Numerous studies in rodents have shown that the functional efficacy of several neurotransmitter receptors and the intrinsic membrane excitability of central vestibular neurons, as well as the organization of synaptic connections within and between vestibular nuclei can be modified during postnatal development, after a lesion of peripheral vestibular organs or in vestibular-deficient mutant animals. This review mainly focuses on the intrinsic membrane properties of neurons of the medial vestibular nuclei of rodents, their postnatal maturation, and changes following experimental or congenital alterations in vestibular inputs. It also presents the concomitant modifications in the distribution of these neurons into different neuron types, which has been based on their membrane properties in relation to their anatomical, biochemical, or functional properties. The main points discussed in this review are that (1) the intrinsic membrane properties can be used to distinguish between two dominant types of neurons, (2) the system remains plastic throughout the whole life of the animal, and finally, (3) the intracellular calcium concentration has a major effect on the intrinsic membrane properties of central vestibular neurons.

The nonlinear properties of the dendrites in prepositus hypoglossi neurons are involved in maintenance of eye position. The biophysical properties of these neurons are essential for the operation of the vestibular neural integrator that converts a head velocity signal to one that controls eye position. A novel method named QSA (quadratic sinusoidal analysis) for voltage clamped neurons was used to quantify nonlinear responses that are dominated by dendrites. The voltage clamp currents were measured at harmonic and interactive frequencies using specific stimulation frequencies, which act as frequency probes of the intrinsic nonlinear neuronal behavior. These responses to paired frequencies form a matrix that can be reduced by eigendecomposition to provide a very compact piecewise quadratic analysis at different membrane potentials that otherwise is usually described by complex differential equations involving a large numbers of parameters and dendritic compartments. Moreover, the QSA matrix can be interpolated to capture most of the nonlinear neuronal behavior like a Volterra kernel. The interpolated quadratic functions of the two major prepositus hypoglossi neurons, namely type B and D, are strikingly different. A major part of the nonlinear responses is due to the persistent sodium conductance, which appears to be essential for sustained nonlinear effects induced by NMDA activation and thus would be critical for the operation of the neural integrator. Finally, the dominance of the nonlinear responses by the dendrites supports the hypothesis that persistent sodium conductance channels and NMDA receptors act synergistically to dynamically control the influence of individual synaptic inputs on network behavior.

The effect of the lack of vestibular input on the membrane properties of central vestibular neurons was studied by using a strain of transgenic, vestibular-deficient mutant KCNE1(-/-) mice where the hair cells of the inner ear degenerate just after birth. Despite the absence of sensory vestibular input, their central vestibular pathways are intact. Juvenile and adult homozygous mutant have a normal resting posture, but show a constant head bobbing behaviour and display the shaker/waltzer phenotype characterized by rapid bilateral circling during locomotion. In juvenile mice, the KCNE1 mutation was associated with a strong decrease in the expression of the calcium-binding proteins calbindin, calretinin and parvalbumin within the medial vestibular nucleus (MVN) and important modifications of the membrane properties of MVN neurons. In adult mice, however, there was almost no difference between the membrane properties of MVN neurons of homozygous and control or heterozygous mutant mice, which have normal inner ear hair cells and show no behavioural symptoms. The expression levels of calbindin and calretinin were lower in adult homozygous mutant animals, but the amount of calcium-binding proteins expressed in the MVN was much greater than in juvenile mice. These data demonstrate that suppression of sensory vestibular inputs during a 'sensitive period' around birth can generate the circling/waltzing behaviour, but that this behaviour is not due to persistent abnormalities of the membrane properties of central vestibular neurons. Altogether, maturation of the membrane properties of central vestibular neurons is delayed, but not impaired by the absence of sensory vestibular information.

Numerous models of the oculomotor neuronal integrator located in the prepositus hypoglossi nucleus (PHN) involve both highly tuned recurrent networks and intrinsic neuronal properties; however, there is little experimental evidence for the relative role of these two mechanisms. The experiments reported here show that all PHN neurons (PHNn) show marked phasic behavior, which is highly oscillatory in approximately 25% of the population. The behavior of this subset of PHNn, referred to as type D PHNn, is clearly different from that of the medial vestibular nucleus neurons, which transmit the bulk of head velocity-related sensory vestibular inputs without integrating them. We have investigated the firing and biophysical properties of PHNn and developed data-based realistic neuronal models to quantitatively illustrate that their active conductances can produce the oscillatory behavior. Although some individual type D PHNn are able to show some features of mathematical integration, the lack of robustness of this behavior strongly suggests that additional network interactions, likely involving all types of PHNn, are essential for the neuronal integrator. Furthermore, the relationship between the impulse activity and membrane potential of type D PHNn is highly nonlinear and frequency-dependent, even for relatively small-amplitude responses. These results suggest that some of the synaptic input to type D PHNn is likely to evoke oscillatory responses that will be nonlinearly amplified as the spike discharge rate increases. It would appear that the PHNn have specific intrinsic properties that, in conjunction with network interconnections, enhance the persistent neural activity needed for their function.

