A Feedforward Inhibitory Circuit Mediates Lateral Refinement of Sensory Representation in Upper Layer 2/3 of Mouse Primary Auditory Cortex

Abstract

Sensory information undergoes ordered and coordinated processing across cortical layers. Whereas cortical layer (L) 4 faithfully acquires thalamic information, the superficial layers appear well staged for more refined processing of L4-relayed signals to generate corticocortical outputs. However, the specific role of superficial layer processing and how it is specified by local synaptic circuits remains not well understood. Here, in the mouse primary auditory cortex, we showed that upper L2/3 circuits play a crucial role in refining functional selectivity of excitatory neurons by sharpening auditory tonal receptive fields and enhancing contrast of frequency representation. This refinement is mediated by synaptic inhibition being more broadly recruited than excitation, with the inhibition predominantly originating from interneurons in the same cortical layer. By comparing the onsets of synaptic inputs as well as of spiking responses of different types of neuron, we found that the broadly tuned, fast responding inhibition observed in excitatory cells can be primarily attributed to feedforward inhibition originating from parvalbumin (PV)-positive neurons, whereas somatostatin (SOM)-positive interneurons respond much later compared with the onset of inhibitory inputs to excitatory neurons. We propose that the feedforward circuit-mediated inhibition from PV neurons, which has an analogous function to lateral inhibition, enables upper L2/3 excitatory neurons to rapidly refine auditory representation.

Balance of Excitation and Inhibition

“…For example, for orientation tuning in the mouse visual cortex, the tuning curves of PV cells were found to be much wider than of the principal cells, explaining the wide tuning of inhibitory inputs of pyramidal neurons (Atallah et al 2012). In the auditory cortex the PV cells were found to be tuned for frequency, again consistent with inhibitory inputs to pyramidal cells originating in the neighboring PV neurons (Moore and Wehr 2013;Li et al 2014).…”

Auditory cortex controls sound-driven innate defense behaviour through corticofugal projections to inferior colliculus

“…Recordings from L5 neurons were mostly based on the travel distance of the pipette beneath the pial surface, and verified by histology in some experiments with fluorescence dextran marking, as we described previously19214445. In addition, it is known that ChR2 in the Rpb4-Cre line would be expressed specifically in L5 neurons.…”

Cross-Modality Sharpening of Visual Cortical Processing through Layer-1-Mediated Inhibition and Disinhibition

“…The effect was dependent on the sound intensity. The minimum test intensity at which there was a significant increase in L1 responses was 60 dB SPL (Figure S6B), while the intensity threshold of A1 neurons was lower than 40 dB SPL (Li et al, 2014; Liu et al, 2007; Sun et al, 2013). The largest increase occurred when the maximum test intensity (80 dB SPL) was applied (Figure S6B).…”