Medial Nucleus Of Trapezoid Body Neurons Research Articles

Endogenous Cholinergic Signaling Modulates Sound-Evoked Responses of the Medial Nucleus of the Trapezoid Body.

The medial nucleus of trapezoid body (MNTB) is a major source of inhibition in auditory brainstem circuitry. The MNTB projects well-timed inhibitory output to principal sound-localization nuclei in the superior olive (SOC) as well as other computationally important centers. Acoustic information is conveyed to MNTB neurons through a single calyx of Held excitatory synapse arising from the cochlear nucleus. The encoding efficacy of this large synapse depends on its activity rate, which is primarily determined by sound intensity and stimulus frequency. However, MNTB activity rate is additionally influenced by inhibition and possibly neuromodulatory inputs, albeit their functional role is unclear. Happe and Morley (2004) discovered prominent expression of α7 nAChRs in rat SOC, suggesting possible engagement of ACh-mediated modulation of neural activity in the MNTB. However, the existence and nature of this putative modulation have never been physiologically demonstrated. We probed nicotinic cholinergic influences on acoustic responses of MNTB neurons from adult gerbils (Meriones unguiculatus) of either sex. We recorded tone-evoked MNTB single-neuron activity in vivo using extracellular single-unit recording. Piggyback multibarrel electrodes enabled pharmacological manipulation of nAChRs by reversibly applying antagonists to two receptor types, α7 and α4β2. We observed that tone-evoked responses are dependent on ACh modulation by both nAChR subtypes. Spontaneous activity was not affected by antagonist application. Functionally, we demonstrate that ACh contributes to sustaining high discharge rates and enhances signal encoding efficacy. Additionally, we report anatomic evidence revealing novel cholinergic projections to MNTB arising from pontine and superior olivary nuclei.SIGNIFICANCE STATEMENT This study is the first to physiologically probe how acetylcholine, a pervasive neuromodulator in the brain, influences the encoding of acoustic information by the medial nucleus of trapezoid body, the most prominent source of inhibition in brainstem sound-localization circuitry. We demonstrate that this cholinergic input enhances neural discrimination of tones from noise stimuli, which may contribute to processing important acoustic signals, such as speech. Additionally, we describe novel anatomic projections providing cholinergic input to the MNTB. Together, these findings shed new light on the contribution of neuromodulation to fundamental computational processes in auditory brainstem circuitry and to a more holistic understanding of modulatory influences in sensory processing.

Ephrin-A2 and ephrin-A5 guide contralateral targeting but not topographic mapping of ventral cochlear nucleus axons.

BackgroundIn the auditory brainstem, ventral cochlear nucleus (VCN) axons project to the contralateral, but not ipsilateral, medial nucleus of trapezoid body (MNTB), terminating in the calyx of Held. Dorsal VCN neurons, representing high frequencies, synapse with medial MNTB neurons, while low frequency-coding ventral VCN neurons synapse with lateral MNTB neurons, reflecting tonotopic organization. The mechanisms that ensure strictly contralateral targeting and topographic ordering are incompletely understood. Here we examined the roles of ephrin-A signaling in both types of targeting.ResultsEphrin-A2 and ephrin-A5 are expressed in VCN cells during late embryonic and early postnatal development. At these ages ephrin-A2 is expressed in axons surrounding MNTB and ephrin-A5 is expressed in MNTB principal neurons. Ephrin-A2/A5 double knockout mice displayed axon targeting errors in which VCN axons project to MNTB on both sides of the brainstem, where they terminate in calyceal endings. Ephrin-A2 and ephrin-A5 single knockout mice showed a similar phenotype. In contrast to effects on contralateral targeting, ephrin-A2/A5 double knockout mice showed no defects in formation of tonotopically ordered projections from VCN to MNTB.ConclusionsThese findings demonstrate that distinct mechanisms regulate targeting of VCN axons to the contralateral MNTB and targeting to appropriate tonotopic locations. Ephrin-A signaling plays a similar role to ephrin-B signaling in the VCN-MNTB pathway, where both classes normally prevent formation of calyceal projections to ipsilateral MNTB. These classes may rely in part on common signaling pathways.

Developmental profiles of the intrinsic properties and synaptic function of auditory neurons in preterm and term baboon neonates.

