Nature | Vol 582 | 25 June 2020 | 545Article
Feedback generates a second receptive field
in neurons of the visual cortex
Andreas J. Keller1,2 ✉, Morgane M. Roth1,2 & Massimo Scanziani1,2 ✉Animals sense the environment through pathways that link sensory organs to the
brain. In the visual system, these feedforward pathways define the classical
feedforward receptive field (ffRF), the area in space in which visual stimuli excite a
neuron^1. The visual system also uses visual context—the visual scene surrounding a
stimulus—to predict the content of the stimulus^2 , and accordingly, neurons have been
identified that are excited by stimuli outside their ffRF^3 –^8. However, the mechanisms
that generate excitation to stimuli outside the ffRF are unclear. Here we show that
feedback projections onto excitatory neurons in the mouse primary visual cortex
generate a second receptive field that is driven by stimuli outside the ffRF. The
stimulation of this feedback receptive field (fbRF) elicits responses that are slower and
are delayed in comparison with those resulting from the stimulation of the ffRF. These
responses are preferentially reduced by anaesthesia and by silencing higher visual
areas. Feedback inputs from higher visual areas have scattered receptive fields
relative to their putative targets in the primary visual cortex, which enables the
generation of the fbRF. Neurons with fbRFs are located in cortical layers that receive
strong feedback projections and are absent in the main input layer, which is consistent
with a laminar processing hierarchy. The observation that large, uniform stimuli—
which cover both the fbRF and the ffRF—suppress these responses indicates that the
fbRF and the ffRF are mutually antagonistic. Whereas somatostatin-expressing
inhibitory neurons are driven by these large stimuli, inhibitory neurons that express
parvalbumin and vasoactive intestinal peptide have mutually antagonistic fbRF and
ffRF, similar to excitatory neurons. Feedback projections may therefore enable
neurons to use context to estimate information that is missing from the ffRF and to
report differences in stimulus features across visual space, regardless of whether
excitation occurs inside or outside the ffRF. By complementing the ffRF, the fbRF that
we identify here could contribute to predictive processing.To characterize the ffRF, we mapped receptive field locations of layer
2/3 (L2/3) excitatory neurons in primary visual cortex (V1) of awake,
head-fixed mice using two-photon calcium imaging (Fig. 1a). The centre
of the ffRF of a given neuron was determined using circular patches of
drifting gratings presented individually at different locations (Fig. 1b).
To estimate the size of the ffRF, we obtained a size-tuning function
by varying the diameter of the grating (Fig. 1c) centred on the ffRF of
the neuron (Methods). The responses were maximal for gratings of
13.1 ± 0.4° in diameter and were suppressed with increasing grating
size (Fig. 1c), consistent with previous reports^9 –^12.
To determine the spatial extent of the suppressive regions, we pre-
sented a full-field grating in which a portion was masked by a circular
grey patch (Fig. 1a, b). We reasoned that the response of the neuron
would partially recover upon placing the grey patch on a suppressive
region—that is, when part of the suppressive region is not stimulated.
We varied the location of the grey patch along the same grid that was
used to determine the location of the ffRF. We obtained two sepa-
rate population-averaged activity maps—the ffRF map and the map
for the suppressive regions—and found that the peak of these two
maps overlapped (Fig. 1b). Thus, the largest recovery from suppres-
sion occurred when the grey patch was located at the centre of the
ffRF.
To obtain a finer measure of the response of a neuron to a grey patch,
we placed the patch on the centre of the ffRF and varied its diameter.
Even the smallest size we tested (5°) evoked a response that was larger
than that to the full-field grating. Notably, neuronal responses first
increased and then decreased with increasing size of the grey patch
(Fig. 1c). These responses were not due to the sharp edges of the stimuli,
because similar responses were observed when the edges were blurred
(Extended Data Fig. 1). Thus, the size-tuning function of a grey patch
on a full-field grating (inverse stimulus) was similar to that of a grating
patch on a grey background (classical stimulus).https://doi.org/10.1038/s41586-020-2319-4
Received: 21 June 2019
Accepted: 10 March 2020
Published online: 20 May 2020
Check for updates(^1) Department of Physiology, University of California San Francisco, San Francisco, CA, USA. (^2) Howard Hughes Medical Institute, University of California San Francisco, San Francisco, CA, USA.
✉e-mail: [email protected]; [email protected]