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Multilaminar networks of cortical neurons integrate common inputs from sensory thalamus

Nature Neuroscience volume 19, pages 1034–1040 (2016)Cite this article

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Abstract

Neurons in the thalamorecipient layers of sensory cortices integrate thalamic and recurrent cortical input. Cortical neurons form fine-scale, functionally cotuned networks, but whether interconnected cortical neurons within a column process common thalamocortical inputs is unknown. We tested how local and thalamocortical connectivity relate to each other by analyzing cofluctuations of evoked responses in cortical neurons after photostimulation of thalamocortical axons. We found that connected pairs of pyramidal neurons in layer (L) 4 of mouse visual cortex share more inputs from the dorsal lateral geniculate nucleus than nonconnected pairs. Vertically aligned connected pairs of L4 and L2/3 neurons were also preferentially contacted by the same thalamocortical axons. Our results provide a circuit mechanism for the observed amplification of sensory responses by L4 circuits. They also show that sensory information is concurrently processed in L4 and L2/3 by columnar networks of interconnected neurons contacted by the same thalamocortical axons.

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Figure 1: dLGN→V1 inputs strongly innervate L4 and deep L2/3 pyramidal neurons.
Figure 2: Method for assessing how local and long-range connectivity relate to each other.
Figure 3: Simulations of how cofluctuations depend on the number of recruited inputs and the fraction of shared axons.
Figure 4: Interconnected neurons in L4 receive common dLGN inputs.
Figure 5: dLGN axons preferentially innervate L4→L2/3 connected pairs.

Change history

  • 12 July 2016

    In the version of this article initially published online, the abstract referred to connected pairs of L4 and L2 and 3 (L2/3) neurons. It should have read L4 and L2/3 neurons. The error has been corrected for the print, PDF and HTML versions of this article.

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Acknowledgements

We thank G. Shepherd, S. Peron, B. Atallah, H. Young, M. Fridman, A. Renart, S. Druckmann, T. Marques and C. Machens for comments on the manuscript. This work was supported by fellowships from Fundação para a Ciência e a Tecnologia to N.A.M. and J.B., a Marie Curie (PCIG12-GA-2012-334353) grant and a Human Frontier Science Program grant to L.P. and by the Champalimaud Foundation.

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Authors and Affiliations

  1. Champalimaud Neuroscience Programme, Champalimaud Center for the Unknown, Lisbon, Portugal

    Nicolás A Morgenstern, Jacques Bourg & Leopoldo Petreanu

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  1. Nicolás A Morgenstern
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  2. Jacques Bourg
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  3. Leopoldo Petreanu
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Contributions

N.A.M. and L.P. designed the study. L.P. built the experimental setup. N.A.M. performed the experiments. J.B. developed the model. N.A.M. and L.P. analyzed the data. N.A.M and L.P. wrote the manuscript with input from J.B.

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Correspondence to Leopoldo Petreanu.

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The authors declare no competing financial interests.

Integrated supplementary information

Supplementary Figure 1 dLGN inputs innervate L5 pyramidal neurons in V1.

Top. Average sCRACM maps aligned by pia position (white triangles, soma position). Bottom. Average sCRACM maps aligned by soma. Only neurons receiving significant dLGN inputs (3 out of 11 neurons) are plotted.

Supplementary Figure 2 Laminar, morphological and electrophysiological differences between L4 and L2/3 pyramidal neurons.

(a) Laminar position of paired recorded neurons in L4, L2/3 or L4 and L2/3. (b) Neuronal dendritic morphology reconstructions form L2/3 (top) or L4 (bottom) neurons. (c) Input/output curves from L2/3 or L4 neurons. (d) Intrinsic properties of L4 and L2/3 recorded neurons. Vm: P = 3.02 × 10−7, t-test (t172 = −5.33). Cm: P = 1.24 × 10−26, t-test (t132 = −13.5). Rm: P = 0.1312, t-test (t132 = 1.52). Vm: membrane resting potential. Cm: membrane capacitance. Rm: membrane resistance.

