Local versus global scales of organization in auditory cortex

Abstract

Topographic organization is a hallmark of sensory cortical organization. Topography is robust at spatial scales ranging from hundreds of microns to centimeters, but can dissolve at the level of neighboring neurons or subcellular compartments within a neuron. This dichotomous spatial organization is especially pronounced in the mouse auditory cortex, where an orderly tonotopic map can arise from heterogeneous frequency tuning between local neurons. Here, we address a debate surrounding the robustness of tonotopic organization in the auditory cortex that has persisted in some form for over 40 years. Drawing from various cortical areas, cortical layers, recording methodologies, and species, we describe how auditory cortical circuitry can simultaneously support a globally systematic, yet locally heterogeneous representation of this fundamental sound property.

Keywords: auditory cortex; calcium; electrophysiology; frequency; heterogeneity; homogeneity; imaging; layers; maps; resolution; scale.

Figure 1. Evidence for order: Large-scale tonotopy within the middle cortical layers of the mouse auditory cortex

A) Auditory thalamocortical slice immunoreacted for parvalbumin (blue). Retrograde tracers (Cholera toxin β subunit) conjugated to a green or red fluorophore were injected into a low- (7 kHz) or mid-frequency (22.6 kHz) region of the A1 map, respectively. The A1 injection sites appear at the left of the image, the labeled thalamocortical axons in the middle of the image, and the retrogradely labeled MGBv cell bodies to the right of the image. Scale bar = 0.25 mm. B) A tessellated best frequency (frequency that elicits the most spikes across all levels) map delineated from 300 multiunit recording sites in the middle layers of the area identified in (A). Note the clear tonotopic gradient within A1 and AAF compared to the non-tonotopic organization of the remaining fields. Right, Tonal receptive fields from A1 (top and middle) and A2 (bottom) measured at the numbered locations shown on the tessellated map. C) Best frequency distribution along the caudal-to-rostral axis through A1 and AAF. Distance is relative to the mirror reversal in best frequency that indicates the boundary between each field. Data from individual mice are represented by different colors. Solid black lines indicate the linear fit of the A1 and AAF data. See [25] for further details regarding data in A–C

Figure 2. Evidence for disorder: Single cell imaging shows heterogeneity in supragranular layers

A) Reconstruction of two imaging sites from layer 2/3 in one mouse. Characteristic frequency (CF, frequency tuning at threshold) for each cell illustrates both the local heterogeneity at local scales and a coarse tonotopic organization at larger spatial scales (for further details, see [7]). Scale bar 10um. B) Fractional changes in fluorescence measured from a single imaging site in layer 2/3 and a second imaging site from layer 4 of the same column illustrates the shift from homogeneous to heterogenous frequency tuning between the thalamic input layers and superficial layers (for further details, see [75]. The precise low-resolution tonotopy observed with microelectrode recordings from layer 4 (Fig. 1c) is therefore well matched with the coarse tonotopy over large spatial scales in layer 2/3 (Fig. 2a) and the similar frequency tuning organization within local layer 4 ensembles (Fig. 2a, bottom). C) The bandwidth and center frequency of Ca2+ response-based sound tuning between neighboring spines on a single dendrite are highly heterogenous. Cartoons depict dendritic segments from four layer 2/3 neurons, with numbers indicating the effective range of tone frequencies for each spine. Narrowly tuned and widely tuned spines are indicated by red and blue dots, respectively. D) Plot of the distance between neighboring sound-responsive spines versus their best frequency (for further details, see [67]).