Presenting Author:

Xiaodong Tan, Ph.D.

Principal Investigator:

Claus-Peter Richter

Department:

Otolaryngology - Head and Neck Surgery

Keywords:

Infrared neural stimulation, hair cells, spiral ganglion neurons, congenital deaf, auditory brainstem response, micro-co... [Read full text] Infrared neural stimulation, hair cells, spiral ganglion neurons, congenital deaf, auditory brainstem response, micro-computed tomography [Shorten text]

Location:

Third Floor, Feinberg Pavilion, Northwestern Memorial Hospital

B127 - Basic Science

Laser Induced Auditory Neural Responses in congenital deaf animals

Background Two of the basic components in the cochlea for normal hearing are sensory hair cells (HCs) and spiral ganglion neurons (SGNs). The loss of HCs is one of the leading causes of deafness, while the restoration through the direct activation of SGNs are possible by cochlear implants (CIs). The application of infrared neural stimulation (INS) in novel laser-based CIs has been proposed, with the potential benefits of higher spatial resolution and larger number of independent channels. While activation of SGNs by INS has been accomplished in different laboratories, irreconcilable controversies exist regarding whether the stimulation is dominated by laser-induced photoacoustic effects or by direct stimulation of SGNs. In this study, INS was applied to three strains of transgenic mice which are congenitally deaf but with different causalities. Atoh1 conditional knock-out (CKO) mice suffer from a major HC loss and underdeveloped cochleae. Knock-in with Neurog1 (Neurog1 KI) substituting Atoh1 rescued a large number of HCs, while no hearing restoration is achieved. VGlut3 knock-out (VGlut3 -/-) mice have no synaptic transmission between inner HCs and SGNs. Same study was also performed on 2 deaf white cats. Methods Infrared light was delivered with a 200 µm optical fiber to the cochlea of the mice aged at 3-5 months. Optical irradiation and acoustic evoked auditory brainstem responses (ABRs) were recorded. Same stimuli were also delivered to 2 deaf white cats at the age of over 5 years and the ABRs were recorded. Immuno-fluorescence histochemistry of whole mount cochleae and synchrotron X-ray micro-computed tomography (µCT) imaging of the intact cochleae were performed to verify and evaluate the survival of HCs and SGNs. Results 1. None of the three strains of mice has any residual hearing even at high sound levels, although SGNs are intact in the newborns of Neurog1 KI (P7) and Vglut3 -/- mice; 2. INS induced ABRs were measured in the apical to the middle but not in the basal turn of Neurog1 KI (5 out of 6, 5/6) and Vglut3-/- (2/3) mice; 3. X-ray µCT imaging revealed a complete loss of HCs and SGNs in the basal turn and a large amount of surviving HCs and SGNs in the apical to middle turn of Neurog1 KI mice cochleae; 4. Optical stimuli also evoked ABRs in deaf white cats. Conclusions 1. Optical, but not acoustic stimulation can induce ABRs and CAPs in congenital deaf animals. 2. INS evoked auditory neural response in congenital deaf animals are location specific and dependent on the survival of SGNs. This result suggests a direct activation of SGNs by INS. 3. Disorganization of the cochlea and abnormal distribution of HCs instead of the loss of nerve innervation might be the reason of the deafness of the Neurog1 KI mice. Funding This work is supported by the NIH, R01-DC011855 to CPR and R03 DC013655 to IJ.