Inactivation of calcium-binding protein genes induces 160 Hz oscillations in the cerebellar cortex of alert mice.
Oscillations in neuronal populations may either be imposed by intrinsically oscillating pacemakers neurons or emerge from specific attributes of a distributed network of connected neurons. Calretinin and calbindin are two calcium-binding proteins involved in the shaping of intraneuronal Ca2+ fluxes. However, although their physiological function has been studied extensively at the level of a single neuron, little is known about their role at the network level. Here we found that null mutations of genes encoding calretinin or calbindin induce 160 Hz local field potential oscillations in the cerebellar cortex of alert mice. These oscillations reached maximum amplitude just beneath the Purkinje cell bodies and are reinforced in the cerebellum of mice deficient in both calretinin and calbindin. Purkinje cells fired simple spikes phase locked to the oscillations and synchronized along the parallel fiber axis. The oscillations reversibly disappeared when gap junctions or either GABA(A) or NMDA receptors were blocked. Cutaneous stimulation of the whisker region transiently suppressed the oscillations. However, the intrinsic somatic excitability of Purkinje cells recorded in slice preparation was not significantly altered in mutant mice. Functionally, these results suggest that 160 Hz oscillation emerges from a network mechanism combining synchronization of Purkinje cell assemblies through parallel fiber excitation and the network of coupled interneurons of the molecular layer. These findings demonstrate that subtle genetically induced modifications of Ca2+ homeostasis in specific neuron types can alter the observed dynamics of the global network.
Cheron
Guy
G
Laboratory of Electrophysiology, Université Mons-Hainaut, 7000 Mons, Belgium. guy.cheron@umh.ac.be
Gall
David
D
Servais
Laurent
L
Dan
Bernard
B
Maex
Reinoud
R
Schiffmann
Serge N
SN
D000200:Action Potentials; D000818:Animals; D001288:Attention; D064032:Calbindin 2; D064026:Calbindins; D002462:Cell Membrane / Q000502:physiology; D002525:Cerebellar Cortex / Q000166:cytology / Q000502:physiology*; D004553:Electric Conductivity; D019054:Evoked Potentials, Motor; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009415:Nerve Net / Q000502:physiology; D018408:Patch-Clamp Techniques; D010507:Periodicity; D011689:Purkinje Cells / Q000502:physiology*; D064030:S100 Calcium Binding Protein G / Q000235:genetics / Q000502:physiology*
C576511:Calb2 protein, mouse; D064032:Calbindin 2; D064026:Calbindins; D064030:S100 Calcium Binding Protein G