Altered population activity and local tuning heterogeneity in auditory cortex of Cacna2d3-deficient mice

The alpha(2)delta 3 auxiliary subunit of voltage-activated calcium channels is required for normal synaptic transmission and precise temporal processing of sounds in the auditory brainstem. In mice its loss additionally leads to an inability to distinguish amplitude-modulated tones. Furthermore, loss of function of alpha(2)delta 3 has been associated with autism spectrum disorder in humans. To investigate possible alterations of network activity in the higher-order auditory system in alpha(2)delta 3 knockout mice, we analyzed neuronal activity patterns and topography of frequency tuning within networks of the auditory cortex (AC) using two-photon Ca2+ imaging. Compared to wild-type mice we found distinct subfield-specific alterations in the primary auditory cortex, expressed in overall lower correlations between the network activity patterns in response to different sounds as well as lower reliability of these patterns upon repetitions of the same sound. Higher AC subfields did not display these alterations but showed a higher amount of well-tuned neurons along with lower local heterogeneity of the neurons' frequency tuning. Our results provide new insight into AC network activity alterations in an autism spectrum disorder-associated mouse model.

Automated summary

Loss of the alpha(2)delta 3 auxiliary subunit leads to an inability to distinguish amplitude-modulated tones and has been associated with autism spectrum disorder. Analysis of neuronal activity in the auditory cortex reveals subfield-specific alterations, with higher subfields showing more well-tuned neurons and lower local heterogeneity.