Implications of dominant inhibition of LR neurons from neighboring FS cells
In contrast to the lack of local connectivity of LR cells, there is dense connectivity between FS cells and their neighboring excitatory neurons, with the probability of FS-to-LR connectivity reaching 52% (Figure 6), higher than that reported in other regions of the neocortex. For example, connectivity probabilities between FS and pyramidal neurons in superficial layers of the mouse visual cortex was reported as roughly 35%, of the rat visual cortex as 46.5%, of the mouse somatosensory cortex as only 19%, and of the rat barrel cortex as 44% (Beierlein et al., 2003; Jiang et al., 2015; Packer and Yuste, 2011; Yoshimura and Callaway, 2005). This, coupled with the complete lack of local excitatory connections onto LR cells (0%; Figure 6), indicates that the superficial layers of the RSG are a network dominated by strong local inhibition. Therefore, the activity of LR neurons in the superficial RSG is likely to be strongly influenced by feedforward inhibition from neighboring FS neurons.
In strong concordance with our results, a recent study quantifying the response of pyramidal neurons in the superficial RSD to contralateral stimulation has shown that layer 2/3 is characterized by inhibition-dominated feed-forward dynamics (Geijo-barrientos et al., 2019; Sempere-Ferràndez et al., 2018). Also, in response to photostimulation of subicular axons which project extensively to layer 3 of the RSC, the firing of superficial pyramidal neurons is dominated by strong feed-forward inhibition coming from local interneurons (Corcoran et al., 2018). Therefore, similar to the other cortical regions (Avermann et al., 2012; Mateo et al., 2011), the superficial RSG could implement a sparse neuronal code dominated by local inhibition from interneurons. Given the well-known role of the RSC in memory and spatial navigation related functions, such sparse population codes can greatly boost the pattern storage and recognition capabilities of the system (Marr, 1971). Indeed, sparse neuronal codes representing sequential, place-cell like firing have been reported in the neurons of the superficial RSC during spatially-guided movements (Mao et al., 2017). Our results start to explain how the local cells and circuitry of the superficial retrosplenial cortex can support these unique computational functions.