Information about head movement and orientation, from the semicircular canals and otolith organs of the inner ear, is essential for the normal control of eye movements, gaze and body posture, as well as cognitive orientation and spatial navigation. Increasingly it also appears that vestibular sensory inputs play an important role in the early postnatal development of normal motor control. Thus, in human infants with congenital lack of labyrinthine function there is a marked slowing of motor development (Kaga, 1999), while many mouse mutants with inner ear deformities show a characteristic, life-long head bobbing and rapid circling behaviour (the shaker/waltzer phenotype; Rabbath et al. 2001; Vidal et al. 2004). The role of vestibular inputs in shaping the early development of motor systems is largely unexplored. In this volume of The Journal of Physiology, Eugène et al. (2007) show that vestibular information may have an essential, formative role in the development of the motor system at an early age. Eugène et al. (2007) exploited a transgenic mouse strain with a null mutation of the KCNE1 gene, encoding the IsK channel protein, which causes a complete loss of sensory hair cells in the inner ears soon after birth (Vetter et al. 1996, Vidal et al. 2004). The KCNE1−/− animal shows characteristic signs of severe vestibular loss as early as postnatal day 7 (head bobbing, circling, inability to swim, difficulty in righting). Since KCNE1 is not expressed in the brain, this mutant provides a useful model in which the peripheral sensory receptors degenerate while the central vestibular pathways, presumably, are normal. In a previous behavioural analysis also published in The Journal of Physiology, Vidal et al. (2004) showed that the resting posture of the KCNE1−/− mouse was normal, but its locomotion was characterized by circling episodes to either side, so that the mutant animal could not walk in a straight line. Thus, proprioceptive inputs may help compensate for the lack of vestibular feedback in the regulation of posture, but the vestibular system appears to be essential for normal walking. In the current study, Eugène et al. (2007) analysed in detail the intrinsic membrane and firing properties of neurons in the medial vestibular nucleus (MVN) of the KCNE1−/− mouse. Remarkably, in the adult mutant mouse the membrane properties and firing rates of MVN neurons are very similar to normal. The head bobbing and waltzing behaviour is therefore not due to deficits at the level of the brainstem vestibular networks. Instead, the KCNE1−/− animal is equivalent to a bilaterally labyrinthectomised, normal animal – it receives no afferent inputs from the two inner ears, and its vestibular neurons are essentially normal. Crucially, however, much previous research has shown that bilateral labyrinthectomy in adult, normal animals never induces the characteristic head bobbing and waltzing behaviour seen in the mutant. Eugène et al. therefore conclude that the head instability and waltzing behaviour is precipitated only if the vestibular information is absent at some critical, early stage in postnatal life. Perhaps the vestibular signals relating to gravity, orientation and self-motion are essential for the correct postnatal maturation of forebrain motor circuits, particularly in the basal ganglia. Disorders of motor function may therefore result either from a congenital lack of vestibular information during this critical period, as observed in many mouse mutant strains with inner ear malformations, or alternatively in mutants where the inner ears are normal, because of basal ganglia deficits that prevent this information being correctly used. Further studies of the effects of early vestibular deprivation on motor development in the mouse, and the identification of their human equivalents, promise to be interesting.
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Sep 29, 2011
Harprit Kaur + 1
Open Access