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The largest nucleus of the human superior oliva ry complex is the medial superior olive (MSO), whi ch generates sensitivity to interaural time differ ences (ITD), the main cue for horizontal sound loc alization, by comparing the inputs it receives fro m both ears. The MSO is dysmorphic in autistic spe ctrum disorders, corresponding to the frequent occ urrence of auditory dysfunction in these patients. The computation resulting in sensitivity to ITD is thought to be coincidence detection, a n operation that allows neurons to decode time cod es, but it has not been studied directly in vivo d ue to the absence of intracellular recor dings. MSO neurons are tuned to differen t best ITDs, which means that there should be an internal delay in the brainstem compensat ing for the external ITD. The source of internal delay has been a controversial issue . MSO responses to stimuli beyond tones are a lmost completely absent from the literature. Besid es excitatory inputs, MSO neurons receive inhibito ry inputs from each ear, from the latera l nucleus of the trapezoid body (LNTB; ipsilateral ly) and the medial nucleus of the trapezoid b ody (MNTB; contralaterally). Especially the proper ties of the LNTB input are unclear, due to th e lack of in vivo recordings from retrie ved cells.We performed in vivo whole ce ll recordings from MSO and LNTB neurons in th e Mongolian gerbil, and labeled these neurons ¨with biocytin. Intracellular recordings during mo naural and binaural sounds (tones and noise) allow ed us to separate subthreshold (input) from s uprathreshold (output) activity and study the ¨neural computation performed. Pharmacological man ipulation were used to isolate excitatory and ¨inhibitory inputs. Finally, we performed a c oincidence 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 ps eudobinaural functions.Intracellular recordi ngs from MSO neurons show that these neurons mostly receive excitatory postsynaptic potentials (EPSP s) and only few and small inhibitory pos tsynaptic potentials (IPSPs). Pharmacological mani pulation revealed that ITD tuning of the neurons is not systematically affected by inhibit ion, in contrast with an earlier hy pothesis. Instead, we find a shift between the summation of subthreshold inputs and suprat hreshold ITD tuning, due to subtle asymmetrie s in the temporal pattern of EPSPs that¨ differentially activate voltage-gated potassi um channels, providing an unexpected source of internal delay. Responses from tones at dif ferent frequencies and noise bandwidths show¨ an impressive boost of MSO output to low ¨frequency tones and narrowband noise, due to decr easing coherence of input spikes for higher f requencies and broader bandwidths. Coincidence cou nts of responses of trapezoid body fibers result i n pseudobinaural noise delay functions and rate-co rrelation functions. We show that multiple in puts are needed per side to get ade quate output spike rates; that monaural coinc idences have to be suppressed over binau ral ones to maintain binaural sensitivity and that the neuron needs to be sensitive to sin gle coinciding spikes. We find anatomical evidence ¨for at least two subdivisions in the LN TB, termed pv (posteroventral) LNTB and m (main) L NTB. These divisions also have different phys iological properties. We find an unexpected projec tion from the lateral superior olive (LSO) to the¨ LNTB.We conclude that the MSO performs adapt ive coincidence detection rather than instant aneous coincidence detection and is sensitive to a ¨low number of input spikes. In addition to i ts binaural properties, MSO neurons are well place d to detect low frequency sounds. The LNTB is ¨composed of several subdivisions that can be ¨distinguished anatomically and physiologically, a nd receives an unexpected input from the ¨LSO.Publication status: acceptedKU Leuven publication type: THNumber of times cited:0Appears in Collections:Laboratory for Auditive NeurophysiologyResearch Group NeurophysiologyFiles in This Item:There are no files associated with this item.