Models of utricular bouton afferents: role of afferent-hair cell connectivity in determining spike train regularity

Abstract

Vestibular bouton afferent terminals in turtle utricle can be categorized into four types depending on their location and terminal arbor structure: lateral extrastriolar (LES), striolar, juxtastriolar, and medial extrastriolar (MES). The terminal arbors of these afferents differ in surface area, total length, collecting area, number of boutons, number of bouton contacts per hair cell, and axon diameter (Huwe JA, Logan CJ, Williams B, Rowe MH, Peterson EH. 113: 2420-2433, 2015). To understand how differences in terminal morphology and the resulting hair cell inputs might affect afferent response properties, we modeled representative afferents from each region, using reconstructed bouton afferents. Collecting area and hair cell density were used to estimate hair cell-to-afferent convergence. Nonmorphological features were held constant to isolate effects of afferent structure and connectivity. The models suggest that all four bouton afferent types are electrotonically compact and that excitatory postsynaptic potentials are two to four times larger in MES afferents than in other afferents, making MES afferents more responsive to low input levels. The models also predict that MES and LES terminal structures permit higher spontaneous firing rates than those in striola and juxtastriola. We found that differences in spike train regularity are not a consequence of differences in peripheral terminal structure, per se, but that a higher proportion of multiple contacts between afferents and individual hair cells increases afferent firing irregularity. The prediction that afferents having primarily one bouton contact per hair cell will fire more regularly than afferents making multiple bouton contacts per hair cell has implications for spike train regularity in dimorphic and calyx afferents. Bouton afferents in different regions of turtle utricle have very different morphologies and afferent-hair cell connectivities. Highly detailed computational modeling provides insights into how morphology impacts excitability and also reveals a new explanation for spike train irregularity based on relative numbers of multiple bouton contacts per hair cell. This mechanism is independent of other proposed mechanisms for spike train irregularity based on ionic conductances and can explain irregularity in dimorphic units and calyx endings.

Cholinergic Modulation of Membrane Properties of Calyx Terminals in the Vestibular Periphery

“…Most afferents have 'dimorphic' terminals and receive inputs from both type I and type II hair cells [1]. Irregular dimorphic afferents have fewer bouton terminals than regular dimorphic afferents [4,5], suggesting that the ratio of calyx-to-bouton terminals affects afferent properties. Note that some of the input to dimorphic afferents could come from type II hair cells by direct synapses on the outer surface of calyces [3,77].…”

“…In the present study, we only recorded from calyces in the central regions of the cristae and cannot speculate about the effects on calyces that innervate the peripheral regions. Afferents that innervate the central region have the most irregular resting discharge [1], receive inputs only from calyx terminals or have fewer bouton terminals compared to peripheral regular dimorphic afferents [4,5], show the largest efferent-mediated effects [11][12][13]54], and have an abundance of KCNQ channels [31].…”

“…The firing regularity of these 'dimorphic' afferents is correlated with the number of bouton terminals: those with fewer bouton terminals have higher irregular resting discharges [4,5].…”

Efferent Inputs Are Required for Normal Function of Vestibular Nerve Afferents

“…Because the net effect of efferents on Type II hair cells/bouton terminals is small, efferent-mediated changes in dimorphic fibers are likely to be dominated by calyx terminals. It has been shown that irregular dimorphic afferents have fewer bouton terminals than regular dimorphic afferents (Goldberg et al, 1990a;Holmes et al, 2017) and are therefore expected to show more robust responses to efferent inputs than regular dimorphic afferents. This is consistent with the inhibition of afferents as a function of CV* observed in the present study.…”

Enhanced Activation of HCN Channels Reduces Excitability and Spike-Timing Regularity in Maturing Vestibular Afferent Neurons

“…In addition to ion channels, models have shown that the size and rate of synaptic events also shapes spike-timing statistics. For example, turtle vestibular neurons having small compact terminal arbors with bouton synapses on few hair cells might produce large and temporally brief synaptic events whereas neurons with extended arbors containing hundreds of bouton-like terminals on many spatially dispersed hair cells may produce small but rapidly arriving events (Goldberg and Holt, 2013;Holmes et al, 2017). A sustained-A model can produce remarkably regular firing patterns when stimulated by a steady depolarization, such as that provided by a step of current (Fig.…”