Safety margin evaluations for transtympanic laser stimulation of the cochlea from the outer ear in Mongolian gerbils (Meriones unguiculatus)

Abstract

Infrared laser stimulation of the cochlea has been proposed as a possible alternative to conventional auditory prostheses. The safety margin of laser stimulation must be determined for the practical application of the laser to a prosthesis. This study assessed the effect of laser-induced damage to the cochlea on auditory perception. To examine the effects of laser-induced injury of the auditory system on the perception of auditory stimuli, we trained Mongolian gerbils (Meriones unguiculatus) using a head-fixed classical conditioning task. White noise of 80 dB sound pressure level (SPL) was presented as a conditioned stimulus for a reward (a drop of water), and licking behavior was recorded as a conditioned response. After training, an optic fiber was inserted into the ear canal. Each subject was exposed to continuous pulsed laser exposure of 1.6, 3.3, 6.6, 26.4, 52.8, or 105.6 W/cm2 for 15 h. White noise of various intensities was presented without pairing it with water before and after laser exposure, to assess the decrease in auditory perception due to laser-induced injury. The licking rate did not change after laser exposure of 6.6 W/cm2 or weaker but drastically decreased after 26.4 W/cm2 or higher. These results suggest that the injury threshold in Mongolian gerbils for laser stimulation is between 6.6 and 26.4 W/cm2; laser exposure over 6.6 W/cm2 could be out of the safety margin. These findings will contribute to the appropriate delimitation of safe and effective laser stimulation parameters in future research.

Non-invasive optical synthetization of hearing sensation in non-genetically modified animal

“…Our previous study demonstrated that a transtympanic laser at 6.6 W/cm 2 did not induce observable thermal elevation and did not cause histological, electrophysiological, or behavioral damage in Mongolian gerbils ( 11 ). Our current data show that a laser-evoked behavioral response started to be observed at approximately 1.1 mJ/cm 2 or more, with a pulsed laser train at 4000 Hz delivered for 500 ms (i.e., radiant energy of the stimulus was 2.2 W/cm 2 ), indicating that laser-evoked perception could be generated within a safety margin of the laser stimulation (Fig.…”

“…After surgery, all subjects were individually housed and given a recovery period of at least two days before training commenced. The animal surgery followed the same procedure as in our previous studies ( 4, 5 ).…”

“…The laser was delivered through an optical fiber (diameter: 100 μm; NA: 0.22) inserted mediolaterally into the left outer ear canal, with the tip angled rostrally by 10° and dorsally by 5° using a micromanipulator (MM-3; Narishige, Tokyo, Japan) in awake head-fixed subjects. The optic fiber tip was fixed at approximately 0.7 mm (the distance between the cochlea and fiber tip was about 2.2 mm) in front of the tympanic membrane to ensure transtympanic irradiation of the cochlea from the outer ear, as described in our previous reports ( 3–5, 8 ). The laser beam profile at the cochlea (2.2 mm from the fiber tip) was measured, as in previous studies ( 4, 5 ).…”

“…Behavioral experiments and electrophysiological recording were performed in the same 60 × 60 × 60-cm (W × L × H) soundproof box, following our previous study ( 5 ). Each subject was positioned on a custom-designed covered platform with a copper sheet.…”

“…Previous studies have explored the relationship between the irradiation site of the cochlea and laser-evoked neural responses, highlighting lasers’ ability to elicit spatially specific neural activities ( 8, 9 ). Our prior research utilized the contactless and penetrative nature of laser stimulation through thin tissues, demonstrating that transtympanic laser irradiation of the cochlea from the outer ear could elicit cochlear responses ( 10, 11 ) and auditory cortical activities ( 12 ), bypassing the middle ear. These findings suggest that auditory prostheses incorporating laser stimulation could offer a less invasive means of providing hearing sensation compared to traditional electric cochlear implants, although debates persist about the precision of spectral information ( 10, 11 ).…”