The majority of neurons in primary visual cortex are tuned for stimulus orientation, but the factors that account for the range of orientation selectivities exhibited by cortical neurons remain unclear. To address this issue, we used in vivo two-photon calcium imaging to characterize the orientation tuning and spatial arrangement of synaptic inputs to the dendritic spines of individual pyramidal neurons in layer 2/3 of ferret visual cortex. The summed synaptic input to individual neurons reliably predicted the neuron's orientation preference, but did not account for differences in orientation selectivity among neurons. These differences reflected a robust input–output nonlinearity that could not be explained by spike threshold alone and was strongly correlated with the spatial clustering of co-tuned synaptic inputs within the dendritic field. Dendritic branches with more co-tuned synaptic clusters exhibited greater rates of local dendritic calcium events, supporting a prominent role for functional clustering of synaptic inputs in dendritic nonlinearities that shape orientation selectivity.
Subscribe to Journal
Get full journal access for 1 year
only $4.92 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Goris, R.L., Simoncelli, E.P. & Movshon, J.A. Origin and function of tuning diversity in macaque visual cortex. Neuron 88, 819–831 (2015).
Ringach, D.L., Shapley, R.M. & Hawken, M.J. Orientation selectivity in macaque V1: diversity and laminar dependence. J. Neurosci. 22, 5639–5651 (2002).
Tan, A.Y., Brown, B.D., Scholl, B., Mohanty, D. & Priebe, N.J. Orientation selectivity of synaptic input to neurons in mouse and cat primary visual cortex. J. Neurosci. 31, 12339–12350 (2011).
Schoups, A., Vogels, R., Qian, N. & Orban, G. Practising orientation identification improves orientation coding in V1 neurons. Nature 412, 549–553 (2001).
Ko, H. et al. Functional specificity of local synaptic connections in neocortical networks. Nature 473, 87–91 (2011).
Gilbert, C.D. & Wiesel, T.N. Columnar specificity of intrinsic horizontal and corticocortical connections in cat visual cortex. J. Neurosci. 9, 2432–2442 (1989).
Bosking, W.H., Zhang, Y., Schofield, B. & Fitzpatrick, D. Orientation selectivity and the arrangement of horizontal connections in tree shrew striate cortex. J. Neurosci. 17, 2112–2127 (1997).
Malach, R., Amir, Y., Harel, M. & Grinvald, A. Relationship between intrinsic connections and functional architecture revealed by optical imaging and in vivo targeted biocytin injections in primate striate cortex. Proc. Natl. Acad. Sci. USA 90, 10469–10473 (1993).
Nauhaus, I., Benucci, A., Carandini, M. & Ringach, D.L. Neuronal selectivity and local map structure in visual cortex. Neuron 57, 673–679 (2008).
Priebe, N.J. & Ferster, D. Mechanisms of neuronal computation in mammalian visual cortex. Neuron 75, 194–208 (2012).
Losonczy, A. & Magee, J.C. Integrative properties of radial oblique dendrites in hippocampal CA1 pyramidal neurons. Neuron 50, 291–307 (2006).
Branco, T. & Häusser, M. Synaptic integration gradients in single cortical pyramidal cell dendrites. Neuron 69, 885–892 (2011).
Schiller, J., Major, G., Koester, H.J. & Schiller, Y. NMDA spikes in basal dendrites of cortical pyramidal neurons. Nature 404, 285–289 (2000).
Smith, S.L., Smith, I.T., Branco, T. & Häusser, M. Dendritic spikes enhance stimulus selectivity in cortical neurons in vivo. Nature 503, 115–120 (2013).
Palmer, L.M. et al. NMDA spikes enhance action potential generation during sensory input. Nat. Neurosci. 17, 383–390 (2014).
Lavzin, M., Rapoport, S., Polsky, A., Garion, L. & Schiller, J. Nonlinear dendritic processing determines angular tuning of barrel cortex neurons in vivo. Nature 490, 397–401 (2012).
Kleindienst, T., Winnubst, J., Roth-Alpermann, C., Bonhoeffer, T. & Lohmann, C. Activity-dependent clustering of functional synaptic inputs on developing hippocampal dendrites. Neuron 72, 1012–1024 (2011).
