Abstract
Of all of the sensory areas, barrel cortex is among the best understood in terms of circuitry, yet least understood in terms of sensory function. We combined intracellular recording in rats with a multi-directional, multi-whisker stimulator system to estimate receptive fields by reverse correlation of stimuli to synaptic inputs. Spatiotemporal receptive fields were identified orders of magnitude faster than by conventional spike-based approaches, even for neurons with little spiking activity. Given a suitable stimulus representation, a linear model captured the stimulus-response relationship for all neurons with high accuracy. In contrast with conventional single-whisker stimuli, complex stimuli revealed markedly sharpened receptive fields, largely as a result of adaptation. This phenomenon allowed the surround to facilitate rather than to suppress responses to the principal whisker. Optimized stimuli enhanced firing in layers 4–6, but not in layers 2/3, which remained sparsely active. Surround facilitation through adaptation may be required for discriminating complex shapes and textures during natural sensing.
This is a preview of subscription content, access via your institution
Relevant articles
Open Access articles citing this article.
-
Learning enhances encoding of time and temporal surprise in mouse primary sensory cortex
Nature Communications Open Access 20 September 2022
-
Reverse-Correlation Analysis of the Mechanosensation Circuit and Behavior in C. elegans Reveals Temporal and Spatial Encoding
Scientific Reports Open Access 26 March 2019
-
A radial map of multi-whisker correlation selectivity in the rat barrel cortex
Nature Communications Open Access 21 November 2016
Access options
Subscribe to this journal
Receive 12 print issues and online access
$189.00 per year
only $15.75 per issue
Rent or buy this article
Get just this article for as long as you need it
$39.95
Prices may be subject to local taxes which are calculated during checkout








References
Brecht, M., Roth, A. & Sakmann, B. Dynamic receptive fields of reconstructed pyramidal cells in layers 3 and 2 of rat somatosensory barrel cortex. J. Physiol. (Lond.) 553, 243–265 (2003).
Manns, I.D., Sakmann, B. & Brecht, M. Sub- and suprathreshold receptive field properties of pyramidal neurones in layers 5A and 5B of rat somatosensory barrel cortex. J. Physiol. (Lond.) 556, 601–622 (2004).
Moore, C.I. & Nelson, S.B. Spatio-temporal subthreshold receptive fields in the vibrissa representation of rat primary somatosensory cortex. J. Neurophysiol. 80, 2882–2892 (1998).
Zhu, J.J. & Connors, B.W. Intrinsic firing patterns and whisker-evoked synaptic responses of neurons in the rat barrel cortex. J. Neurophysiol. 81, 1171–1183 (1999).
de Kock, C.P., Bruno, R.M., Spors, H. & Sakmann, B. Layer- and cell type–specific suprathreshold stimulus representation in rat primary somatosensory cortex. J. Physiol. (Lond.) 581, 139–154 (2007).
Hemelt, M.E., Kwegyir-Afful, E.E., Bruno, R.M., Simons, D.J. & Keller, A. Consistency of angular tuning in the rat vibrissa system. J. Neurophysiol. 104, 3105–3112 (2010).
Ritt, J.T., Andermann, M.L. & Moore, C.I. Embodied information processing: vibrissa mechanics and texture features shape micromotions in actively sensing rats. Neuron 57, 599–613 (2008).
Carvell, G.E. & Simons, D.J. Biometric analyses of vibrissal tactile discrimination in the rat. J. Neurosci. 10, 2638–2648 (1990).
Diamond, M.E., von Heimendahl, M., Knutsen, P.M., Kleinfeld, D. & Ahissar, E. 'Where' and 'what' in the whisker sensorimotor system. Nat. Rev. Neurosci. 9, 601–612 (2008).
Bruno, R.M., Hahn, T.T., Wallace, D.J., de Kock, C.P. & Sakmann, B. Sensory experience alters specific branches of individual corticocortical axons during development. J. Neurosci. 29, 3172–3181 (2009).
Simons, D.J. Temporal and spatial integration in the rat SI vibrissa cortex. J. Neurophysiol. 54, 615–635 (1985).
Brumberg, J.C., Pinto, D.J. & Simons, D.J. Spatial gradients and inhibitory summation in the rat whisker barrel system. J. Neurophysiol. 76, 130–140 (1996).
