mM, the membrane potential ( Vm) was depolarized close to the firing threshold (-55.67± 2.50 mV, RS, -53.06 ± 2.52 mV, FS). Independently from [ Ca2+]o and [Mg+2]o concentration, [K+]o elevation to 6.25 mM, induced spiking in 1/3 (5/9 FS, 10/36 RS) of the total 45 neurons recorded while 2/3 (4/9 FS, 26/36 RS) didn't reach the firing threshold. In pathological ACSF solution corresponding to sever seizures ( Ca2+ 0.6 mM, K+ 12 mM, Mg2+ 0.5 mM), the mean Vm was suprathreshold (-37.25 ± 5.86 mV, RS, -39.54 ± 4.64 mV, FS). 75% of FS neurons continue to spike but only a minority of RS could generate spikes in the first 5 min in this condition. In these ionic conditions, the input resistance of neurons decreases more dramatically in regular-spiking than in fast-spiking neurons. The synaptic responses were greatly reduced in both types of neurons in the same ionic conditions. We demonstrate a block of axonal spike propagation [K+]o in 12 mM. Conclusion: We conclude that ionic changes accompanying seizures could explain alteration in intrinsic and synaptic responsiveness. We suggest that chemical synaptic transmission does not play a critical role in synchronization during seizures. |
Supported by CHIR and NSREC.
Nita, D.A., Cisse, Y., and Timofeev, I. (2007). Epilepsia.
Timofeev, I., Grenier, F., and Steriade, M. (2002). Neuroscience 114, 1115-1132.
| || |