Title: Intracellular Study of a Timing Circuit in the Auditory Brainstem
Other Titles: Intracellulaire Studie van een Tijdscircuit in de Auditieve Hersenstam
Authors: Franken, Tom
Issue Date: 17-Mar-2015
Abstract: The largest nucleus of the human superior olivary complex is the medial superior olive (MSO), which generates sensitivity to interaural time differences (ITD), the main cue for horizontal sound localization, by comparing the inputs it receives from both ears. The MSO is dysmorphic in autistic spectrum disorders, corresponding to the frequent occurrence of auditory dysfunction in these patients. The computation resulting in sensitivity to ITD is thought to be coincidence detection, an operation that allows neurons to decode time codes, but it has not been studied directly in vivo due to the absence of intracellular recordings. MSO neurons are tuned to different best ITDs, which means that there should be an internal delay in the brainstem compensating for the external ITD. The source of internal delay has been a controversial issue. MSO responses to stimuli beyond tones are almost completely absent from the literature. Besides excitatory inputs, MSO neurons receive inhibitory inputs from each ear, from the lateral nucleus of the trapezoid body (LNTB; ipsilaterally) and the medial nucleus of the trapezoid body (MNTB; contralaterally). Especially the properties of the LNTB input are unclear, due to the lack of in vivo recordings from retrieved cells.
We performed in vivo whole cell recordings from MSO and LNTB neurons in the Mongolian gerbil, and labeled these neurons with biocytin. Intracellular recordings during monaural and binaural sounds (tones and noise) allowed us to separate subthreshold (input) from suprathreshold (output) activity and study the neural computation performed. Pharmacological manipulation were used to isolate excitatory and inhibitory inputs. Finally, we performed a coincidence analysis of broadband responses of cat trapezoid body fibers to study the effect of number of inputs, binaural and monaural coincidence threshold and coincidence window on pseudobinaural functions.
Intracellular recordings from MSO neurons show that these neurons mostly receive excitatory postsynaptic potentials (EPSPs) and only few and small inhibitory postsynaptic potentials (IPSPs). Pharmacological manipulation revealed that ITD tuning of the neurons is not systematically affected by inhibition, in contrast with an earlier hypothesis. Instead, we find a shift between the summation of subthreshold inputs and suprathreshold ITD tuning, due to subtle asymmetries in the temporal pattern of EPSPs that differentially activate voltage-gated potassium channels, providing an unexpected source of internal delay. Responses from tones at different frequencies and noise bandwidths show an impressive boost of MSO output to low frequency tones and narrowband noise, due to decreasing coherence of input spikes for higher frequencies and broader bandwidths. Coincidence counts of responses of trapezoid body fibers result in pseudobinaural noise delay functions and rate-correlation functions. We show that multiple inputs are needed per side to get adequate output spike rates; that monaural coincidences have to be suppressed over binaural ones to maintain binaural sensitivity and that the neuron needs to be sensitive to single coinciding spikes. We find anatomical evidence for at least two subdivisions in the LNTB, termed pv (posteroventral) LNTB and m (main) LNTB. These divisions also have different physiological properties. We find an unexpected projection from the lateral superior olive (LSO) to the LNTB.
We conclude that the MSO performs adaptive coincidence detection rather than instantaneous coincidence detection and is sensitive to a low number of input spikes. In addition to its binaural properties, MSO neurons are well placed to detect low frequency sounds. The LNTB is composed of several subdivisions that can be distinguished anatomically and physiologically, and receives an unexpected input from the LSO.
Publication status: published
KU Leuven publication type: TH
Appears in Collections:Research Group Neurophysiology
Laboratory for Auditive Neurophysiology

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