Present address: Institut de Radioprotection et Sûreté Nucléaire, Fontenay aux Roses 92262, France.
Cellular anatomy, physiology and epileptiform activity in the CA3 region of Dcx knockout mice: a neuronal lamination defect and its consequences
Article first published online: 17 JAN 2012
© 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd
European Journal of Neuroscience
Volume 35, Issue 2, pages 244–256, January 2012
How to Cite
Bazelot, M., Simonnet, J., Dinocourt, C., Bruel-Jungerman, E., Miles, R., Fricker, D. and Francis, F. (2012), Cellular anatomy, physiology and epileptiform activity in the CA3 region of Dcx knockout mice: a neuronal lamination defect and its consequences. European Journal of Neuroscience, 35: 244–256. doi: 10.1111/j.1460-9568.2011.07962.x
- Issue published online: 17 JAN 2012
- Article first published online: 17 JAN 2012
- Received 6 September 2011, revised 2 November 2011, accepted 10 November 2011
- CA3 region;
- lamination defect;
- migration disorder;
- synaptic targeting
We report data on the neuronal form, synaptic connectivity, neuronal excitability and epileptiform population activities generated by the hippocampus of animals with an inactivated doublecortin gene. The protein product of this gene affects neuronal migration during development. Human doublecortin (DCX) mutations are associated with lissencephaly, subcortical band heterotopia, and syndromes of intellectual disability and epilepsy. In Dcx−/Y mice, CA3 hippocampal pyramidal cells are abnormally laminated. The lamination defect was quantified by measuring the extent of the double, dispersed or single pyramidal cell layer in the CA3 region of Dcx−/Y mice. We investigated how this abnormal lamination affected two groups of synapses that normally innervate defined regions of the CA3 pyramidal cell membrane. Numbers of parvalbumin (PV)-containing interneurons, which contact peri-somatic sites, were not reduced in Dcx−/Y animals. Pyramidal cells in double, dispersed or single layers received PV-containing terminals. Excitatory mossy fibres which normally target proximal CA3 pyramidal cell apical dendrites apparently contact CA3 cells of both layers in Dcx−/Y animals but sometimes on basilar rather than apical dendrites. The dendritic form of pyramidal cells in Dcx−/Y animals was altered and pyramidal cells of both layers were more excitable than their counterparts in wild-type animals. Unitary inhibitory field events occurred at higher frequency in Dcx−/Y animals. These differences may contribute to a susceptibility to epileptiform activity: a modest increase in excitability induced both interictal and ictal-like discharges more effectively in tissue from Dcx−/Y mice than from wild-type animals.