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

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

Zhang C; Beebe NL; Schofield BR; Pecka M; Burger RM

The Journal Of Neuroscience

2020

2020-11-30

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-nicotinic acetylcholine receptors (nAChRs) in rat SOC, suggesting possible engagement of acetylcholine (ACh)-mediated modulation of neural activity in the MNTB. However, the existence and nature of this putative modulation has 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 multi-barrel 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 anatomical evidence revealing novel cholinergic projections to MNTB arising from pontine and superior olivary nuclei.SIGNIFICANCE STATEMENTThis study is the first to physiologically probe how acetylcholine, a pervasive neuromodulator in the brain, influences the encoding of acoustic information by the MNTB, 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 anatomical 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.

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journalArticle

1529-2401 0270-6474

NEOMED College of Medicine

Department of Anatomy & Neurobiology

December 2020 List