The human fetus starts to hear and undergoes major developmental changes in the auditory system during the third trimester of pregnancy. Although there are significant data regarding development of the auditory system in rodents, changes in intrinsic properties and synaptic function of auditory neurons in developing primate brain at hearing onset are poorly understood. We performed whole-cell patch-clamp recordings of principal neurons in the medial nucleus of trapezoid body (MNTB) in preterm and term baboon brainstem slices to study the structural and functional maturation of auditory synapses. Each MNTB principal neuron received an excitatory input from a single calyx of Held terminal, and this one-to-one pattern of innervation was already formed in preterm baboons delivered at 67% of normal gestation. There was no difference in frequency or amplitude of spontaneous excitatory postsynaptic synaptic currents between preterm and term MNTB neurons. In contrast, the frequency of spontaneous GABA(A)/glycine receptor-mediated inhibitory postsynaptic synaptic currents, which were prevalent in preterm MNTB neurons, was significantly reduced in term MNTB neurons. Preterm MNTB neurons had a higher input resistance than term neurons and fired in bursts, whereas term MNTB neurons fired a single action potential in response to suprathreshold current injection. The maturation of intrinsic properties and dominance of excitatory inputs in the primate MNTB allow it to take on its mature role as a fast and reliable relay synapse.

Modelling homeostatic control of intrinsic excitability in single neurons

Event Abstract Back to Event Modelling homeostatic control of intrinsic excitability in single neurons Yann Sweeney1, 2* and Matthias Hennig1 1 University of Edinburgh, School of Informatics, United Kingdom 2 KTH Royal Institute of Technology, Department of Computational Biology, Sweden Intrinsic excitability in neurons is controlled by a number of homeostatic mechanisms, among which are the modulation of conductances in voltage-dependent ion channels and the modulation of the distance of the axon initial segment (AIS) from the soma. Due to their large size and good accessibility in slice experiments, a useful model system for these forms of homeostatic regulation are principal neurons of the medial nucleus of trapezoid body (MNTB) in the auditory brainstem. These act as relay neurons, receiving excitatory input and transmitting inhibitory signals to the auditory nuclei involved in sound localisation. One form of homeostasis of intrinsic excitability has been shown to be mediated by Nitric Oxide (NO), which is released by MNTB neurons in an activity-dependent manner and modulates Kv3 and Kv2 potassium channels conductance. We have investigated this homeostatic regulation in a multi-compartment MNTB neuron model, incorporating the localisation of ion channels in the soma and the AIS. The analysis of the model showed that the main effects of NO synthesis, a reduction of excitability and concomitant changes in action potential shape as observed in vitro (Steinert et al., Neuron, 2008, 2011), can be accounted for by increasing Kv2 conductances. Moreover, we found that the localisation of ion channels in the AIS, as opposed to the soma, results in a significantly faster action potential onset, with this effect increasing as the AIS is located more distally to the soma. Consistent with previous reports (Grubb & Burrone, Nature, 2010), the latter also increased neural excitability. We currently investigate how NO synthesis and AIS location affect the integration of synaptic inputs for different average activity levels and other statistical features of the input. Acknowledgements MRC Fellowship G0900425 EuroSPIN EMJD Fellowship EPSRC and BBSRC funded Doctoral Training Centre programme at School of Informatics, University of Edinburgh References [Steinert et al., 2008] Steinert, J. R., Kopp-Scheinpflug, C., Baker, C., Challiss, R. a J., Mistry, R., Haustein, M. D., Griffin, S. J., et al. (2008). Nitric oxide is a volume transmitter regulating postsynaptic excitability at a glutamatergic synapse. Neuron, 60(4), 642-56. Elsevier Inc. doi:10.1016/j.neuron.2008.08.025 [Steinert et al., 2011] Steinert, J. R., Robinson, S. W., Tong, H., Haustein, M. D., Kopp-Scheinpflug, C., & Forsythe, I. D. (2011). Nitric oxide is an activity-dependent regulator of target neuron intrinsic excitability. Neuron, 71(2), 291-305. Elsevier Inc. doi:10.1016/j.neuron.2011.05.037 [Grubb & Burrone, 2010] Grubb, M. S., & Burrone, J. (2010). Activity-dependent relocation of the axon initial segment fine-tunes neuronal excitability. Nature, 465(7301), 1070-4. Nature Publishing Group. doi:10.1038/nature09160 Keywords: axon initial segment, Compartmental neuron model, Homeostasis, Ion Channels, MNTB, Nitric Oxide Conference: Bernstein Conference 2012, Munich, Germany, 12 Sep - 14 Sep, 2012. Presentation Type: Poster Topic: Other Citation: Sweeney Y and Hennig M (2012). Modelling homeostatic control of intrinsic excitability in single neurons. Front. Comput. Neurosci. Conference Abstract: Bernstein Conference 2012. doi: 10.3389/conf.fncom.2012.55.00239 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 18 Sep 2012; Published Online: 12 Sep 2012. * Correspondence: Mr. Yann Sweeney, University of Edinburgh, School of Informatics, Edinburgh, Edinburgh, EH8 9AB, United Kingdom, yann.sweeney@ed.ac.uk Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. 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