A Disinhibitory Circuit for Contextual Modulation in Primary Visual Cortex

Abstract

Context strongly guides perception by influencing the saliency of sensory stimuli. Accordingly, sensory neurons respond differently to the same stimulus depending on the context in which the stimulus is embedded. In the visual system, the relationship between the features of the stimulus and those of the surround determine how excitatory neurons are modulated. Their responses are suppressed when center and surround share the same features but not when they are different. The mechanisms that relieve surround suppression and thereby generate contextual modulation remain unclear. Here we show that the disinhibitory circuit consisting of somatostatin-expressing (SOM) and vasoactiveintestinal-peptide-expressing (VIP) inhibitory neurons contextually modulates excitatory neurons in mouse primary visual cortex. When the stimulus and the surround share the same features, VIP neurons are inactive and SOM neurons can suppress excitatory neurons. However, when the features of the stimulus differ from those of the surround, VIP neurons are activated, thereby inhibiting SOM neurons and relieving excitatory neurons from suppression. Optogenetic silencing of VIP neurons, via disinhibition of SOM neurons, reduces the contextual modulation of excitatory neurons. We have identified a canonical cortical disinhibitory circuit which contributes to contextual modulation of excitatory neurons, and may thereby regulate perceptual saliency.

Distinct organization of two cortico-cortical feedback pathways

“…In contrast, the activity of V1 neurons is suppressed if both feed-forward and feedback are driven by one feature (e.g. a uniform stimulus with large size), which is likely mediated by SOM+ cells, given the connectivity pattern we found and their size tuning properties 41,45 . However, future work is needed to directly examine the structure-function connectivity rules between LM and V1 neurons.…”

“…Since we found both excitation and inhibition on V1 principal cells, our finding is compatible with both hypotheses, depending on the specificity of the excitatory connections between LM and V1 principal neurons. Two recent studies 37,45 seem to provide evidence that LM to V1 feedback is more consistent with the predictive coding model 66 . Marques et al 37 reveals that LM to V1 feedback innervates locations in V1 that would be activated by stimuli orthogonal to or opposite to a cell's own tuning, while Keller et al 45 shows that V1 neurons are more likely to be innervated by the LM boutons whose receptive fields are offset from those of the V1 neurons.…”

“…Instead, feedback from LM to V1 exhibited an opposite pattern with stronger connections to SOM+ cells compared to VIP+ cells, which, to our knowledge, is the first study that shows SOM+ cells are strongly activated by top-down feedback projections. Previous studies have revealed that SOM+ cells are involved in surround suppression because their activities increase with the stimulus size 41,42 , and studies in both primates 43,44 and rodents 45,46 reveal that feedback from the higher visual area contributes to surround suppression. Our finding here filled in this gap by showing that feedback from LM to V1 recruits local SOM+ interneurons.…”

Ontogeny of the VIP+ interneuron sensory-motor circuit prior to active whisking

“…Moreover our mapping of the efferent targets of VIP+ IN reinforce the body of evidence showing that this class of neuron target pyramidal cells directly (Chiu et al, 2018;Garcia-Junco-Clemente et al, 2017;Lee et al, 2013;Pfeffer et al, 2013) and do so from an early age. As such VIP+ INs are, from the moment that they integrate into neocortex, well positioned to exert varied effects as described in the juvenile and adult cortex (Batista-Brito et al, 2017;Bigelow et al, 2019;Cardin, 2019;Dipoppa et al, 2018;Fu et al, 2014;Garrett et al, 2020;Keller et al, 2020;Millman et al, 2019;Pakan et al, 2016;Pi et al, 2013).…”

Common rules underlying optogenetic and behavioral modulation of responses in multi-cell-type V1 circuits

“…The inhibitory sub-circuit is composed of multiple elements with three types -parvalbumin-(PV), somatostatin-(SOM), and vasoactive-intestinal-peptide (VIP) expressing cells that constitute 80% of GABAergic interneurons in the mouse primary visual cortex (V1) 8 . These inhibitory cell types do not act in unison, but differentially contribute to response tuning [9][10][11][12] and to contextual [13][14][15][16][17] and behavioral-state modulations [18][19][20][21] . In particular, two of these types, SOM and VIP, engage in competitive dynamics whose outcome directly regulates pyramidal cell activity via inhibition or disinhibition.…”