How we process sensory stimuli from the world around us is intricately modulated so that we sense what we want and discard the rest to avoid overtaxing our neural systems. A new study reports, modulation of neural activity by acetylcholine inputs helps parse tones from noise and may contribute to processing acoustic signals such as speech.

Acetylcholine, a ubiquitous neuromodulator in the brain, influences the encoding of acoustic information at a brainstem nucleus that inhibits neural circuits responsible for sound-localization.

The authors describe novel anatomical projections that provide cholinergic input to the brainstem auditory nucleus. These cholinergic inputs enhance neural discrimination of tones from noise stimuli, facilitating the processing of acoustic signals such as speech.

The findings have been described in an article, “Endogenous Cholinergic Signaling Modulates Sound-evoked Responses of the Medial Nucleus of the Trapezoid Body,” published in The Journal of Neuroscience.

Auditory nuclei in the brain stem
This image shows histological confirmation of recording sites. Fluoro-Gold deposited at the end of separate recordings from MNTB and MSO (dotted areas) are clearly separated and localized to target nuclei, confirming precise targeting to recording sites based on acoustically driven responses. [Chao Zhang, Nichole L. Beebe, Brett R. Schofield, Michael Pecka and R. Michael Burger]
“This study will likely bring new attention in the field to the ways in which circuits like this, widely considered a ‘simple’ one, are in fact highly complex and subject to modulatory influence like higher regions of the brain,” says R. Michael Burger, PhD, Department of Biological Sciences, Lehigh University, Pennsylvania, senior author on the study.

Inhibition of auditory sensory signals is important for estimating the precise timing and intensity of sound cues. The superior olivary complex (SOC) in the brainstem is a major hub of auditory neural circuits and is associated with processing location information from sound signals, in mammals. Within the SOC lies a nucleus that converts excitatory signals from the ear on the opposite side of the body, to inhibitory signals with incredible fidelity. This nucleus is called the medial nucleus of trapezoid body (MNTB) and is a principal source of inhibitory signals to other nuclei, including the medial superior olive (MSO).

MNTB neurons were previously thought to be part of a simple neural circuit driven by a single large excitatory synapse and influenced by local inhibitory inputs. This study describes novel anatomical projections that provide acetylcholine inputs from various sources on the MNTB neurons and demonstrates that in addition to previously known inputs on these neurons, acetylcholine inputs modulate their activity enhancing neural discrimination of tones from noise stimuli.

In noisy surroundings the function of MNTB is further challenged, the authors note. Auditory neurons must quickly adapt to rapid variations in sound level or signal-to-noise ratio. Neuromodulator circuits offer an adaptive mechanism that enhances the computational power of auditory circuits. The study shows that neuromodulator cholinergic signaling influences the ability of MNTB neurons to sustain robust detection of tone stimuli in the presence of a noisy background. The authors also show MNTB neurons’ ability to detect signals in noise is significantly degraded when cholinergic inputs are pharmacologically blocked.

The current study identifies anatomical sources of cholinergic projections to the MNTB. The authors deposited retrograde tracers on MNTB neurons and examined the regions of brain that contained tracer-filled neurons to identify sources of cholinergic input to the MNTB. These retrograde labeling studies revealed that the MNTB receives cholinergic projections from multiple sound-driven sources.

“This modulation appears to help these neurons detect faint signals in noise,” says Burger. “You can think of this modulation as akin to shifting an antenna’s position to eliminate static for your favorite radio station.”

The authors record MNTB neuron responses to acoustic stimuli in the adult gerbil in vivo while performing pharmacological manipulations of nicotinic acetylcholine receptors and show that this endogenous receptor activity differentially modulates responses to tone and noise stimuli.

The study shows that cholinergic inputs on the MNTB neurons contributes to the response magnitude for large (suprathreshold) stimuli but does not influence threshold values or spontaneous neural spiking in MNTB neurons.

“In this paper, we show that modulatory circuits have a profound effect on neurons in the sound localization circuitry, at very low foundational level of the auditory system,” adds Zhang.

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