The role of the Ventral Nucleus of the Trapezoid Body in the auditory prepulse inhibition of the acoustic startle reflex

• Published in: Hearing research 2024-09, Vol.450, p.109070, Article 109070
• Main Authors: Barioni, N.O., Beduschi, R.S., da Silva, A.V., Martins, M.G., Almeida-Francia, C.C.D., Rodrigues, S.A., López, D.E., Gómez-Nieto, R., Horta-Júnior, J.A.C.
• Format: Article
• Language: English
• Subjects: Acoustic Stimulation; Animals; Auditory Pathways - metabolism; Auditory Pathways - physiology; Auditory prepulse inhibition pathway; Choline O-Acetyltransferase - metabolism; Cholinergic Neurons - metabolism; Cholinergic Neurons - physiology; Cholinergic projections; Cochlear Nerve - metabolism; Cochlear Nerve - physiology; Cochlear root neurons; Evoked Potentials, Auditory, Brain Stem; Immunotoxins; Male; Prepulse Inhibition - physiology; Rats; Rats, Sprague-Dawley; Reflex, Startle; Ribosome Inactivating Proteins, Type 1; Saporin immunolesion; Saporins - metabolism; Sensorimotor gating; Trapezoid Body - metabolism; Trapezoid Body - physiology
• ISSN: 0378-5955; 1878-5891; 1878-5891
• DOI: 10.1016/j.heares.2024.109070

•Olivocochlear and non-olivocochlear neurons in the VNTB lack a distinct topographic pattern, exhibiting a mixed arrangement.•A notable proportion of VNTB cholinergic neurons projecting to the cochlear root nucleus is concentrated at rostral levels.•The VNTB plays a role in the prepulse inhibition of acoustic startle reflex, particularly at short interstimulus intervals.•Non-olivocochlear VNTB neurons are involved in the rapid top-down cholinergic pathway of auditory prepulse inhibition. Cholinergic signaling is essential to mediate the auditory prepulse inhibition (PPI), an operational measure of sensorimotor gating, that refers to the reduction of the acoustic startle reflex (ASR) when a low-intensity, non-startling acoustic stimulus (the prepulse) is presented just before the onset of the acoustic startle stimulus. The cochlear root neurons (CRNs) are the first cells of the ASR circuit to receive cholinergic inputs from non-olivocochlear neurons of the ventral nucleus of the trapezoid body (VNTB) and subsequently decrease their neuronal activity in response to auditory prepulses. Yet, the contribution of the VNTB-CRNs pathway to the mediation of PPI has not been fully elucidated. In this study, we used the immunotoxin anti-choline acetyltransferase (ChAT)-saporin as well as electrolytic lesions of the medial olivocochlear bundle to selectively eliminate cholinergic VNTB neurons, and then assessed the ASR and PPI paradigms. Retrograde track-tracing experiments were conducted to precisely determine the site of lesioning VNTB neurons projecting to the CRNs. Additionally, the effects of VNTB lesions and the integrity of the auditory pathway were evaluated via auditory brain responses tests, ChAT- and FOS-immunohistochemistry. Consequently, we established three experimental groups: 1) intact control rats (non-lesioned), 2) rats with bilateral lesions of the olivocochlear bundle (OCB-lesioned), and 3) rats with bilateral immunolesions affecting both the olivocochlear bundle and the VNTB (OCB/VNTB-lesioned). All experimental groups underwent ASR and PPI tests at several interstimulus intervals before the lesion and 7, 14, and 21 days after it. Our results show that the ASR amplitude remained unaffected both before and after the lesion across all experimental groups, suggesting that the VNTB does not contribute to the ASR. The%PPI increased across the time points of evaluation in the control and OCB-lesioned groups but not in the OCB/VNTB-lesioned group. At the