Abstract
The primary auditory cortex (A1) plays a key role for sound perception since it represents one of the first cortical processing stations for sounds. Recent studies have shown that on the cellular level the frequency organization of A1 is more heterogeneous than previously appreciated. 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. In contrast, mice on the CBA background retain better hearing sensitivity in old age. 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. 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. 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. Frequency selectivity was slightly higher in C57BL/6 mice while neurons in F1 (CBAxC57) mice showed a greater sound-level sensitivity. The spatial heterogeneity of frequency preference was present in both strains with F1 (CBAxC57) mice exhibiting higher tuning diversity across all measured length scales. Our results demonstrate that the tone evoked responses and frequency representation in A1 of adult C57BL/6 and F1 (CBAxC57) mice are largely similar.
Highlights
The cerebral cortex is uniquely adapted to encode behaviorally relevant stimuli and generate appropriate behavioral actions
When C57BL/6 mice are split up by GCaMP6s line, we find that Emx1-Cre based mice have lower Receptive Field Sum (RFS) values than F1 (CBAxC57) (p < 2.7 × 10–9, Wilcoxon rank sum), yet Thy1-GC6 mice have similar values to F1 (CBAxC57) (p > 0.73, Wilcoxon rank sum)
We find that median characteristic frequency (CF) was generally the same in both layers of C57BL/6 mice (8.5 kHz) and across both layers of F1 (CBAxC57) mice (12 kHz) (Fig. 3D). IQRCF was higher in F1 (CBAxC57) mice than in C57BL/6 mice in both layer 2/3 (L2/3) and L4 (Fig. 3E). STDCF was significantly higher in F1 (CBAxC57) mice than in C57BL/6 mice in both L2/3 and L4 (Fig. 3F) (pL2/3 < 0.004, pL4 < 10–3, two-sample t-test)
Summary
The cerebral cortex is uniquely adapted to encode behaviorally relevant stimuli and generate appropriate behavioral actions. Potential hearing loss present at the ages studied in C57BL/6 mice could have contributed to the observation of local frequency preference heterogeneity. We aimed to test if the laminar differences in functional responses and organization present under anesthetized conditions in C57BL/6 mice were present in awake animals and if such organizational features were present in F1 (CBAxC57) mice. Our observations show that while there are differences in the tuning of single neurons between mice, there remains laminar differences in both frequency selectivity and local heterogeneity of frequency preference present in both strains. Our results here along with previously published results show that the local heterogeneity of frequency preference is present in both anesthetized and awake mice and across mouse strains. The heterogeneity of pure tone frequency selectivity forms an organizational principle of auditory cortex organization in mice
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