Drew, P.J. & Feldman, D.E. Representation of moving wavefronts of whisker deflection in rat somatosensory cortex. J. Neurophysiol. 98, 1566–1580 (2007).
Hirata, A. & Castro-Alamancos, M.A. Cortical transformation of wide-field (multiwhisker) sensory responses. J. Neurophysiol. 100, 358–370 (2008).
Higley, M.J. & Contreras, D. Integration of synaptic responses to neighboring whiskers in rat barrel cortex in vivo. J. Neurophysiol. 93, 1920–1934 (2005).
Shimegi, S., Ichikawa, T., Akasaki, T. & Sato, H. Temporal characteristics of response integration evoked by multiple whisker stimulations in the barrel cortex of rats. J. Neurosci. 19, 10164–10175 (1999).
Ego-Stengel, V., Mello e Souza, T., Jacob, V. & Shulz, D.E. Spatiotemporal characteristics of neuronal sensory integration in the barrel cortex of the rat. J. Neurophysiol. 93, 1450–1467 (2005).
Jacob, V., Le Cam, J., Ego-Stengel, V. & Shulz, D.E. Emergent properties of tactile scenes selectively activate barrel cortex neurons. Neuron 60, 1112–1125 (2008).
Sharpee, T.O. Computational identification of receptive fields. Annu. Rev. Neurosci. 36, 103–120 (2013).
Barth, A.L. & Poulet, J.F. Experimental evidence for sparse firing in the neocortex. Trends Neurosci. 35, 345–355 (2012).
Constantinople, C.M. & Bruno, R.M. Effects and mechanisms of wakefulness on local cortical networks. Neuron 69, 1061–1068 (2011).
O'Connor, D.H., Peron, S.P., Huber, D. & Svoboda, K. Neural activity in barrel cortex underlying vibrissa-based object localization in mice. Neuron 67, 1048–1061 (2010).
Estebanez, L., El Boustani, S., Destexhe, A. & Shulz, D.E. Correlated input reveals coexisting coding schemes in a sensory cortex. Nat. Neurosci. 15, 1691–1699 (2012).
Ahrens, M.B., Paninski, L. & Sahani, M. Inferring input nonlinearities in neural encoding models. Network 19, 35–67 (2008).
Ebara, S., Kumamoto, K., Matsuura, T., Mazurkiewicz, J.E. & Rice, F.L. Similarities and differences in the innervation of mystacial vibrissal follicle-sinus complexes in the rat and cat: a confocal microscopic study. J. Comp. Neurol. 449, 103–119 (2002).
Priebe, N.J. & Ferster, D. Inhibition, spike threshold and stimulus selectivity in primary visual cortex. Neuron 57, 482–497 (2008).
Martinez, L.M. et al. Receptive field structure varies with layer in the primary visual cortex. Nat. Neurosci. 8, 372–379 (2005).
Atencio, C.A., Sharpee, T.O. & Schreiner, C.E. Cooperative nonlinearities in auditory cortical neurons. Neuron 58, 956–966 (2008).
Sahani, M. & Linden, J.F. How linear are auditory cortical responses? Adv. Neural Inf. Process. Syst. 15, 277–284 (2003).
Mirabella, G., Battiston, S. & Diamond, M.E. Integration of multiple-whisker inputs in rat somatosensory cortex. Cereb. Cortex 11, 164–170 (2001).
Simons, D.J. & Carvell, G.E. Thalamocortical response transformation in the rat vibrissa/barrel system. J. Neurophysiol. 61, 311–330 (1989).
Higley, M.J. & Contreras, D. Nonlinear integration of sensory responses in the rat barrel cortex: an intracellular study in vivo. J. Neurosci. 23, 10190–10200 (2003).
Boloori, A.R. & Stanley, G.B. The dynamics of spatiotemporal response integration in the somatosensory cortex of the vibrissa system. J. Neurosci. 26, 3767–3782 (2006).
Boloori, A.R., Jenks, R.A., Desbordes, G. & Stanley, G.B. Encoding and decoding cortical representations of tactile features in the vibrissa system. J. Neurosci. 30, 9990–10005 (2010).
Minnery, B.S. & Simons, D.J. Response properties of whisker-associated trigeminothalamic neurons in rat nucleus principalis. J. Neurophysiol. 89, 40–56 (2003).
