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A disinhibitory circuit mediates motor integration in the somatosensory cortex

Nature Neuroscience volume 16, pages 1662–1670 (2013)Cite this article

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Abstract

The influence of motor activity on sensory processing is crucial for perception and motor execution. However, the underlying circuits are not known. To unravel the circuit by which activity in the primary vibrissal motor cortex (vM1) modulates sensory processing in the primary somatosensory barrel cortex (S1), we used optogenetics to examine the long-range inputs from vM1 to the various neuronal elements in S1. We found that S1-projecting vM1 pyramidal neurons strongly recruited vasointestinal peptide (VIP)-expressing GABAergic interneurons, a subset of serotonin receptor–expressing interneurons. These VIP interneurons preferentially inhibited somatostatin-expressing interneurons, neurons that target the distal dendrites of pyramidal cells. Consistent with this vM1-mediated disinhibitory circuit, the activity of VIP interneurons in vivo increased and that of somatostatin interneurons decreased during whisking. These changes in firing rates during whisking depended on vM1 activity. Our results suggest previously unknown circuitry by which inputs from motor cortex influence sensory processing in sensory cortex.

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Figure 1: Long-range excitatory inputs from vM1 to different types of neurons in the superficial layers of S1.
Figure 2: VIP interneurons receive the strongest input from vM1.
Figure 3: VIP interneurons most strongly inhibit SST interneurons in S1 superficial layers.
Figure 4: VIP interneurons mediate disynaptic feedforward inhibition of SST interneurons following vM1 activation.
Figure 5: Spiking activity of VIP interneurons and SST interneurons in superficial layers of S1 during active whisking.
Figure 6: vM1 activity is responsible for the increased activity of VIP interneurons and decreased activity of SST interneurons in S1 during whisking.

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Acknowledgements

We thank all of the members of the Rudy and Fishell laboratories for helpful discussions. We thank K. Deisseroth (Stanford University) for DIO-ChR2-mCherry plasmids, Z. Talbot for help with intrinsic imaging and setting-up a camera for whisking behavior, and E. Merriam for advice on in vivo data analysis. This work was supported by grants from the US National Institutes of Health (R01 NS30989 and P01 NS074972 to B.R., MH071679 and P01 NS074972 to G.F., and 1F32NS076316 to S.L.). I.K. was supported by Epilepsy Foundation grant 260691.

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Authors and Affiliations

  1. Department of Neuroscience and Physiology, New York University Neuroscience Institute, Smilow Research Center, New York University School of Medicine, New York, New York, USA

    Soohyun Lee, Illya Kruglikov, Gord Fishell & Bernardo Rudy

  2. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA

    Z Josh Huang

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Contributions

S.L., G.F. and B.R. conceived the study. S.L. conducted all of the ChR2 and NpHR experiments and analysis. I.K. conducted local input experiments and analysis, and set up two-photon targeted in vivo recordings. S.L. and I.K. performed in vivo experiments. Z.J.H. provided Vip-cre and Sst-cre mice. S.L., I.K., G.F. and B.R. wrote the paper.

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Correspondence to Soohyun Lee or Bernardo Rudy.

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Integrated supplementary information

Supplementary Figure 1 Expression of ChR2-mCherry in vM1 pyramidal neurons.

(a) Schematics of virus injection. (b) Representative voltage response to brief photo-stimulation (LED, 470 nm, 5 ms, blue bars) in a current-clamped pyramidal neuron expressing ChR2mCherry (inset). (c) Voltage traces showing spikes recorded from a current-clamped vM1 pyramidal neuron which expressed ChR2 evoked by 5, 10, 20, 40 and 100 Hz trains of photo-stimulation (blue trace). (d) Spiking probability evoked by the trains of photo-stimulation. e, Jitter of spike times throughout the train of photo-stimulation (n = 7). Jitter of spike times was calculated as the standard deviation of spike latencies. Spike latency was measured from the onset of the photo-stimulation to the onset of the spike. Photo-stimulations which failed to elicit a spike are not included.

