Superficial Layers Suppress the Deep Layers to Fine-tune Cortical Coding

Abstract

The descending microcircuit from layer 2/3 (L2/3) to layer 5 (L5) is one of the strongest excitatory pathways in the cortex, presumably forming a core component of its feedforward hierarchy. To date, however, no experiments have selectively tested the impact of L2/3 activity on L5 during active sensation. We used optogenetic, cell-type-specific manipulation of L2/3 neurons in the barrel cortex of actively sensing mice (of either sex) to elucidate the significance of this pathway to sensory coding in L5. Contrary to standard models, activating L2/3 predominantly suppressed spontaneous activity in L5, whereas deactivating L2/3 mainly facilitated touch responses in L5. Somatostatin interneurons are likely important to this suppression because their optogenetic deactivation significantly altered the functional impact of L2/3 onto L5. The net effect of L2/3 was to enhance the stimulus selectivity and expand the range of L5 output. These data imply that the core cortical pathway increases the selectivity and expands the range of cortical output through feedforward inhibition.The primary sensory cortex contains six distinct layers that interact to form the basis of our perception. While rudimentary patterns of connectivity between the layers have been outlined quite extensively in vitro, functional relationships in vivo, particularly during active sensation, remain poorly understood. We used cell-type-specific optogenetics to test the functional relationship between layer 2/3 and layer 5. Surprisingly, we discovered that L2/3 primarily suppresses cortical output from L5. The recruitment of somatostatin-positive interneurons is likely fundamental to this relationship. The net effect of this translaminar suppression is to enhance the selectivity and expand the range of receptive fields, therefore potentially sharpening the perception of space.

A supragranular nexus for the effects of neocortical beta events on human tactile perception

“…Updating our prior model to reflect this hypothesis did not significantly change the robustly observed stereotypical beta event waveform shape (10,12), and was crucial to our conclusions regarding beta event-mediated tactile suppression. Our findings are also in agreement with several studies that have suggested slow inhibition in the supragranular layers -including through GABAB mechanisms -is a key regulator of conscious perception (31,32) and is specifically involved in inhibiting somatosensory perception (33). For example, Larkum and colleagues have shown that dendrite-mediated suppression of rodent somatosensory perception is regulated by GABAB receptor activation in the mid-apical dendrite of L5 pyramidal cells, driven by a transcallosal inhibitory projection (28,34).…”

Deep and superficial layers of the primary somatosensory cortex are critical for whisker-based texture discrimination in mice

“…At a general level, our data are also compatible with this hypothesis. However, the most prominent synergy observed to date showed L2/3 suppresses deep layer activity (Adesnik & Scanziani 2010, Pluta et al 2019, predicting opposite results of deep versus superficial manipulations. We find on the contrary that mice tend to classify textures as rough when either deep or superficial layers are inhibited.…”

“…L2/3 has a strongly suppressive effect on deep layer activity (Adesnik & Scanziani 2010, Pluta et al 2019. Conceivably, strong connections like these could produce local forms of diaschisis, whereby silencing one set of layers does not reveal its task involvement but rather that it disrupts another key set of layers.…”

Modulation of coordinated activity across cortical layers by plasticity of inhibitory synapses onto layer 5 pyramidal neurons

“…The dynamic modulation of PN firing, induced by plasticity of feed-forward inhibition had a powerful effect on the columnar integration of activity across cortical layers. Indeed, activation of layer 2/3 PNs was shown to increase the firing of PNs in layer 5 of the same column (Adesnik and Scanziani, 2010; but see Pluta et al, 2019). LTP of feed-forward inhibition strongly diminished (in fact, on average, it abolished) the layer 2/3-dependent activation of layer 5 PNs, thereby affecting the flow of neuronal communication across cortical layers.…”

“…In principle, feed-forward inhibition can result from long-range recruitment of different interneuron subclasses (Pluta et al, 2019). Yet, potentiation of FFI likely involves perisomatic inhibition originating almost exclusively from PV basket cells.…”