GC-B Deficient Mice With Axon Bifurcation Loss Exhibit Compromised Auditory Processing

Area of Science:

• Neuroscience
• Auditory system physiology
• Molecular signaling in development

Background:

• Sensory axon branching is vital for neural circuit formation and information processing.
• C-type natriuretic peptide (CNP) and its receptor guanylyl cyclase B (GC-B) pathway regulate axon bifurcation.
• Impaired GC-B function in mice affects auditory nerve (AN) fiber bifurcation but not basal hearing.

Purpose of the Study:

• To investigate the role of GC-B in auditory processing and temporal precision.
• To elucidate the functional consequences of GC-B-mediated axon bifurcation in the auditory system.
• To examine the impact of GC-B inactivation on auditory nerve responses and brainstem processing.

Main Methods:

• Targeted inactivation of the GC-B gene (Npr2) in mice (GC-B KO).
• Audiometric threshold measurements and analysis of cochlear hair cell markers.
• Evaluation of efferent cholinergic feedback, sound-evoked AN responses, and brainstem auditory evoked potentials.
• Assessment of acoustic startle response (ASR) and prepulse inhibition of ASR.

Main Results:

• GC-B KO mice exhibited elevated audiometric thresholds.
• Reduced efferent cholinergic feedback to cochlear hair cells was observed in GC-B KO mice.
• Elevated sound-evoked AN responses, delayed brainstem responses, and altered auditory steady-state responses were found in GC-B KO mice.
• Impaired temporal precision in auditory processing, including ASR and prepulse inhibition, was evident.

Conclusions:

• GC-B-controlled axon bifurcation of spiral ganglion neurons is essential for proper second-order neuron activation in the hindbrain.
• GC-B signaling is a prerequisite for accurate temporal auditory processing, likely via efferent feedback circuits.
• Cranial nerve bifurcation patterns shape sensory information processing and feedback control.