Takahashi, N. et al. Locally synchronized synaptic inputs. Science 335, 353–356 (2012).
Chen, X., Leischner, U., Rochefort, N.L., Nelken, I. & Konnerth, A. Functional mapping of single spines in cortical neurons in vivo. Nature 475, 501–505 (2011).
Chen, T.W. et al. Ultrasensitive fluorescent proteins for imaging neuronal activity. Nature 499, 295–300 (2013).
Jia, H., Rochefort, N.L., Chen, X. & Konnerth, A. Dendritic organization of sensory input to cortical neurons in vivo. Nature 464, 1307–1312 (2010).
Weliky, M., Bosking, W.H. & Fitzpatrick, D. A systematic map of direction preference in primary visual cortex. Nature 379, 725–728 (1996).
Ohki, K. et al. Highly ordered arrangement of single neurons in orientation pinwheels. Nature 442, 925–928 (2006).
Ikezoe, K., Mori, Y., Kitamura, K., Tamura, H. & Fujita, I. Relationship between the local structure of orientation map and the strength of orientation tuning of neurons in monkey V1: a 2-photon calcium imaging study. J. Neurosci. 33, 16818–16827 (2013).
Priebe, N.J. & Ferster, D. Inhibition, spike threshold, and stimulus selectivity in primary visual cortex. Neuron 57, 482–497 (2008).
Carandini, M. & Ferster, D. Membrane potential and firing rate in cat primary visual cortex. J. Neurosci. 20, 470–484 (2000).
Schummers, J., Mariño, J. & Sur, M. Synaptic integration by V1 neurons depends on location within the orientation map. Neuron 36, 969–978 (2002).
Tan, A.Y., Chen, Y., Scholl, B., Seidemann, E. & Priebe, N.J. Sensory stimulation shifts visual cortex from synchronous to asynchronous states. Nature 509, 226–229 (2014).
Mel, B.W., Ruderman, D.L. & Archie, K.A. Translation-invariant orientation tuning in visual “complex” cells could derive from intradendritic computations. J. Neurosci. 18, 4325–4334 (1998).
Poirazi, P., Brannon, T. & Mel, B.W. Pyramidal neuron as two-layer neural network. Neuron 37, 989–999 (2003).
Poirazi, P. & Mel, B.W. Impact of active dendrites and structural plasticity on the memory capacity of neural tissue. Neuron 29, 779–796 (2001).
Poirazi, P., Brannon, T. & Mel, B.W. Arithmetic of subthreshold synaptic summation in a model CA1 pyramidal cell. Neuron 37, 977–987 (2003).
Hofer, S.B. et al. Differential connectivity and response dynamics of excitatory and inhibitory neurons in visual cortex. Nat. Neurosci. 14, 1045–1052 (2011).
Maldonado, P.E., Gödecke, I., Gray, C.M. & Bonhoeffer, T. Orientation selectivity in pinwheel centers in cat striate cortex. Science 276, 1551–1555 (1997).
Gambino, F. et al. Sensory-evoked LTP driven by dendritic plateau potentials in vivo. Nature 515, 116–119 (2014).
Greenberg, D.S., Houweling, A.R. & Kerr, J.N. Population imaging of ongoing neuronal activity in the visual cortex of awake rats. Nat. Neurosci. 11, 749–751 (2008).
Constantinople, C.M. & Bruno, R.M. Effects and mechanisms of wakefulness on local cortical networks. Neuron 69, 1061–1068 (2011).
Sellers, K.K., Bennett, D.V., Hutt, A. & Fröhlich, F. Anesthesia differentially modulates spontaneous network dynamics by cortical area and layer. J. Neurophysiol. 110, 2739–2751 (2013).
Branco, T., Clark, B.A. & Häusser, M. Dendritic discrimination of temporal input sequences in cortical neurons. Science 329, 1671–1675 (2010).
Pologruto, T.A., Sabatini, B.L. & Svoboda, K. ScanImage: flexible software for operating laser scanning microscopes. Biomed. Eng. Online 2, 13 (2003).
