NDNF interneurons in layer 1 gain-modulate whole cortical columns according to an animal’s behavioral state

Title: NDNF interneurons in layer 1 gain-modulate whole cortical columns according to an animal’s behavioral state

Journal: Neuron (2021) 109(13):2150-2164

Link: https://www.sciencedirect.com/science/article/pii/S0896627321003275?via%3Dihub

Comments: Processing of sensory information in neural circuits is modulated by an animal’s behavioral state, but the underlying cellular mechanisms are not well understood. Focusing on the mouse visual cortex, the authors analyze the role of GABAergic interneurons that are located in layer 1 and express Ndnf (L1 NDNF INs) in the state dependent control over sensory processing.

They combine subtype-specific genetic tools and approaches with in vivo two-photon (2P) imaging, pupillometry, viral tracing, electrophysiology ex vivo and in vivo, chemogenetics, and optogenetics to investigate the role of L1 NDNF INs in the processing of visual information in the mouse primary visual cortex (V1). Result shows (1) that these INs respond to visual stimuli in a cell-type-specific manner, as they are orientation tuned, are modulated only moderately by stimulus size and spatial frequency and are driven rather uniformly across varying stimulus contrasts; (2) that their spontaneous activity and sensory evoked responses are strongly enhanced when an animal is aroused; (3) that they receive long-range inputs from multiple brain regions that can convey sensory-driven bottom-up inputs and behavioral state-dependent top-down inputs; (4) that they can provide direct, long-lasting divisive inhibition to local excitatory neurons across all cortical layers, probably via their apical dendrites; (5) that in parallel to this long-lasting dendritic inhibition, L1 NDNF INs disinhibit the somata of visual cortex excitatory neurons by directly inhibiting FS PV INs; and (6) that the net effect of this state-dependent dendritic inhibition and somatic disinhibition by L1 NDNF INs is a gain modulation in the visually evoked responses of excitatory neurons across all layers of V1 and an increase in the SNR of their visually evoked responses. At times of high arousal, the topdown-mediated activation of L1 NDNF INs leads to a relative shift of inhibition from the soma toward the apical dendrites in excitatory neurons across all cortical layers and that this improves the SNR upon bottom-up sensory stimulation.

Previous study show SST INs can directly inhibit L1 NDNF INs, it seems more likely that the inhibition conveyed by these two IN subtypes to specific dendritic branches serves different biological purposes and thereby rather complement each other than compete with each other. Thus, they point out that, future experiments will have to clarify how L1 NDNF INs and SST INs affect each other’s activity in the visual cortex of awake mice and how this, in turn, affects inhibition and visually evoked responses in specific branches of excitatory neuron tuft dendrites.