Axonal Branching Patterns as Sources of Delay in the Mammalian Auditory Brainstem: A Re-Examination

Abstract

In models of temporal processing, time delays incurred by axonal propagation of action potentials play a prominent role. A preeminent model of temporal processing in audition is the binaural model of Jeffress (1948), which has dominated theories regarding our acute sensitivity to interaural time differences (ITDs). In Jeffress’ model a binaural cell is maximally active when the ITD is compensated by an internal delay, which brings the inputs from left and right ears in coincidence, and which would arise from axonal branching patterns of monaural input fibers. By arranging these patterns in systematic and opposite ways for the ipsi- and contralateral inputs, a range of length differences, and thereby of internal delays, is created so that ITD is transformed into a spatial activation pattern along the binaural nucleus. We reanalyze single, labeled and physiologically characterized, axons of spherical bushy cells of the cat anteroventral cochlear nucleus (AVCN) which project to binaural coincidence detectors in the medial superior olive (MSO). The reconstructions largely confirm the observations of two previous reports, but several features are observed which are inconsistent with Jeffress’ model. We found that ipsilateral projections can also form a caudally-directed delay line pattern, which would counteract delays incurred by caudally-directed contralateral projections. Comparisons of estimated axonal delays with binaural physiological data indicate that the suggestive anatomical patterns cannot account for the frequency-dependent distribution of best delays in the cat. Surprisingly, the tonotopic distribution of the afferents endings indicate that low CFs are under- rather than overrepresented in the MSO.

A functional circuit model of interaural time difference processing

“…Recent work by Seidl et al (2014) suggests that velocity is regulated differentially in ipsi-and contralateral portions of the efferent axons, and speculates on neuron-glia interactions as a possible mechanism for synchronization, although the precise method of modulation remains unclear (Cheng and Carr 2007). Mechanisms of input synchronization are similarly obscure in the mammalian equivalent of the NL, the medial superior olive (Karino et al 2011). In mammalian brain slices, the internal latency difference for the two excitatory pathways to the medial superior olive remains poorly understood (Jercog et al 2010), while anatomical reconstructions of the length differences, and thereby internal delays, cannot account for the distribution of best delays in the cat (Karino et al 2011).…”

“…Mechanisms of input synchronization are similarly obscure in the mammalian equivalent of the NL, the medial superior olive (Karino et al 2011). In mammalian brain slices, the internal latency difference for the two excitatory pathways to the medial superior olive remains poorly understood (Jercog et al 2010), while anatomical reconstructions of the length differences, and thereby internal delays, cannot account for the distribution of best delays in the cat (Karino et al 2011). …”

“…In vitro, Jercog et al (2010) found an internal latency difference between ispi-and contralateral inputs consistent with the position of the medial superior olive to one side of the brainstem and the shorter ipsilateral pathway. Careful reexamination of axonal branching patterns of physiologically characterized axons of spherical bushy cells of the cat anteroventral cochlear nucleus, which project to binaural coincidence detectors in the medial superior olive, led Karino et al (2011) to conclude that the anatomical patterns could not account for the frequency-dependent distribution of best delays in the cat (Hancock and Delgutte 2004;Joris et al 2005), and they suggest other mechanism(s) must contribute to the internal delays. Bremen and Joris (2013) further point out the importance of the relationship between delay and characteristic frequency, which constrains potential mechanism(s) that could generate best delays in the medial superior olive.…”

Modeling Binaural Responses in the Auditory Brainstem to Electric Stimulation of the Auditory Nerve

“…Our modeling results suggest that a gradient of biophysical properties might be required to achieve the good ITD sensitivity across a wide range of frequencies that is observed in physiological experiments from normal hearing animals (Kuwada et al 1987;Yin and Chan 1990). Since the MSO is tonotopically organized (Guinan et al 1972;Karino et al 2011) and MSO neurons have sharp frequency tuning (Yin and Chan 1990), this further suggests that biophysical properties of MSO neurons may be dependent on their location along the tonotopic axis. Baumann et al (2013) reported a gradient in the hyperpolarization-activated current I h along the tonotopic axis of gerbil MSO, with stronger I h in the high-frequency region.…”

Frequency-dependent interaural delays in the medial superior olive: implications for interaural cochlear delays

“…Jeffress (1948) originally proposed systematic delay lines of axonal conduction differences onto a binaural nucleus (now known to be the MSO); anatomical reconstruction of these axonal projections found the pattern of delays to be inconsistent with Jeffress' proposal and, further, could not fully account for the distribution of BDs observed physiologically (Karino et al 2011). Another mechanism of internal delay is the contralateral glycinergic inhibition onto MSO from the medial nucleus of the trapezoid body, whose pharmacological manipulation was found to shift the BDs of gerbil MSO neurons (Brand et al 2002;Pecka et al 2008).…”