Central vestibular neurons play an important role in the processing of body motion-related multisensory signals and their transformation into motor commands for gaze and posture control. Over recent years, medial vestibular nucleus (MVN) neurons and to a lesser extent other vestibular neurons have been extensively studied in vivo and in vitro, in a range of species. These studies have begun to reveal how their intrinsic electrophysiological properties may relate to their response patterns, discharge dynamics and computational capabilities. In vitro studies indicate that MVN neurons are of two major subtypes (A and B), which differ in their spike shape and after-hyperpolarizations. This reflects differences in particular K+ conductances present in the two subtypes, which also affect their response dynamics with type A cells having relatively low-frequency dynamics (resembling “tonic” MVN cells in vivo) and type B cells having relatively high-frequency dynamics (resembling “kinetic” cells in vivo). The presence of more than one functional subtype of vestibular neuron seems to be a ubiquitous feature since vestibular neurons in the chick and frog also subdivide into populations with different, analogous electrophysiological properties. The ratio of type A to type B neurons appears to be plastic, and may be determined by the signal processing requirements of the vestibular system, which are species-variant. The membrane properties and discharge pattern of type A and type B MVN neurons develop largely post-natally, through the expression of the underlying ion channel conductances. The membrane properties of MVN neurons show rapid and long-lasting plastic changes after deafferentation (unilateral labyrinthectomy), which may serve to maintain their level of activity and excitability after the loss of afferent inputs.

Gaze and postural stabilization is the result of a complex multisensory integration, which can be defined as the process of matching multiple internal representations of an external event (head and/or trunk rotation), obtained from different sensory modalities, into a unique intrinsic frame of reference in which appropriate motor commands can be coded. Despite the importance of the labyrinths, their lesions are not rare. They result in static and dynamic deficits. What is remarkable is that some of these deficits recover in mammalian species, including humans: the vestibular compensation process refers to the complete or partial normalization of the static and dynamic postural and ocular motor deficits. In the following, only two aspects of vestibular compensation will be discussed: (1) the relationship between the recovery of the vestibulo-ocular reflexes and the postlesional plasticity of the intrinsic membrane properties of the medial vestibular nucleus, and (2) the relationship between the postural recovery and the vestibular control of the skeletal geometry at large. Subsequently, the results of investigations in animal models will be related to some clinical findings. While such an exercise is highly speculative, it points to new directions for clinical research and vestibular rehabilitation.

Methods for determining empirical linear transfer functions of experimentally obtained or model vestibular neurons from the modulation of their discharge firing rate by current input have been developed and shown to distinguish between regularly firing neurons with prominent after hyperpolarizations, AHP (Type A), and cells with more complex AHP's (Type B). An increase in magnitude of the modulated spike discharge rate with frequency has been observed to be greater in Type B compared to Type A neurons. In order to better interpret this finding, simulations of spike frequency modulation were done with known Hodgkin-Huxley type neuronal models consisting of non-linear differential equations that show the essential behavior of vestibular neurons, namely previously published Type A and B neuronal models (AvRon and Vidal, 1999). An empirical spike rate transfer function was obtained from the analysis of the spike rate modulation at different stimulating sinusoidal frequencies, and was compared with the theoretical linear transfer function obtained from the exact linearized equations and type B neuronal models. These linearized theoretical frequency domain functions reveal the underlying voltage dependent conductances by showing resonant behavior, increased impedance with activation of negative conductances and specific kinetic responses dependent on the time constants of the active conductances. It is shown that the theoretical linear transfer functions can be approximated by empirical spike rate transfer functions, which indicates that the basic strategy of this analysis can be applied to data from real neurons. The simulations demonstrate that such an approach is a valid experimental method that allows one to estimate membrane properties from frequency modulation of discharge rates measured extracellularly.