Supplementary Figure 3 Example experiments from connected and nonconnected pairs of neurons in V1.

(a,e,i,m) Local connectivity test. Presynaptic spiking elicited for each neuron (top) and the traces simultaneously recorded in the other neuron (bottom). Traces are the mean of 100 repetitions. (b,f,j,n) Brightfield image of the brain slice showing the recording pipettes and the photostimulation grid. (c,g,k,o) Maps of mean eEPSC charge (top) and response probability (bottom) across photostimulated locations in b,f,j,n respectively for each neuron in the pair. White triangles, soma position. (d,h,l,p) Top, map of mean number of inputs recruited for the pair at each photostimulated location in the grid (average of top panels in c,g,k,o respectively). Mean number of inputs is calculated as the mean eEPSC charge for the pair / TC unitary input size. White circles indicate locations with correlated eEPSCs. Bottom, fraction of correlated locations as function of mean number of inputs. Bin size, 1 input. Shaded area, range used for analyses in Fig. 4 and Fig. 5. Pixels with values within that range are marked with black dots in top panel.

Supplementary Figure 4 Photostimulation fails to evoke suprathreshold responses in V1 neurons.

(a) Example photostimulation experiment in current-clamp showing subthreshold membrane potential depolarizations evoked at each location for a pair of neurons (circles). (b) Summary table for depolarizations recorded in current-clamp from L2/3 and L4 neurons.

Supplementary Figure 5 The fraction of correlated locations increases with the number of recruited inputs.

(a) Fraction of locations with correlated inputs as a function of the mean number of inputs recruited from all photostimulated locations and all the pairs in L4, L2/3 or L4→L2/3 (connected and not connected pairs pooled together). Bin size 1 input. Exact fraction of correlated locations in each bin are shown for L4, L2/3 and L4→L2/3 pairs. First 4 bins are the same data as in Fig. 4 b, e and Fig. 5 d. (b) Mean number of inputs versus distance of the photostimulated locations to each L4 pair (center of both somata). Bin size, 100 μm. The number of locations in each bin is shown. (c) Fraction of correlated locations as function of distance to the pair for all L4 pairs. Bin size, 100 μm. The fraction of correlated locations in each bin is shown. The number of inputs recruited is larger in perisomatic areas resulting in a larger fraction of correlated locations close to the somata in L4 pairs.

Supplementary Figure 6 Connection strength is a weak predictor of shared input.

Relationship between the fraction of correlated locations and the connection strength for L4 (a), L2/3 (b) and L4→L2/3 (c) pairs. Gray line, linear regression fit.

Supplementary Figure 7 Intersomatic distances of the recorded pairs.

Lateral (a,b,c), vertical (d,e,f) and total distance (g,h,i) for the connected and not connected pairs in each group. L4→L2/3 distances are shown for all pairs (left) or only the pairs within 60 μm of lateral distance (right). P value for Wilcoxon rank sum test between groups is shown in each panel. Horizontal lines, mean. (j,k,l) Fraction of correlated locations as function of lateral distance for L4, L2/3 and L4→L2/3 pairs. Gray line, linear regression fit. Filled dots, bidirectionally connected pairs. For L4→L2/3 pairs there was a significant effect of horizontal distance on the fraction of correlated locations. However, as there was only one connected pair at distances > 60 μm, the effect could be due to connectivity and not distance. To disambiguate this we compared correlations only for pairs < 60 μm apart. While lateral displacement was very similar across the two groups (panel c, right), the fraction of correlated locations was still larger in the connected group (inset in panel l, fraction of correlated locations for individual vertical pairs within 60 μm of lateral distance; P < 0.02 Wilcoxon rank sum test).

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Morgenstern, N., Bourg, J. & Petreanu, L. Multilaminar networks of cortical neurons integrate common inputs from sensory thalamus. Nat Neurosci 19, 1034–1040 (2016). https://doi.org/10.1038/nn.4339

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