Unraveling the molecular interactions between α7 nicotinic receptor and a RIC3 variant associated with backward speech.

Recent work putatively linked a rare genetic variant of the chaperone Resistant to Inhibitors of acetylcholinesterase (RIC3) (NM_024557.4:c.262G > A, NP_078833.3:p.G88R) to a unique ability to speak backwards, a language skill that is associated with exceptional working memory capacity. RIC3 is important for the folding, maturation, and functional expression of α7 nicotinic acetylcholine receptors (nAChR). We compared and contrasted the effects of RIC3G88R on assembly, cell surface expression, and function of human α7 receptors using fluorescent protein tagged α7 nAChR and Förster resonance energy transfer (FRET) microscopy imaging in combination with functional assays and 125I-α-bungarotoxin binding. As expected, the wild-type RIC3 protein was found to increase both cell surface and functional expression of α7 receptors. In contrast, the variant form of RIC3 decreased both. FRET analysis showed that RICG88R increased the interactions between RIC3 and α7 protein in the endoplasmic reticulum. These results provide interesting and novel data to show that a RIC3 variant alters the interaction of RIC3 and α7, which translates to decreased cell surface and functional expression of α7 nAChR.

Non-linguistic auditory speech processing.

OBJECTIVES: A method for testing auditory processing of non-linguistic speech-like stimuli was developed and evaluated. DESIGN: Monosyllabic words were temporally reversed and distorted. Stimuli were matched for spectrum and level. Listeners discriminated between distorted and undistorted stimuli. STUDY SAMPLE: Three groups were tested. The Normal group was comprised of 12 normal-hearing participants. The Senior group was comprised of 12 seniors. The Hearing Loss group was comprised of 12 participants with thresholds of at least 35 dB HL at one or more frequencies. RESULTS: The Senior group scored lower than the Normal group, and the Hearing Loss group scored lower than the Senior group. Scores for forward compressed speech were slightly higher than backward compressed speech but the difference was not statistically significant. Retest scores were slightly higher than scores on the first test, but the difference was not statistically significant. CONCLUSIONS: Large differences in discrimination of distorted speech were observed among the three groups. Age and hearing loss separately affected performance. The depressed performance of the Senior group may be a result of "hidden hearing loss" that is attributed to cochlear synaptopathy. The backward-distorted speech task may be a useful non-linguistic test of speech processing that is language independent.