Peirce, J.W. PsychoPy–Psychophysics software in Python. J. Neurosci. Methods 162, 8–13 (2007).
Edelstein, A., Amodaj, N., Hoover, K., Vale, R. & Stuurman, N. Computer control of microscopes using microManager. Curr. Protoc. Mol. Biol. Ch. 14, Unit 14 20 (2010).
Nauhaus, I., Nielsen, K.J., Disney, A.A. & Callaway, E.M. Orthogonal micro-organization of orientation and spatial frequency in primate primary visual cortex. Nat. Neurosci. 15, 1683–1690 (2012).
Mardia, K.V. & Jupp, P.E. Directional Statistics (Wiley, West Sussex, UK, 2000).
Kalatsky, V.A. & Stryker, M.P. New paradigm for optical imaging: temporally encoded maps of intrinsic signal. Neuron 38, 529–545 (2003).
The authors would like to thank the GENIE project for providing GCaMP6, D. Ouimet for surgical assistance, and G. Smith and W. Bosking for discussions. The research was supported by NIH grant EY011488 (D.F.) and by the Max Planck Florida Institute for Neuroscience.
The authors declare no competing financial interests.
Integrated supplementary information
(a) Example dendritic fluorescence trace; (b) Raw spine fluorescence trace plotted with predicted bAP component of spine signal; (c) Predicted synaptic signal after subtraction of predicted bAP.
(a) Single calcium events occur and can be restricted to individual spines; scale bar 5 microns; (b) Responses recorded from four spines and adjacent parent dendritic branches illustrating that spine Ca2+ transients occur independent of dendritic events
(a) Cranial window with two-photon FOV indicated by dashed white line, with control points indicated by red dots; Scale bar: 500 μm; (b) Intrinsic imaging orientation preference map; (c): Control point (red dots) placement guided by fiduciary markers; (d) Z-Projection of pia through 30 μm of two-photon z-stack; (e) Local orientation preference map.
Comparison of single spine orientation preference with that of the spine’s location in the orientation preference map across all imaged neurons
Left column shows normalized summed spine responses with threshold applied; responses are aligned to the preferred orientation and Gaussian fit is shown as a dashed line; Middle column shows normalized somatic responses; responses are aligned to the preferred orientation and Gaussian fit is shown as a dashed line; Right column shows the spine-soma input output function, computed as interpolated fits of the spine input versus somatic output
Comparison of spiking with subthreshold orientation selectivity; spiking and subthreshold measurements collected from each neuron are connected by a line
(a) Nearest neighboring spines (n=765) show similar orientation preferences; (b) Apical(n=74) and basal (n= 72) dendritic branches show similar levels of circular dispersion; box boundaries are 25th and 75th percentile values and whiskers are maxima and minima; (c) The circular dispersion values for all branches on each cell are plotted against somatic orientation selectivity; each column of points is a single cell; cells ordered on the x-axis by their orientation selectivity; dashed line indicates cutoff for clustering;
(a) Example of isolated hotspot event without uniform dendritic activation; (b) Example of hotspot event before (black) and after (red) correction for uniform (putative bAP) dendritic contamination (dashed line); (c) Hotspot spatial size is not significantly different between events with small and large uniform dendritic activation; box boundaries indicate 25th and 75th percentiles, whiskers are minima and values adjacent to 1.5*IQR+75th percentiles
Summed spine, hotspot, and somatic tuning curves (dashed lines), spine-soma I/O functions (blue), and hotspot-soma I/O functions (red) for all imaged neurons, as in Supplementary Figure 5
About this article
Cite this article
Wilson, D., Whitney, D., Scholl, B. et al. Orientation selectivity and the functional clustering of synaptic inputs in primary visual cortex. Nat Neurosci 19, 1003–1009 (2016). https://doi.org/10.1038/nn.4323
Cell Calcium (2021)
Assessment of optogenetically-driven strategies for prosthetic restoration of cortical vision in large-scale neural simulation of V1
Scientific Reports (2021)
International Journal of Molecular Sciences (2021)
Seminars in Cell & Developmental Biology (2021)
Current Opinion in Neurobiology (2021)