Supplementary Figure 2 Resting membrane potentials and membrane input resistance of four different groups of neurons in S1 superficial layers.

(a-b) Four groups of neurons have different resting membrane potentials (a), and input resistances (b). Solid colored horizontal bars indicate mean values. Statistical significance according to t-test is indicated by *** p<0.0005.

Supplementary Figure 3 Synaptic dynamics of responses to photo-stimulation of vM1 inputs in SST interneurons and pyramidal neurons in S1.

(a) Train of photo-stimuli (40 Hz) evoked facilitating EPSCs from a SST IN (top) and depressing EPSCs from a pyramidal neuron (middle). Lower panel shows overlap of these two traces for direct comparison. Gray traces indicate Individual sweeps; colored traces indicate average (blue, SST IN; black, pyramidal neurons). Blue traces indicate photo-stimulation (LED, 470 nm, 5 ms) delivered at 40 Hz. (b) Population data of synaptic dynamics of SST INs (blue, n=8) and pyramidal neurons (black, n=10) to photo-stimulation of vM1 inputs. Mean SEM. For each neuron, amplitude of EPSCs is normalized to 1st ESPC. Wilcoxon signed rank test, ** p<0.005.

Supplementary Figure 4 Latency of photo-stimulation evoked EPSCs among different groups of neurons in S1.

(a) Latency of EPSCs to photo-stimulation of vM1 axons. (b) Latency of IPSCs to photo-stimulation of VIP INs. Solid colored bars indicate mean values. Spike latency was measured from the onset of the photo-stimulation to the onset of the spike. Every pair-wise comparison showed no statistical significance.

Supplementary Figure 5 Expression of ChR2-mCherry in VIP interneurons in S1.

(a) Laminar distribution of ChR2mCherry expressing VIP INs in S1. ChR2mCherry expressing VIP INs are mostly localized in superficial layers. The inset shows the dense neuronal process of ChR2mCherry expressing VIP INs in layer 1. Scale bar = 100μm. (b) Schematics of AAV-DIO-ChR2mCherry injection into superficial layers of VIP-Cre mice.

Supplementary Figure 6 Local excitatory inputs to VIP and PV interneurons.

(a) Schematic drawing of the experimental design. (b) Simultaneous whole cell recordings in current-clamp mode from an FS interneuron and a nearby pyramidal cell. Left, representative examples of a firing pattern for each cell type. Right, two EPSPs at 20 Hz recorded in both cells, produced by a near threshold electrical stimulation delivered through a laterally positioned bipolar concentric electrode. (c) Same as in b but for the pairs of VIP interneurons and pyramidal cells. (d) Summary data on EPSP amplitudes in FS (n = 7) and VIP (n = 8) interneurons normalized to the EPSP amplitude simultaneously recorded in a nearby pyramidal cell. **p<0.01, * p<0.05 paired Student's t-test.

Supplementary Figure 7 Schematic illustration of how vM1 inputs modulate S1 activity.

During non-whisking awake periods SST INs in S1 are spontaneously active and thus shunt the dendritic domain of pyramidal cells. During active whisking, i.e., neuronal activity of vM1 is elevated, excitatory inputs from vM1 strongly activate VIP INs, a subgroup of 5HT3aR INs in S1 superficial layers. VIP INs, in turn, provide strong feedforward inhibition to SST INs, thus disinhibiting the distal dendrites of pyramidal neurons. Disinhibition of the dendritic domain of the pyramidal neurons allows dendritic activity to amplify sensory information arriving to the proximal and basal dendrites of pyramidal cells.

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Lee, S., Kruglikov, I., Huang, Z. et al. A disinhibitory circuit mediates motor integration in the somatosensory cortex. Nat Neurosci 16, 1662–1670 (2013). https://doi.org/10.1038/nn.3544

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