Bruno, R.M., Khatri, V., Land, P.W. & Simons, D.J. Thalamocortical angular tuning domains within individual barrels of rat somatosensory cortex. J. Neurosci. 23, 9565–9574 (2003).
Bruno, R.M. & Sakmann, B. Cortex is driven by weak but synchronously active thalamocortical synapses. Science 312, 1622–1627 (2006).
Longordo, F., To, M.S., Ikeda, K. & Stuart, G.J. Sublinear integration underlies binocular processing in primary visual cortex. Nat. Neurosci. 16, 714–723 (2013).
Varga, Z., Jia, H., Sakmann, B. & Konnerth, A. Dendritic coding of multiple sensory inputs in single cortical neurons in vivo. Proc. Natl. Acad. Sci. USA 108, 15420–15425 (2011).
Machens, C.K., Wehr, M.S. & Zador, A.M. Linearity of cortical receptive fields measured with natural sounds. J. Neurosci. 24, 1089–1100 (2004).
Jadhav, S.P., Wolfe, J. & Feldman, D.E. Sparse temporal coding of elementary tactile features during active whisker sensation. Nat. Neurosci. 12, 792–800 (2009).
Smyth, D., Willmore, B., Baker, G.E., Thompson, I.D. & Tolhurst, D.J. The receptive-field organization of simple cells in primary visual cortex of ferrets under natural scene stimulation. J. Neurosci. 23, 4746–4759 (2003).
Constantinople, C.M. & Bruno, R.M. Deep cortical layers are activated directly by thalamus. Science 340, 1591–1594 (2013).
Polack, P.O., Friedman, J. & Golshani, P. Cellular mechanisms of brain state–dependent gain modulation in visual cortex. Nat. Neurosci. 16, 1331–1339 (2013).
Higley, M.J. & Contreras, D. Cellular mechanisms of suppressive interactions between somatosensory responses in vivo. J. Neurophysiol. 97, 647–658 (2007).
Katz, Y., Heiss, J.E. & Lampl, I. Cross-whisker adaptation of neurons in the rat barrel cortex. J. Neurosci. 26, 13363–13372 (2006).
Chung, S., Li, X. & Nelson, S.B. Short-term depression at thalamocortical synapses contributes to rapid adaptation of cortical sensory responses in vivo. Neuron 34, 437–446 (2002).
Fournier, J., Monier, C., Pananceau, M. & Fregnac, Y. Adaptation of the simple or complex nature of V1 receptive fields to visual statistics. Nat. Neurosci. 14, 1053–1060 (2011).
Fanselow, E.E. & Nicolelis, M.A. Behavioral modulation of tactile responses in the rat somatosensory system. J. Neurosci. 19, 7603–7616 (1999).
Wang, Q., Webber, R.M. & Stanley, G.B. Thalamic synchrony and the adaptive gating of information flow to cortex. Nat. Neurosci. 13, 1534–1541 (2010).
Geffen, M.N., Broome, B.M., Laurent, G. & Meister, M. Neural encoding of rapidly fluctuating odors. Neuron 61, 570–586 (2009).
Recht, B., Fazel, M. & Parrilo, P.A. Guaranteed minimum-rank solutions of linear matrix equations via nuclear norm minimization. SIAM Rev. 52, 471–501 (2010).
Boyd, S., Parikh, N., Chu, E., Peleato, B. & Eckstein, J. Distributed optimization and statistical learning via the alternating direction method of multipliers. Found. Trends Mach. Learn. 3, 1–122 (2011).
Acknowledgements
We thank S. Fusi, M. Rigotti, K. Hong, E. Zhang and C. Rodgers for comments on the manuscript, D. Baughman for technical support, and D. Pfau for participating in pilot experiments. This project was supported by grants from the National Institute of Neurological Disorders and Stroke (RO1 NS069679 to R.M.B., F31 NS076338-01 to A.R., and R01-EY11001 to K.D.M.), the Rita Allen Foundation (R.M.B.), the Grossman Center for Statistics of Mind (R.M.B.), the Gatsby Charitable Foundation through the Gatsby Initiative in Brain Circuitry at Columbia University (K.D.M.), and a National Science Foundation CAREER award (L.P.).
