The Journal of Neuroscience, April 4, 2007, 27(14):3823-3838; doi:10.1523/JNEUROSCI.4719-06.2007
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Cellular/Molecular
T-Type and L-Type Ca2+ Conductances Define and Encode the Bimodal Firing Pattern of Vestibulocerebellar Unipolar Brush Cells
Marco A. Diana,1
Yo Otsu,1
Gilliane Maton,2
Thibault Collin,2
Mireille Chat,2 and
Stéphane Dieudonné1
1Laboratoire de Neurobiologie, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8544, Ecole Normale Supérieure, 75005 Paris, France, and 2Laboratoire de Physiologie Cérébrale, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8118, Université Paris 5, 75006 Paris, France
Correspondence should be addressed to Marco Alberto Diana, Laboratoire de Neurobiologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8544, Ecole Normale Supérieure, 46 rue d'Ulm, 75005 Paris, France. Email: mdiana{at}ens.fr
Cerebellar unipolar brush cells (UBCs) are glutamatergic interneurons that receive direct input from vestibular afferents in the form of a unique excitatory synapse on their dendritic brush. UBCs constitute independent relay lines for vestibular signals, and their inherent properties most likely determine how vestibular activity is encoded by the cerebellar cortex. We now demonstrate that UBCs are bimodal cells; they can either fire high-frequency bursts of action potentials when stimulated from hyperpolarized potentials or discharge tonically during sustained depolarizations. The two functional states can be triggered by physiological-like activity of the excitatory input and are encoded by distinct Ca2+-signaling systems. By combining complementary strategies, consisting of molecular and electrophysiological analysis and of ultrafast acousto-optical deflector-based two-photon imaging, we unraveled the identity and the subcellular localization of the Ca2+ conductances activating in each mode. Fast inactivating T-type Ca2+ channels produce low-threshold spikes, which trigger the high-frequency bursts and generate powerful Ca2+ transients in the brush and, to a much lesser extent, in the soma. The tonic firing mode is encoded by a signalization system principally composed of L-type channels. Ca2+ influx during tonic firing produces a linear representation of the spike rate of the cell in the form of a widespread and sustained Ca2+ concentration increase and regulates cellular excitability via BK potassium channels. The bimodal firing pattern of UBCs may underlie different coding strategies of the vestibular input by the cerebellum, thus likely increasing the computational power of this structure.
Key words: unipolar brush cells; UBC; vestibulocerebellum; AOD-based two-photon imaging; T-type channels; L-type channels
Received Oct. 30, 2006;
revised Feb. 6, 2007;
accepted Feb. 7, 2007.
Correspondence should be addressed to Marco Alberto Diana, Laboratoire de Neurobiologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8544, Ecole Normale Supérieure, 46 rue d'Ulm, 75005 Paris, France. Email: mdiana{at}ens.fr
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