Inhibition dominates sensory responses in the awake cortex

Journal name:
Nature
Volume:
493,
Pages:
97–100
Date published:
DOI:
doi:10.1038/nature11665
Received
Accepted
Published online

The activity of the cerebral cortex is thought to depend on the precise relationship between synaptic excitation and inhibition1, 2, 3, 4. In the visual cortex, in particular, intracellular measurements have related response selectivity to coordinated increases in excitation and inhibition5, 6, 7, 8, 9. These measurements, however, have all been made during anaesthesia, which strongly influences cortical state10 and therefore sensory processing7, 11, 12, 13, 14, 15. The synaptic activity that is evoked by visual stimulation during wakefulness is unknown. Here we measured visually evoked responses—and the underlying synaptic conductances—in the visual cortex of anaesthetized and awake mice. Under anaesthesia, responses could be elicited from a large region of visual space16 and were prolonged. During wakefulness, responses were more spatially selective and much briefer. Whole-cell patch-clamp recordings of synaptic conductances5, 17 showed a difference in synaptic inhibition between the two conditions. Under anaesthesia, inhibition tracked excitation in amplitude and spatial selectivity. By contrast, during wakefulness, inhibition was much stronger than excitation and had extremely broad spatial selectivity. We conclude that during wakefulness, cortical responses to visual stimulation are dominated by synaptic inhibition, restricting the spatial spread and temporal persistence of neural activity. These results provide a direct glimpse of synaptic mechanisms that control sensory responses in the awake cortex.

At a glance

Figures

  1. Spontaneous and evoked activity in the anaesthetized and awake visual cortex (V1).
    Figure 1: Spontaneous and evoked activity in the anaesthetized and awake visual cortex (V1).

    a, Vm and simultaneous LFP measured in V1 under anaesthesia. The spikes are shown truncated at +20mV. b, Vm and simultaneous LFP measured in V1 in awake animals. c, d, Visually evoked LFP responses across space during anaesthesia (c) and wakefulness (d). An average of 15 trials per location was used. Top, the dashed line indicates the best location. Bottom, single trial responses (grey) and the average (mean±s.e.m.) response (black or green) with the stimulus (stim) at the best location. deg, degrees. e, Vm responses to stimuli at the best location while under anaesthesia: single trials (grey) and mean (±s.e.m.; black). The spikes are shown truncated at −30mV. f, Vm responses to stimuli at the best location during wakefulness. cf, n = 4 different mice. g, h, Normalized probability distributions of Vm response durations to stimuli at the best location, across the population (n = 14), measured under anaesthesia (g) and during wakefulness (h). The arrow indicates the mean duration.

  2. Anaesthetized responses are long lasting regardless of cortical state.
    Figure 2: Anaesthetized responses are long lasting regardless of cortical state.

    a, b, Normalized probability distributions of spontaneous Vm during anaesthesia (n = 14 neurons) (a) and wakefulness (n = 14 neurons) (b). c, Mean (±s.e.m.) anaesthetized Vm responses (solid lines), sorted by pre-stimulus Vm level. Depolarized (grey) and hyperpolarized (black) groups are shown (with the mean Vm of the two groups indicated by arrows of the corresponding colour in a). The pre-stimulus baseline Vm was subtracted before averaging. The dashed lines indicate the average spontaneous Vm (in response to blank stimuli), sorted similarly into two groups (n = 14 neurons). d, As for c, during wakefulness (n = 14). e, Average anaesthetized Vm response for hyperpolarized (black) and depolarized (grey) trials, after subtraction of spontaneous Vm traces. f, Average awake Vm response for all trials, after subtraction of spontaneous Vm traces. The grey line shows the average of all of the anaesthetized responses (for comparison).

  3. Responses are spatiotemporally restricted during waking.
    Figure 3: Responses are spatiotemporally restricted during waking.

    a, The number of spikes evoked per trial (normalized to each neuron’s response at the best location). Symmetrical locations on either side of 0° were combined. The centre is defined as 0°±9°, and the surround is defined as ±18° to ±45°. The response window is defined by the average duration of the population’s Vm response (Fig. 1g, h) (n = 14 for each group). b, Under anaesthesia (anaesth, black), centre and surround stimuli evoked more spikes (P<0.001 for both) than during spontaneous activity (dashed line). During wakefulness (green), there were fewer spikes than under anaesthesia (P<0.001 for both stimulus locations); the centre stimuli evoked more spikes than did the surround stimuli (P<0.009), and the surround stimuli did not evoke a significantly different response from spontaneous activity. Nine of 14 neurons were active during anaesthesia, and 5 of 14 were active during waking. c, As for a, for peak Vm responses (normalized to each neuron’s response at the best location). d, As for b, for peak Vm responses. The responses to centre stimuli were greater than to surround stimuli in both anaesthetized and awake animals (P<0.04 for both conditions), and all responses were greater than spontaneous activity (dashed lines, P<0.001 for all). The awake responses were larger than the anaesthetized responses (P<0.001 for both stimuli locations). e, The Vm and the spike responses were more spatially selective during waking (Vm, anaesthetized, 0.3±0.1; awake, 0.6±0.1; P<0.001; and spikes, anaesthetized, 0.1±0.1; awake, 0.6±0.2; P<0.001). f, The spike-triggered average of Vm under anaesthesia and during wakefulness. The spike threshold (the peak of the second derivative of Vm) was aligned at 0mV. af, mean±s.e.m.

  4. Visually evoked conductance is dominated by inhibition in awake V1.
    Figure 4: Visually evoked conductance is dominated by inhibition in awake V1.

    a, b, ΔGe (red) and ΔGi (blue) evoked by centre stimulation during anaesthesia (n = 5) and waking (n = 8). c, ΔGe and ΔGi evoked by surround stimulation during anaesthesia (c) and waking (d) (for the same neurons as in a and b). e, Spatial profiles of excitation and inhibition under anaesthesia (left) and wakefulness (right). ΔGe and ΔGi were normalized to peak ΔGe for centre stimuli (grey dashed line) for each neuron and then averaged across the population. Data were fitted with a Gaussian function (mean±s.d., shaded) or a linear function (for the awake Gi; mean±s.d.). Scale bar, 18° width across the receptive field centre. ad, mean±s.e.m.

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Affiliations

  1. UCL Institute of Ophthalmology, University College London, 11–43 Bath Street, London EC1V 9EL, UK

    • Bilal Haider &
    • Matteo Carandini
  2. Wolfson Institute for Biomedical Research and Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, UK

    • Michael Häusser

Contributions

B.H. performed the experiments. B.H. and M.C. performed the analyses. B.H., M.H. and M.C. designed the study and wrote the paper.

Competing financial interests

The authors declare no competing financial interests.

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  1. Supplementary Figures (3.1 MB)

    This file contains Supplementary Figures 1-11. Supplementary Figure 8 was corrected on 10 July 2013; see corrigendum linked to original manuscript for details.

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