Author information
Authors and Affiliations
Contributions
R.M.B. conceived the study. A.R. and R.M.B. designed the experiments. A.R. performed the experiments. A.R., E.A.P., J.M., K.D.M., L.P. and R.M.B. designed the analyses. A.R. performed the analyses. A.R. and R.M.B. wrote the manuscript.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Integrated supplementary information
Supplementary Figure 1 Pulse waveform, stimulus representation, and example STA and STA'.
a, An example of the waveform of individual pulse deflections (left) with the actual movement of the stimulator overlaid in green. The X,Y representation of movement for a single whisker for 1 second of complex stimuli (right). Below is a schematic of the binary representation of whisker movements for the same whisker in the 8-dimensional stimulus representation. Each whisker's state was represented in a given 1-ms time bin, where a 1 indicates the onset of a deflection in one of eight 45° bins. b, The VWA (left) for three example neurons is used to predict the STA' and compared to the actual STA (middle, and correlation coefficient). The model is also used to predict the STA' for 30000 extra trials of stimuli (right). For some neurons with low firing rates the STA-STA' correlation is low (top) and for some neurons with high firing rates the STA can be noisy (bottom). Nonetheless, for all neurons the VWA can be used to predict the STA' and has high correlation to the true STA (Fig. 1d,e).
Supplementary Figure 2 Fraction of predictable variance accounted for by our model.
Unbiased estimators of noise-related variance in our neural responses and the fraction of predictable variance accounted for by our model were calculated as in Sahani & Linden 2003. Black, training data. Gray, testing data. Extrapolating the performance of the model to conditions of zero noise gave an upper-bound of predictable variance of 0.75 ± 0.06 and a lower bound of 0.58 ± 0.03. b, The relationship between neural variability and firing rate. The firing rate is plotted by neuron and depth alongside a similar plot for variability by neuron and depth. c, There is no significant relationship between the firing rate and neural variability (right, p-value = 0.22). d, The firing rate (left) and signal-to-noise ratio, SNR (right), calculated as in Sahani & Linden 2003, are plotted by cell type. Neurons with high firing rates can have both low SNR (L5TT) or high SNR (L4) and neurons with low firing rates can have both low SNR (L2) as well as high SNR (L3 and L6).
Supplementary Figure 3 Shifting the angle bins does not impair model performance.
The 8-dimensional representation binned in cardinal directions (top left) was compared against one where the bins were shifted by 22.5° (top right). For each neuron, model performance using the cardinal stimulus representation was plotted against performance using the shifted representation (bottom). The least-squares regression of the data (red) falls exactly over the unity line (blue) demonstrating that cardinal directions play no special role and that this level of directional discretization (45° wide bins) used in our is adequate.
Supplementary Figure 4 Linearity is not dependent on stimulus frequency.
A linear model was fit using our standard 10 Hz stimuli and then cross validated on 10, 30 and 60 Hz stimuli. a, an example neuron. For each plot on the left the gray traces illustrate ten trials of frozen noise, along with the average response (blue) and predicted response (red). On the right, the voltage predicted by our model is plotted against the actual voltage of the neuron for each 1-ms time bin (gray). Blue dots are the binned meaned data. The red line is the least-squares regression of the data, which can be compared to the unity line (gray). Although model performance (R2) dropped as the frequency of stimulus increased from 10 to 30 to 60 Hz, the apparent linearity in fact increased (red line closer to unity, indicated by brackets). b, The R2 for the model tested at 10, 30, and 60 Hz stimuli (N = 30 cells; not all three conditions were available for all neurons). There was a consistent drop in performance for almost all neurons as the frequency of whisker stimuli increased. However, c, the normalized signal-to-noise ratio (SNR) at 10, 30, and/or 60 Hz, as calculated in Sahani and Linden 2003, for the vast majority of cells dropped (both increased noise and decreased signal) as the frequency increases, explaining the drop in model performance seen in b. The neurons where the SNR increased in panel c were the same neurons where model performance also increased in panel b. d, To verify that the model was linearly dependent on the variability of the neuron and independent of stimulus frequency, we plotted the performance of the model against the trial-to-trial variability of the neurons (as in Fig. 2c). There was a similar relationship irrespective of whether models were tested on 10, 30, or 60 Hz stimuli. e. For a subset of neurons (N=5) we trained and tested the linear (black) and quadratic (gray) models at both 10 Hz and 30 Hz stimuli and compared the R2 values. The linear model consistently outperformed the quadratic model, even at higher stimulus frequencies. The average of the linear model is shown in red and the average of the quadratic model is shown in cyan.
