Transient Subgranular Hyperconnectivity to L2/3 and Enhanced Pairwise Correlations During the Critical Period in the Mouse Auditory Cortex

Abstract

During the critical period, neuronal connections are shaped by sensory experience. While the basis for this temporarily heightened plasticity remains unclear, shared connections introducing activity correlations likely play a key role. Thus, we investigated the changing intracortical connectivity in primary auditory cortex (A1) over development. In adult, layer 2/3 (L2/3) neurons receive ascending inputs from layer 4 (L4) and also receive few inputs from subgranular layer 5/6 (L5/6). We measured the spatial pattern of intracortical excitatory and inhibitory connections to L2/3 neurons in slices of mouse A1 across development using laser-scanning photostimulation. Before P11, L2/3 cells receive most excitatory input from within L2/3. Excitatory inputs from L2/3 and L4 increase after P5 and peak during P9–16. L5/6 inputs increase after P5 and provide most input during P12–16, the peak of the critical period. Inhibitory inputs followed a similar pattern. Functional circuit diversity in L2/3 emerges after P16. In vivo two-photon imaging shows low pairwise signal correlations in neighboring neurons before P11, which peak at P15–16 and decline after. Our results suggest that the critical period is characterized by high pairwise activity correlations and that transient hyperconnectivity of specific circuits, in particular those originating in L5/6, might play a key role.

Transient coupling between subplate and subgranular layers to L1 neurons before and during the critical period

“…In vitro Laser-Scanning Photostimulation (LSPS): LSPS experiments were performed as previously described (Meng et al, 2015;Meng et al, 2019;Meng et al, 2017b;Viswanathan et al, 2017).…”

“…Stimuli were applied at 0.5 -1 Hz. Analysis was performed essentially as described previously with custom software written in MATLAB (Meng et al, 2014;Meng et al, 2015Meng et al, , 2017aMeng et al, 2019;Meng et al, 2017b). Activation profiles of neurons across cortical layers during these ages show that LSPS resolution does not vary .…”

“…To detect monosynaptically evoked postsynaptic currents (PSCs), we detected PSCs with onsets in an approximately 50-ms window after the stimulation. This window was chosen based on the observed spiking latency under our recording conditions (Meng et al, 2015;Meng et al, 2019;Meng et al, 2017b;Viswanathan et al, 2017). Our recordings are performed at room temperature and in high-Mg 2+ solution to reduce the probability of polysynaptic inputs.…”

“…We measured both peak amplitude and transferred charge; transferred charge was measured by integrating the PSC. While the transferred charge might include contributions from multiple events, our prior studies showed a strong correlation between these measures (Meng et al, 2014;Meng et al, 2015;Meng et al, 2019;Viswanathan et al, 2012). Traces containing a short-latency (< 8 ms) 'direct' response were discarded from the analysis (black patches in color-coded maps) as were traces that contained longer latency inward currents of long duration (> 50 ms).…”

“…Morphology: Biocytin-filled cells were processed as reported previously (Deng et al, 2017;Meng et al, 2019;Sheikh et al, 2019;Zhao et al, 2009). Cells filled with biocytin were stained and reconstructed (Neurolucida Ver.…”