![]() Thus, potential hearing loss present at the ages studied in C57BL/6 mice could have contributed to the observation of local frequency preference heterogeneity. In contrast, mice of the CBA strain or F1 offspring of C57BL/6 mice and CBA mice retain normal hearing into adulthood 31, 32, 33, 34, 35, 36. However, the C57BL/6 strain carries a mutant cdh23 allele 23, 24, 25, 26, 27, 28, 29 which leads to a progressive loss of hair cells from the basal turn of the cochlea 30, making these mice an ideal model of presbycusis 31, 32, 33, 34, 35. Many functional studies in mouse have been performed on mice on the C57BL/6 background. The precise degree of heterogeneity varies slightly between these studies, and this difference might be due to differences in anesthetic condition, cell inclusion criteria, tonal stimuli used, and/or species. However, the application of large-scale high-resolution optical techniques in mice or rats using synthetic dyes (OGB1, Fluo4, or Cal-520) or sensitive genetically encoded Ca 2+ indicators (GCaMP6) has shown that on the cellular level the organization of tuning in A1 is more heterogeneous than previously appreciated 1, 2, 3, 4, 5, 6, 19, 20, 21, 22 suggesting that at least in rodent layer 2/3 (L2/3) functional tonotopic maps might be fractured. A classic hallmark of A1 organization in all species has been the discovery of tonotopic maps which describe a smooth distribution of tone preference across the surface of the primary and secondary auditory fields when probed with low spatial resolution techniques 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18. Recent studies have investigated the functional organization and circuitry of mouse auditory cortex 1, 2, 3, 4, 5, 6. The primary auditory cortex (A1) plays a key role for sound perception since it represents one of the first cortical processing stations for sounds. The cerebral cortex is uniquely adapted to encode behaviorally relevant stimuli and generate appropriate behavioral actions. Our results demonstrate that the tone evoked responses and frequency representation in A1 of adult C57BL/6 and F1 (CBAxC57) mice are largely similar. The spatial heterogeneity of frequency preference was present in both strains with F1 (CBAxC57) mice exhibiting higher tuning diversity across all measured length scales. Frequency selectivity was slightly higher in C57BL/6 mice while neurons in F1 (CBAxC57) mice showed a greater sound-level sensitivity. Pure tones recruited neurons of widely ranging frequency preference in both layers and strains with neurons in F1 (CBAxC57) mice exhibiting a wider range of frequency preference particularly to higher frequencies. We used in vivo 2-photon imaging of pyramidal neurons in cortical layers L4 and L2/3 of awake mouse primary auditory cortex (A1) to characterize the populations of neurons that were active to tonal stimuli. Since potential strain differences could exist in A1 organization between strains, we performed comparative analysis of neuronal populations in A1 of adult (~ 10 weeks) C57BL/6 mice and F1 (CBAxC57) mice. In contrast, mice on the CBA background retain better hearing sensitivity in old age. However, many of these studies were performed in mice on the C57BL/6 background which develop high frequency hearing loss with age making them a less optimal choice for auditory research. Recent studies have shown that on the cellular level the frequency organization of A1 is more heterogeneous than previously appreciated.
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