Supplementary Figure 5 Four temporal basis components are sufficient to describe the receptive fields of all neurons in the population.
To find shared temporal basis components across neurons, we can simply stack the VWAs of all of the neurons together (to form a 100 by (72*N) matrix where N=number of neurons) and run singular value decomposition on this large matrix. The first few temporal components will be selected to allow for optimal squared error reconstruction of all of the VWAs. From left to right, the plots depict the predictive performance of various reduced rank models (reconstructed from 1 to 4 shared temporal basis components) against full rank models (100 temporal basis components). The rank refers to the rank of the RF matrices with temporal basis components shared across neurons. Critically, the temporal basis components are the same for all neurons, so the low number of components required to match full rank performance demonstrates that there is shared structure in the temporal components of the VWAs across all neurons. By rank 3, the low rank model predictive performance is approximately equivalent to the full rank model, demonstrating no more than 3 or 4 temporal basis components are required to capture the RFs of any neuron in the population.
Supplementary Figure 6 Topological representation of STRFs.
a, The average STRFs from Fig. 5a are represented in a manner that maintains the topological organization of the whiskers. The inset shows the polar plot of responses for each respective whisker. b, The fraction of power contained by each of the whiskers in the receptive field is plotted in order to show the spatial gradient of responses. c, The latency of surround whisker responses relative to the PW response are plotted according to whisker location and the average for all is plotted to the right to show the optimal inter-whisker latencies by layer and cell type.
Supplementary Figure 7 Surrounds lack strong subthreshold spatial gradients but tend to have similar directional tuning to the principal whisker.
a, For all neurons in either the adapted state (N = 71) or the unadapted state (N = 68), the dorso-ventral and caudal-rostral response gradients in the receptive fields were calculated as in previous studies (see Brumberg, Pinto & Simons 1996, Bruno & Simons 2002; i.e., (Responsedorsal – Responseventral) / (Responsedorsal + Responseventral) ) and a histogram of responses was plotted for the dorso-ventral bias (left) and caudal-rostral bias (right). b, Spatial gradients of latency of the surround response were similarly calculated. c, The relationship of the PW and SW tuning was calculated, for each neuron, as the mean correlation of the PW and each significantly responding surround whisker. A value of 1 would indicate that the directional tuning of all significant SWs were identical to the directional tuning of the PW; -1 that the directional tuning of all significant SWs were opposite to that of the PW. Note that, while SWs tend to be tuned like the PW, many cells are oppositely tuned or uncorrelated.
Supplementary Figure 8 Facilitation of adapted responses is independent of the precise nature of background stimuli.
a, The facilitation index (the magnitude of the optimal multi-whisker response divided by the PW response, Opt PSP/PW PSP) does not depend on the proximity of the preceding background stimulus (p = 0.42). Each data point represents a single trial observation of the optimal stimulus. b, The facilitation index does not depend on the number of simultaneously active background inputs (p = 0.29).
Supplementary information
Supplementary Text and Figures
Supplementary Figures 1–8 (PDF 947 kb)
Rights and permissions
About this article
Cite this article
Ramirez, A., Pnevmatikakis, E., Merel, J. et al. Spatiotemporal receptive fields of barrel cortex revealed by reverse correlation of synaptic input. Nat Neurosci 17, 866–875 (2014). https://doi.org/10.1038/nn.3720
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/nn.3720
This article is cited by
-
Learning enhances encoding of time and temporal surprise in mouse primary sensory cortex
Nature Communications (2022)
-
Reverse-Correlation Analysis of the Mechanosensation Circuit and Behavior in C. elegans Reveals Temporal and Spatial Encoding
Scientific Reports (2019)
-
Elementary motion sequence detectors in whisker somatosensory cortex
Nature Neuroscience (2019)
-
A radial map of multi-whisker correlation selectivity in the rat barrel cortex
Nature Communications (2016)
-
Sensory and decision-related activity propagate in a cortical feedback loop during touch perception
Nature Neuroscience (2016)