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. 2014 Aug 8;345(6197):660-5.
doi: 10.1126/science.1254126.

Selective attention. Long-range and local circuits for top-down modulation of visual cortex processing

Siyu Zhang  1 , Min Xu  1 , Tsukasa Kamigaki  1 , Johnny Phong Hoang Do  1 , Wei-Cheng Chang  1 , Sean Jenvay  1 , Kazunari Miyamichi  2 , Liqun Luo  2 , Yang Dan  3
Affiliations

Selective attention. Long-range and local circuits for top-down modulation of visual cortex processing

Siyu Zhang et al. Science. .

Abstract

Top-down modulation of sensory processing allows the animal to select inputs most relevant to current tasks. We found that the cingulate (Cg) region of the mouse frontal cortex powerfully influences sensory processing in the primary visual cortex (V1) through long-range projections that activate local γ-aminobutyric acid-ergic (GABAergic) circuits. Optogenetic activation of Cg neurons enhanced V1 neuron responses and improved visual discrimination. Focal activation of Cg axons in V1 caused a response increase at the activation site but a decrease at nearby locations (center-surround modulation). Whereas somatostatin-positive GABAergic interneurons contributed preferentially to surround suppression, vasoactive intestinal peptide-positive interneurons were crucial for center facilitation. Long-range corticocortical projections thus act through local microcircuits to exert spatially specific top-down modulation of sensory processing.

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Figures

Fig. 1
Fig. 1. Cg projects to visual cortex and superior colliculus (SC)
(A) Schematic of Cg projections. Dashed lines, locations of coronal sections shown in this figure: (1), Cg; (2), V1; (3), SC. (B to D) Retrograde tracing. (B) Left, Fluorescence image at location (2) showing Retrobeads (green) injected into V1. Arrowhead, injection site. Red, Nissl staining. Right, labeled neurons (dots) at (1), in region outlined by black rectangle (inset). (C) Fluorescence image for red square in (B). Arrowheads, labeled neurons. (D) Similar to (B), with Retrobeads injected into SC. (E) Anterograde tracing from Cg. Left, Fluorescence image at (1). Arrowhead, AAV injection site; middle and right, Cg projections to V1 and SC. SCs/SCm, sensory/motor related SC.
Fig. 2
Fig. 2. Cg activation enhances V1 neuron responses and improves visual discrimination
(A) Schematic of experiment. (B) Cg neuron spiking induced by laser (5 ms/pulse, 10 Hz, blue dots). Upper, example trace. Lower, raster plot. (C) Visual response of a V1 neuron with (blue) or without (black) Cg activation. Left and middle, raster plots and PSTHs at preferred and non-preferred orientations. Black bar, duration of visual stimulation (4 s). Right, orientation tuning of this neuron. Error bar, ±SEM. (D) Population average of orientation tuning, with each neuron normalized and aligned by its optimal orientation without laser. Left and middle, tuning with (blue) and without (black) Cg activation in anesthetized and awake mice. Right, tuning with (green) and without (black) Cg inactivation in awake mice. (E) Modulation factors. Cg activation: anesthetized, 0.24 ± 0.05 (mean ± SEM), P = 10−4 (t-test), n = 38; awake, 0.19 ± 0.04, P = 6×10−5, n = 26; Cg inactivation: awake, −0.12 ± 0.03, P = 0.003, n = 20. Each circle represents one neuron. (F) Effect of Cg activation on visual discrimination performance. Left, an example mouse. Each pair of circles represent d′ measured in one day (n = 11 days). Laser-on (blue), 2.27 ± 0.16 (mean ± SEM.), laser-off (black), 1.91 ± 0.16, P = 0.005, paired t-test. Right, population summary of laser-induced change in d′, for Cg activation (mice injected with AAV2/2-CaMKIIα-hChR2(H134R)-EYFP, 0.30 ± 0.04, n = 5) and control (AAV2/2-CaMKIIα-mCherry, −0.02 ± 0.04, n = 3) groups. Plaser = 0.002, Pgroup = 0.59, Pinteraction = 0.0009 (two-way mixed ANOVA); laser had significant effect only in ChR2 group (P = 0.0006, post-hoc Tukey’s test).
Fig. 3
Fig. 3. Focal activation of Cg axons induces center-surround modulation
(A) Schematic of experiment. (B) Laser stimulation sites (blue) relative to recording site (red, DiI labeling). Green, Cg axons. (C) Average tuning curves with (blue) and without (black) laser at 0 μm (n = 152) and 200 μm (n = 78) from recorded neuron. Error bar, ±SEM. (D) Peak firing rate with vs. without laser for neurons with peak rates < 10 spikes s−1. Inset, for peak rates > 10 spikes s−1. Laser induced significant increase at 0 μm (P = 2×10−10, paired t-test) and decrease at 200 μm (P = 3×10−5). (E) Modulation factor vs. stimulation location. At 0 μm, 0.17 ± 0.02 (mean ± SEM), P = 4×10−16, n = 152; 100 μm, 0.08 ± 0.05, P = 0.11, n = 20; 200 μm, −0.15 ± 0.03, P = 4×10−6, n = 78; 300 μm, −0.02 ± 0.05, P = 0.66, n = 18; 400 μm, 0.04 ± 0.02, P = 0.06, n = 66.
Fig. 4
Fig. 4. Contributions of PV+, SOM+ and VIP+ neurons to disynaptic inhibition and top-down modulation
(A) Schematic of slice experiment. Thunderbolt denotes laser stimulation. (B) Left, normalized IPSC charge vs. blue light location with (green) or without (blue) PV+ neuron inactivation. Reduction of IPSC was found at 0 μm (P = 0.004, n = 9), 200 μm (P = 5×10−5) and 400 μm (P = 0.009). Inset, yellow laser suppressed firing of depolarization-induced PV+ neuron firing (top, membrane potential; yellow bar, yellow laser duration; bottom, current injection. Scale bars, 0.5 s, 20 mV/500 pA). Middle and right, inactivation of SOM+ (n = 10; 0 μm, P = 0.04; 200 μm, P = 7×10−4; 400 μm, P = 0.04) and VIP+ (n = 9; 0 μm, P = 0.02; 200 μm, P = 0.92; 400 μm, P = 0.81) neurons. (C) Schematic of in vivo experiment. (D) Modulation factor vs. location of Cg axon stimulation with (green) or without (cyan) PV+, SOM+ or VIP+ neuron inactivation (n ≥ 16 for each point). PV+ inactivation, 0 μm, P = 0.005; 200 μm, P = 6×10−4; 400 μm, P = 5×10−4. SOM+ inactivation, 0 μm, P = 2×10−4; 200 μm, P = 1×10−8; 400 μm, P = 0.02. VIP + inactivation, 0 μm, P = 5×10−5; 200 μm, P = 0.34; 400 μm, P = 0.59. Yellow circles, modulation factor with yellow light only. (E) Changes in modulation factor (cyan) and normalized IPSC charge (blue) induced by yellow light. (F) Diagrams of V1 circuits recruited by Cg projection. Left, focal activation; right, general activation. Thunderbolt denotes site of Cg axon activation. Black lines, connections important for top-down modulation; line width represents amplitude of synaptic input. Dashed gray lines, other known connections.
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