The Calcium-binding protein parvalbumin modulates the firing

5 The Reticular Thalamic Nucleus (RTN) of the mouse is characterized by an overwhelming majority of 6 GABAergic neurons receiving afferences from both the thalamus and the cerebral cortex and sending projections 7 mainly on thalamo-cortical neurons. The RTN neurons express high levels of the “slow Ca2+ buffer” parvalbu8 min (PV) and are characterized by low-threshold Ca2+ currents, IT. We performed extracellular recordings in 9 ketamine/xylazine anesthetized mice in the rostro-medial portion of the RTN. In the RTN of wildtype and PV 10 knockout (PVKO) mice we distinguished 4 types of neurons characterized on the basis of their firing pattern: 11 irregular firing (Type I), medium bursting (Type II), long bursting (Type III) and tonically firing (Type IV). 12 In comparison to wildtype mice, we observed in the PVKOs the medium bursting (Type II) more frequently 13 than the long bursting type and longer inter-spike intervals within the burst without affecting the number of 14 spikes. This suggests that PV may affect the firing properties of RTN neurons via a mechanism associated 15 with the kinetics of burst discharges. Cav3.2 channels, which mediate the IT currents, were more localized to 16 the somatic plasma membrane of RTN neurons in PVKO mice, whereas Cav3.3 expression was similar in both 17 genotypes. The immuno electron-microscopy analysis showed that Cav3.2 channels were localized at active 18 axo-somatic synapses, thus suggesting that the differential localization of Cav3.2 in the PVKOs may affect 19 bursting dynamics. Cross-correlation analysis of simultaneously recorded neurons from the same electrode tip 20 showed that about one third of the cell pairs tended to fire synchronously in both genotypes, independent of 21 PV expression. In summary, PV deficiency does not affect the functional connectivity between RTN neurons, 22 but affects the distribution of Cav3.2 channels and the dynamics of burst discharges of RTN cells, which in turn 23 regulate the activity in the thalamo-cortical circuit. 24 ∗All Authors contributed equally to this work. Address for reprint request and other correspondance: L. Albéri, Unit of Anatomy, University of Fribourg, Route Albert-Gockel 1, CH-1700 Fribourg, Switzerland (E-mail: [email protected]), A.E.P. Villa, Laboratory of Neuroheuristics, University of Lausanne, UNIL Dorigny-Internef 138.1, CH-1015 Lausanne, Switzerland (E-mail: [email protected]). 1 Articles in PresS. J Neurophysiol (March 13, 2013). doi:10.1152/jn.00375.2012 Copyright © 2013 by the American Physiological Society.