| First Author | Bracic G | Year | 2022 |
| Journal | eNeuro | Volume | 9 |
| Issue | 2 | PubMed ID | 35410870 |
| Mgi Jnum | J:325609 | Mgi Id | MGI:7266067 |
| Doi | 10.1523/ENEURO.0118-22.2022 | Citation | Bracic G, et al. (2022) Impaired Subcortical Processing of Amplitude-Modulated Tones in Mice Deficient for Cacna2d3, a Risk Gene for Autism Spectrum Disorders in Humans. eNeuro 9(2):ENEURO.0118-22.2022 |
| abstractText | Temporal processing of complex sounds is a fundamental and complex task in hearing and a prerequisite for processing and understanding vocalization, speech, and prosody. Here, we studied response properties of neurons in the inferior colliculus (IC) in mice lacking Cacna2d3, a risk gene for autism spectrum disorders (ASDs). The alpha2delta3 auxiliary Ca(2+) channel subunit encoded by Cacna2d3 is essential for proper function of glutamatergic synapses in the auditory brainstem. Recent evidence has shown that much of auditory feature extraction is performed in the auditory brainstem and IC, including processing of amplitude modulation (AM). We determined both spectral and temporal properties of single- and multi-unit responses in the IC of anesthetized mice. IC units of alpha2delta3(-/-) mice showed normal tuning properties yet increased spontaneous rates compared with alpha2delta3(+/+) When stimulated with AM tones, alpha2delta3(-/-) units exhibited less precise temporal coding and reduced evoked rates to higher modulation frequencies (fm). Whereas first spike latencies (FSLs) were increased for only few modulation frequencies, population peak latencies were increased for fm ranging from 20 to 100 Hz in alpha2delta3(-/-) IC units. The loss of precision of temporal coding with increasing fm from 70 to 160 Hz was characterized using a normalized offset-corrected (Pearson-like) correlation coefficient, which appeared more appropriate than the metrics of vector strength. The processing deficits of AM sounds analyzed at the level of the IC indicate that alpha2delta3(-/-) mice exhibit a subcortical auditory processing disorder (APD). Similar deficits may be present in other mouse models for ASDs. |
