Abstract
Experience-driven synaptic plasticity in the lateral amygdala is thought to underlie the formation of associations between sensory stimuli and an ensuing threat. However, how the central amygdala participates in such a learning process remains unclear. Here we show that PKC-δ-expressing central amygdala neurons are essential for the synaptic plasticity underlying learning in the lateral amygdala, as they convey information about the unconditioned stimulus to lateral amygdala neurons during fear conditioning.
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Acknowledgements
We thank G.D. Stuber for helping with the in vivo imaging experiments. We thank G.D. Stuber and J. Johansen for critically reading an earlier version of the manuscript, G.-R. Hwang for technical assistance and members of the Li laboratory for helpful discussions. This work was supported by grants from the National Institutes of Health (NIH) (R01MH101214, B.L.), Human Frontier Science Program (RGP0015/2016, B.L.), NARSAD (23169, B.L., and 21227, S.A.), National Natural Science Foundation of China (81428010, B.L. and M.H., and 91432106, M.H.), China Postdoctoral Science Foundation (2016M590316, L.G.), Louis Feil Trust (B.L.), the Stanley Family Foundation (B.L.), Simons Foundation (344904, B.L.) and Wodecroft Foundation (to B.L.).
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K.Y. and B.L. conceived and designed the study. K.Y., S.A., X.Z. and H.S. conducted experiments (X.Z. performed the experiments in which LA neurons were imaged; S.A. and H.S. performed the experiments in which synaptic plasticity in LA neurons was examined; K.Y. conducted most of the remaining experiments). K.Y., X.Z., S.A. and H.S. analyzed data. C.R., L.F. and K.D. developed the intersectional viral strategy and provided critical reagents. F.Z. and M.-H.L. developed the H129-G4 viral system and performed the anterograde tracing with it. L.G. and M.H. performed imaging with the STPT. P.Z. and L.P. developed and assisted with the imaging analysis methods (CNMF and CNMF-E). B.L. wrote the paper with inputs from all authors.
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Supplementary Text and Figures
Supplementary Figures 1–18
Supplementary Video 1
Extraction of the spatial and temporal components of neuronal activity from GCaMP6 signals in PKC-(+ CeL neurons imaged through GRIN lenses.Shown are videos of GCaMP6 signals from PKC-(+ CeL neurons in a representative mouse undergoing fear conditioning. These videos are short clips of movies stitched together, with each clip representing a trial (the onset of which is denoted by each of the solid black lines in the bottom right panel). These videos are played in synchrony, and represent the following contents: “raw data”, GCaMP6 signals without any processing; “background”, the background components in the raw data approximated with our model; “raw–background”, the remaining signals after subtraction of the background from the raw data; “denoised”, the denoised and deconvolved spatiotemporal activity for each neuron obtained from the “raw–background” signals using the CNMF-E; “residual”, the remaining signals. In the “denoised” video, the contours of 5 representative neurons are traced and numbered. The temporal activities of these 5 neurons are displayed in the bottom right panel, in which the moving line indicates the passage of time synchronized with all the videos; the stationary solid black lines denote the onsets of trials (and thus the junctions between the short movie clips); the dashed blue lines denote the onsets of CS; and the dashed red lines denote the onsets of US. Neurons #1-3 are shock-responsive neurons, whereas neurons #4 & 5 only show spontaneous activities. Of note, these denoised and deconvolved signals from adjacent neurons (e.g., #2 and #4) are easily separable. The scale bar beside each of the videos denotes (F values. See Methods for a more detailed description
Supplementary Video 2
Extraction of the spatial and temporal components of neuronal activity from GCaMP6 signals in LA neurons imaged through GRIN lenses. Description: Shown are videos of GCaMP6 signals from LA neurons in a representative mouse receiving tail shocks. These videos are short clips of movies stitched together, with each clip representing a trial (the onset of which is denoted by each of the solid black lines in the bottom right panel). These videos are played in synchrony, and represent the following contents: “raw data”, GCaMP6 signals without any processing; “background”, the background components in the raw data approximated with our model; “raw–background”, the remaining signals after subtraction of the background from the raw data; “denoised”, the denoised and deconvolved spatiotemporal activity for each neuron obtained from the “raw–background” signals using the CNMF-E; “residual”, the remaining signals. In the “denoised” video, the contours of 3 representative neurons are traced and numbered. The temporal activities of these 3 neurons are displayed in the bottom right panel, in which the moving line indicates the passage of time synchronized with all the videos; the stationary solid black lines denote the onsets of trials (and thus the junctions between the short movie clips); and the dashed red lines denote the onsets of shocks. Neurons #1 & 2 are shock-responsive neurons, whereas neurons #3 only shows spontaneous activities. Of note, these denoised and deconvolved signals from adjacent neurons are easily separable. For example, the signals from neuron #1 & 2 are not contaminated by signals from the adjacent neurons, which have high levels of spontaneous activities. The scale bar beside each of the videos denotes (F values. See Methods for a more detailed description.Shown are videos of GCaMP6 signals from LA neurons in a representative mouse receiving tail shocks. These videos are short clips of movies stitched together, with each clip representing a trial (the onset of which is denoted by each of the solid black lines in the bottom right panel). These videos are played in synchrony, and represent the following contents: “raw data”, GCaMP6 signals without any processing; “background”, the background components in the raw data approximated with our model; “raw–background”, the remaining signals after subtraction of the background from the raw data; “denoised”, the denoised and deconvolved spatiotemporal activity for each neuron obtained from the “raw–background” signals using the CNMF-E; “residual”, the remaining signals. In the “denoised” video, the contours of 3 representative neurons are traced and numbered. The temporal activities of these 3 neurons are displayed in the bottom right panel, in which the moving line indicates the passage of time synchronized with all the videos; the stationary solid black lines denote the onsets of trials (and thus the junctions between the short movie clips); and the dashed red lines denote the onsets of shocks. Neurons #1 & 2 are shock-responsive neurons, whereas neurons #3 only shows spontaneous activities. Of note, these denoised and deconvolved signals from adjacent neurons are easily separable. For example, the signals from neuron #1 & 2 are not contaminated by signals from the adjacent neurons, which have high levels of spontaneous activities. The scale bar beside each of the videos denotes (F values. See Methods for a more detailed description
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Yu, K., Ahrens, S., Zhang, X. et al. The central amygdala controls learning in the lateral amygdala. Nat Neurosci 20, 1680–1685 (2017). https://doi.org/10.1038/s41593-017-0009-9
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DOI: https://doi.org/10.1038/s41593-017-0009-9
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