Analysis of Cx36 knockout does not support tenet that olivary gap junctions are required for complex spike synchronization and normal motor performance.
Electrotonic coupling by gap junctions between neurons in the inferior olive has been claimed to underly complex spike (CS) synchrony of Purkinje cells in the cerebellar cortex and thereby to play a role in the coordination of movements. Here, we investigated the motor performance of mice that lack connexin36 (Cx36), which appears necessary for functional olivary gap junctions. Cx36 null-mutants are not ataxic, they show a normal performance on the accelerating rotorod, and they have a regular walking pattern. In addition, they show normal compensatory eye movements during sinusoidal visual and/or vestibular stimulation. To find out whether the normal motor performance in mutants reflects normal CS activity or some compensatory mechanism downstream of the cerebellar cortex, we determined the CS firing rate, climbing-fiber pause, and degree of CS synchrony. None of these parameters in the mutants differed from those in wildtype littermates. Finally, we investigated whether the role of coupling becomes apparent under challenging conditions, such as during application of the tremorgenic drug harmaline, which specifically turns olivary neurons into an oscillatory state at a high frequency. In both the mutants and wildtypes this application induced tremors of a similar duration with similar peak frequencies and amplitudes. Thus surprisingly, the present data does not support the notion that electrotonic coupling by gap junctions underlies synchronization of olivary spike activity and that these gap junctions are essential for normal motor performance.
Kistler
W M
WM
Department of Neuroscience, Erasmus MC, University Medical Center Rotterdam, 3000DR Rotterdam, The Netherlands.
De Jeu
M T G
MT
Elgersma
Y
Y
Van Der Giessen
R S
RS
Hensbroek
R
R
Luo
C
C
Koekkoek
S K E
SK
Hoogenraad
C C
CC
Hamers
F P T
FP
Gueldenagel
M
M
Sohl
G
G
Willecke
K
K
De Zeeuw
C I
CI
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D017630:Connexins / Q000172:deficiency* / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D009847:Olivary Nucleus / Q000187:drug effects / Q000502:physiology*; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology*; D000097004:Gap Junction delta-2 Protein
D017630:Connexins; D005136:Eye Proteins; D000097004:Gap Junction delta-2 Protein