Role of olivary electrical coupling in cerebellar motor learning.
The level of electrotonic coupling in the inferior olive is extremely high, but its functional role in cerebellar motor control remains elusive. Here, we subjected mice that lack olivary coupling to paradigms that require learning-dependent timing. Cx36-deficient mice showed impaired timing of both locomotion and eye-blink responses that were conditioned to a tone. The latencies of their olivary spike activities in response to the unconditioned stimulus were significantly more variable than those in wild-types. Whole-cell recordings of olivary neurons in vivo showed that these differences in spike timing result at least in part from altered interactions with their subthreshold oscillations. These results, combined with analyses of olivary activities in computer simulations at both the cellular and systems level, suggest that electrotonic coupling among olivary neurons by gap junctions is essential for proper timing of their action potentials and thereby for learning-dependent timing in cerebellar motor control.
Van Der Giessen
Ruben S
RS
Department of Neuroscience, Erasmus MC, 3000 DR Rotterdam, The Netherlands.
Koekkoek
Sebastiaan K
SK
van Dorp
Stijn
S
De Gruijl
Jornt R
JR
Cupido
Alexander
A
Khosrovani
Sara
S
Dortland
Bjorn
B
Wellershaus
Kerstin
K
Degen
Joachim
J
Deuchars
Jim
J
Fuchs
Elke C
EC
Monyer
Hannah
H
Willecke
Klaus
K
De Jeu
Marcel T G
MT
De Zeeuw
Chris I
CI
D000161:Acoustic Stimulation / Q000009:adverse effects; D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001767:Blinking / Q000502:physiology; D002531:Cerebellum / Q000502:physiology*; D003198:Computer Simulation; D017630:Connexins / Q000172:deficiency; D017629:Gap Junctions / Q000502:physiology*; D007858:Learning / Q000502:physiology*; D008124:Locomotion / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D008959:Models, Neurological; D009474:Neurons / Q000502:physiology*; D009847:Olivary Nucleus / Q000166:cytology*; D018408:Patch-Clamp Techniques / Q000379:methods; D011930:Reaction Time / Q000502:physiology; D013997:Time Factors; D000097004:Gap Junction delta-2 Protein
D017630:Connexins; D000097004:Gap Junction delta-2 Protein