Multiple Sources of Cholinergic Input to the Superior Olivary Complex.


Multiple Sources of Cholinergic Input to the Superior Olivary Complex.


Beebe NL; Zhang C; Burger RM; Schofield BR


Frontiers in Neural Circuits




The superior olivary complex (SOC) is a major computation center in the brainstem auditory system. Despite previous reports of high expression levels of cholinergic receptors in the SOC, few studies have addressed the functional role of acetylcholine in the region. The source of the cholinergic innervation is unknown for all but one of the nuclei of the SOC, limiting our understanding of cholinergic modulation. The medial nucleus of the trapezoid body, a key inhibitory link in monaural and binaural circuits, receives cholinergic input from other SOC nuclei and also from the pontomesencephalic tegmentum. Here, we investigate whether these same regions are sources of cholinergic input to other SOC nuclei. We also investigate whether individual cholinergic cells can send collateral projections bilaterally (i.e., into both SOCs), as has been shown at other levels of the subcortical auditory system. We injected retrograde tract tracers into the SOC in gerbils, then identified retrogradely-labeled cells that were also immunolabeled for choline acetyltransferase, a marker for cholinergic cells. We found that both the SOC and the pontomesencephalic tegmentum (PMT) send cholinergic projections into the SOC, and these projections appear to innervate all major SOC nuclei. We also observed a small cholinergic projection into the SOC from the lateral paragigantocellular nucleus of the reticular formation. These various sources likely serve different functions; e.g., the PMT has been associated with things such as arousal and sensory gating whereas the SOC may provide feedback more closely tuned to specific auditory stimuli. Further, individual cholinergic neurons in each of these regions can send branching projections into both SOCs. Such projections present an opportunity for cholinergic modulation to be coordinated across the auditory brainstem.


The superior olivary complex (SOC) serves as a major computation center in the brainstem auditory system. It participates in a variety of brainstem auditory circuits and is a hub for many ascending and descending auditory pathways. Among the many functions SOC serves in hearing, its roles in sound localization are well known (Harrison and Feldman, 1970; Grothe et al., 2010). Ascending auditory inputs to SOC emerge from the cochlear nucleus (CN; Cant and Casseday, 1986; Kuwabara et al., 1991; Thompson and Schofield, 2000). In turn, ascending projections from the SOC project primarily to nuclei of the lateral lemniscus and the inferior colliculus (IC), with smaller projections to the superior colliculus and auditory thalamus (Schofield et al., 2014; Mellott et al., 2018; Mansour et al., 2021). The SOC neurons that are responsible for computing the location of sound sources in the azimuth plane include medial superior olive (MSO) and lateral superior olive (LSO) neurons (Helfert and Aschoff, 1996). To ensure computational stability and accuracy, these neurons establish a complex and precise neural circuitry (Adams and Mugnaini, 1990; Schofield and Cant, 1991; Smith et al., 1998). In this network, the role of excitation and inhibition in shaping sound-evoked responses are well studied using simple acoustic stimuli (Brugge and Geisler, 1978; Albrecht et al., 2014; Grothe and Pecka, 2014). However, in response to more complex stimuli, the ability to maintain computational stability and accuracy may be challenged. Elevated input intensity or complicated input components causes synaptic depression, and weakened synapses affect the timing and strength of signal transmission among these SOC neurons (Banks and Smith, 1992; Grothe and Sanes, 1993; Song et al., 2005; Kopp-Scheinpflug et al., 2008). In addition to the known excitatory and inhibitory inputs, neuromodulatory mechanisms may be available to modify the SOC network dynamically for optimized performance. Numerous studies have suggested that SOC neurons employ local neuromodulation to regulate synaptic transmission to accommodate the complexity of acoustic inputs. In the MNTB, a number of ion channels and/or receptors are involved in regulating the signal transmission at its large and highly reliable synapse from the calyx of Held (Kopp-Scheinpflug et al., 2011). In the MSO, GABAB receptors modulate binaural synaptic inputs to ensure the precision of neural computation (Pecka et al., 2008; Hassfurth et al., 2010; Fischl et al., 2012). In the LSO, serotonergic modulation induces synaptic suppression of both excitatory and inhibitory inputs (Fitzgerald and Sanes, 1999).


Journal Article

NEOMED College

NEOMED College of Medicine

NEOMED Department

Department of Anatomy & Neurobiology

Update Year & Number

Jan to Aug list 2021


Beebe NL; Zhang C; Burger RM; Schofield BR, “Multiple Sources of Cholinergic Input to the Superior Olivary Complex.,” NEOMED Bibliography Database, accessed March 28, 2023,

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