Brain Research, 311 (1984) 87-96 87 Elsevier BRE 10338 Electrophysiological Properties of in vitro Hippocampal Pyramidal Cells From Normal and Staggerer Mutant Mice EMMANUEL FOURNIER* and FRANCIS CREPEL Unitd INSERM U 97, 2 Ter rue d'Aldsia, 75014 Paris (France) (Accepted February 28th, 1984) Key words: hippocampus - - calcium spikes - - staggerer mice - - afterpotentials - - potassium conductances Electrophysiological properties of intracellularly recorded CA1 pyramidal cells from normal and staggerer mice were compared by using hippocampal slices maintained in vitro. In staggerer mice, the passive membrane properties of these neurons as well as their syn- aptic potentials elicited by stratum radiatum stimulation were very similar to those observed in normal mice. In control and mutant mice and in standard Krebs solution, CA1 pyramidal cells mainly fired tetrodoxin (TFX)°sensitive fast spikes but could also generate slow spikes. In both groups, replacement of calcium (Ca) by barium (Ba) or introduction of TEA in the bathing medium prolonged the repolarization of the fast spikes and suppressed the brief spike afterhyperpolarization which normally followed them, thus suggesting that both events involve fast potassium conductances. Furthermore, in both groups of animals, TEA and Ba enhanced the slow spikes and induced the appearance of prolonged depolarizations. These slow events were TI'X-resistant and were abolished by the Ca chan- nel blockers cadmium or cobalt, thus suggesting that they are Ca-dependent. On the whole, the present results indicate that the stag- gerer mutation which yields marked abnormalities in the bioelectrical properties of cerebellar Purkinje cells has no such effect on CA1 pyramidal cells. INTRODUCTION It is now well established that the excitability of in- vertebrate and vertebrate neurons is dependent on several types of ionic conductances 1. In unicellular animals and in invertebrates, the genetic control of the development of these ionic channels has already been investigated to some extent by the use of point mutations selectively affecting a given class of ionic channels, as for instance sodium (Na) or potassium (K) conductances in DrosophilaX6,25, 43 and calcium (Ca) conductances in Parameciumlg. In vertebrate neurons, such a genetic dissection of membrane conductances had never been studied un- til recent work~O. 1~ established that cerebellar Pur- kinje cells, which can normally generate Ca spikes 21,22, selectively lack these regenerative re- sponses in homozygous staggerer (sg/sg) mutant mice, probably because of a direct effect of the muta- tion on these neurons. Therefore, the question arises tO determine to what extent the staggerer mutation may affect Ca-conductances in other classes of neu- rons in the central nervous system, even in the ab- sence of any other striking abnormalities. Indeed, previous anatomical observations 34,35 support the view that the impact of this point mutation is restrict- ed to the cerebellum, where, besides the abnormality mentioned before, marked morphological, electro- physiological and biochemical alterations are also ap- parentg,35,37,3s. Hippocampal pyramidal cells provide a suitable model for such studies since the presence of voltage- dependent Ca conductances in these neurons is now well documented in guinea pig 6,7,17.30,39,40,42. We have compared the electrophysiological properties of CA1 pyramidal cells in normal mice and in staggerer mutant mice, with special reference to their passive electrical properties, their synaptic inputs and their ionic conductances. As in the companion paper 12, this was achieved by studying the responses of intra- * Present address: Laboratoire de Physiologie, Facult6 de M6decine, Piti6 Salp&ri6re, 91 Bd. de l'H6pital, 75623 Paris Cedex 13, France. Correspondence: F. Crepel, Unit6 INSERM U97, 2 Ter rue d'Al6sia, 75014 Paris, France.