BK Channels Are Required for Multisensory Plasticity in the Oculomotor System.

Neural circuits are endowed with several forms of intrinsic and synaptic plasticity that could contribute to adaptive changes in behavior, but circuit complexities have hindered linking specific cellular mechanisms with their behavioral consequences. Eye movements generated by simple brainstem circuits provide a means for relating cellular plasticity to behavioral gain control. Here we show that firing rate potentiation, a form of intrinsic plasticity mediated by reductions in BK-type calcium-activated potassium currents in spontaneously firing neurons, is engaged during optokinetic reflex compensation for inner ear dysfunction. Vestibular loss triggers transient increases in postsynaptic excitability, occlusion of firing rate potentiation, and reductions in BK currents in vestibular nucleus neurons. Concurrently, adaptive increases in visually evoked eye movements rapidly restore oculomotor function in wild-type mice but are profoundly impaired in BK channel-null mice. Activity-dependent regulation of intrinsic excitability may be a general mechanism for adaptive control of behavioral output in multisensory circuits.

Comparison of plasticity and development of mouse optokinetic and vestibulo-ocular reflexes suggests differential gain control mechanisms.

Image stability during self-motion is achieved via a combination of the optokinetic and vestibulo-ocular reflexes (OKR and VOR). To determine whether distinct neuronal mechanisms are used to calibrate eye movements driven by visual and vestibular signals, we examined the developmental maturation and adaptive plasticity of the OKR and VOR in mice. The combined performance of the OKR and VOR, measured with infrared video oculography, produces nearly perfect gaze stability both in adult mice and in juveniles (postnatal days 21-26). Analyses of the OKR and VOR in isolation, however, indicate that VOR gains in juveniles are lower than in adult mice, while OKR gains are higher, indicating that juveniles rely more strongly on vision to stabilize gaze than do adults. Adaptive plasticity in the mouse OKR and VOR could be induced by 30 min of visual-vestibular mismatch training. Examination of the effects of training on the OKR and VOR revealed differential mechanisms and persistence of adaptive plasticity. Increases in VOR gain induced by rotating mice in the opposite direction to the visual surround were short-lasting and were accompanied by long-lasting increases in OKR gain. In contrast, decreases in VOR gain induced by rotating mice in the same direction as the visual surround were persistent and were accompanied by long-lasting increases in OKR gain. Vestibular training had little effect on either the OKR or VOR, while visual training induced robust and long-lasting increases in the OKR but had no effect on the VOR. These data indicate that multiple mechanisms of plasticity operate over distinct time courses to optimize oculomotor performance in mice.