Spatial clustering of inhibition in mouse primary visual cortex

Abstract

Whether mouse visual cortex contains orderly feature maps is debated. The overlapping pattern of geniculocortical (dLGN) inputs with M2 muscarinic acetylcholine receptor-rich patches in layer 1 (L1) suggests a non-random architecture. Here, we found that L1 inputs from the lateral posterior thalamus (LP) avoid patches and target interpatches. Channelrhodopsin-assisted mapping of EPSCs in L2/3 shows that the relative excitation of parvalbumin-expressing interneurons (PVs) and pyramidal neurons (PNs) by dLGN, LP and cortical feedback are distinct and depend on whether the neurons reside in clusters aligned with patches or interpatches.Paired recordings from PVs and PNs shows that unitary IPSCs are larger in interpatches than patches. The spatial clustering of inhibition is matched by dense clustering of PV-terminals in interpatches. The results show that the excitation/inhibition balance across V1 is organized into patch and interpatch subnetworks which receive distinct long-range inputs and are specialized for the processing of distinct spatiotemporal features. S1), and measured EGFP intensity in patches (top 3 rd ) and interpatches (bottom 3 rd ). We then normalized the pixel values in interpatches to the mean intensity in patches and plotted the counts in different intensity bins. We found that the fluorescence intensity in patches was 2.1 ± 0.024fold (p = 8x10 -18 , Komolgorov-Smirnov test [KS]) higher in patches than interpatches ( Figure 1D). Similar to our previous findings, patches and interpatches in L1 were 60-80 µm wide and their centroids were 120-140 µm apart. dLGN projections to L4, and 5/6 appeared uniform (data not shown). Inputs to L1 from the LP thalamus exhibited a strikingly different pattern, showing 1.6 ± 0.14-fold (p = 1.33x10 -4 , KS) stronger projections to M2-interpatches ( Figure 1E-H).Simultaneous tracing of dLGN and LP inputs with AAV2/1hSyn.tdTomato.WPRE.bGH and AAV2/1.hSyn.EGFP, respectively, confirmed the interdigitating pattern of projections from primary and higher order thalamic nuclei, showing denser LP input to interpatches (p = 7.95 x 10 -4 , KS) ( Figure 1I-M). Clustering of intracortical inputs to L1 of V1We next compared feedback projections from the higher visual cortical ventral stream lateromedial area, LM, to V1 with inputs from the dLGN. Double viral tracings from the dLGN (AAV2/1.hSyn.EGFP) and LM (AAV2/1hSyn.tdTomato.WPRE.bGH) showed that inputs from both sources overlapped in presumtive M2+ patches of L1 ( Figure 1A-C; 2A). Quantitative analysis showed that LM inputs to patches were 1.7 ± 0.05-fold denser than to interpatches (p = 1.45x10 4 , KS) ( Figure 2B). We have shown previously that inputs from the dorsal stream anterolateral area, AL, terminate in M2+ patches (Ji et al., 2015), raising the question whether M2+ patches are the preferred targets of cortical feedback. To address this, we traced the connections to V1 from the posteromedial area, PM, another member of the dorsal stream (Wang et al. 2012). We found that inputs from PM were non-uniform, overlapped i...

The Visual Cortex in Context

“…They hypothesized that this effect was through the LP nucleus but interestingly, in these experiments, the SC modulated the activity in V1 even when the activity in the LP nucleus was suppressed, most likely through the tectogeniculate pathway. Contrary to the locomotion signals that come from LGN, axons from the LP nucleus convey information about the discrepancies between self-motion and external motion (Roth et al 2016), and when compared to the axons from the LGN, they have distinct spatial localization within V1 (Bista et al 2019). Based on connectivity and functional properties, the LP nucleus can be separated into three subregions and it can offer access of frontal areas to visual cortex (Bennett et al 2019).…”

“…It is believed that feedback can dynamically modulate the effective connectivity within V1, allowing neurons to change their functional properties depending on the behavioral context (Gilbert & Li 2013). That can be achieved with a differential recruitment of interneurons: feedback connections both from cortical areas VISlm and VISpm and from the LP nucleus show a balanced input to excitatory and inhibitory cells in V1, whereas feedforward connections from the LGN preferentially recruit parvalbumin (PV) interneurons (Bista et al 2019, D'Souza et al 2016. When activity in the area VISlm is suppressed, it has been shown to selectively decrease the responses of V1 neurons at their prefer orientation (Pafundo et al 2016).…”