Visual experience and subsequent sleep induce sequential plastic changes in putative inhibitory and excitatory cortical neurons

Abstract

Ocular dominance plasticity in the developing primary visual cortex is initiated by monocular deprivation (MD) and consolidated during subsequent sleep. To clarify how visual experience and sleep affect neuronal activity and plasticity, we continuously recorded extragranular visual cortex fast-spiking (FS) interneurons and putative principal (i.e., excitatory) neurons in freely behaving cats across periods of waking MD and post-MD sleep. Consistent with previous reports in mice, MD induces two related changes in FS interneurons: a response shift in favor of the closed eye and depression of firing. Spike-timing-dependent depression of open-eye-biased principal neuron inputs to FS interneurons may mediate these effects. During post-MD nonrapid eye movement sleep, principal neuron firing increases and becomes more phase-locked to slow wave and spindle oscillations. Ocular dominance (OD) shifts in favor of open-eye stimulation--evident only after post-MD sleep--are proportional to MD-induced changes in FS interneuron activity and to subsequent sleep-associated changes in principal neuron activity. OD shifts are greatest in principal neurons that fire 40-300 ms after neighboring FS interneurons during post-MD slow waves. Based on these data, we propose that MD-induced changes in FS interneurons play an instructive role in ocular dominance plasticity, causing disinhibition among open-eye-biased principal neurons, which drive plasticity throughout the visual cortex during subsequent sleep.

Fig. 1.

Effects of visual experience and subsequent sleep on neuronal responses in freely behaving cats. (A) At the intervals indicated, visual responses to stimulation of the right and left eyes were compared, and ocular dominance indices (ODIs) were calculated for each neuron. An ODI of 0 indicates equal responsiveness to stimulation of either eye; ODIs of 1 and −1 indicate responsiveness to only left- or right-eye stimulation, respectively. FS interneurons showed an initial shift in favor of the closed eye after waking MD (P < 0.05 vs. baseline, repeated measures ANOVA), followed by a return to binocularity after subsequent sleep. Principal neurons were unchanged after waking MD, but shifted in favor of the open eye after subsequent sleep. (B) Open-eye responses (red) in FS interneurons were significantly depressed, and closed-eye responses (blue) were slightly enhanced, after MD; these changes were reversed, and open-eye and closed-eye responses returned to baseline levels after subsequent sleep. Open-eye and closed-eye responses in principal neurons were unchanged after waking MD alone, but were potentiated and depressed, respectively, after post-MD sleep (arrows indicate P < 0.05 vs. baseline, repeated measures ANOVA). (C) Closed-eye response changes in FS interneurons during MD correlated with subsequent plasticity in neighboring principal neurons during post-MD sleep. Values are averaged across all FS and principal neurons recorded on each stereotrode bundle (n = 8 recording sites at which both FS and principal neurons were recorded).

Fig. 2.

MD-induced depression of open-eye responses in FS interneurons is consistent with spike-timing–dependent plasticity. (A) Hypothesized changes in input to FS interneurons during MD are illustrated using a simplified circuit diagram, which takes into account the columnar organization of OD preference. Principal neurons and FS interneurons are shown as triangles and circles, and excitatory and inhibitory synaptic inputs are shown as arrowheads and balls, respectively. Depression of open-eye responses could be elicited by reduction in excitatory inputs from open-eye–biased principal neurons to FS interneurons. (B) A group of neurons recorded at the same site (three principal neurons and a neighboring FS interneuron), with each neuron’s baseline ODI. Cross-correlated firing was calculated between the FS interneuron and each principal neuron during baseline waking and in the first hour of MD. A similar analysis was carried out for each recorded FS interneuron. (C) In pairs of neurons where, initially, the principal neuron was more biased toward the open eye than the FS interneuron, cross-correlated firing within a ±10-ms lag increased the most during MD (calculated as a z-score change from baseline). Such an increase would be predicted to cause spike-timing–dependent depression of principal inputs to FS interneurons (19).

Fig. 3.

MD causes overall depression of firing in FS interneurons, which correlates with plasticity during post-MD sleep. (A) Mean firing for FS interneurons tended to decrease over the course of MD (relative to No-MD control conditions, filled and open circles, respectively). FS interneuron firing was significantly depressed in all states throughout the post-MD period relative to baseline levels (arrows indicate significant decrease following MD, Holm–Sidak post hoc test), but was transiently enhanced during sleep under No-MD conditions (main effects of visual experience, time, NS; visual experience × time interaction, F = 7.4; P < 0.001 for NREM; F = 6.9; P < 0.001 for REM, two-way repeated-measures ANOVA). Data represent mean ± SEM firing rate (in Hz) at each time point throughout recordings. (B) FS interneurons biased in favor of the open eye at baseline showed the most profound depression of firing during the first hours of post-MD REM and NREM sleep. (C) Spontaneous firing was similarly depressed in FS interneurons during OD testing after MD (relative to No-MD conditions; visual experience × time interaction, F = 6.5, P < 0.005; an asterisk indicates P < 0.05 between MD and No MD, Holm–Sidak test). (D) ODI changes in principal neurons during post-MD sleep (averaged across all neurons recorded in each cat) negatively correlated with spontaneous firing-rate changes in neighboring FS interneurons. (E) ODIs for principal neurons acutely recorded from anesthetized cats [after 1–2 h of post-MD sleep during the predicted nadir of FS interneuron firing (Fig. 3A and Fig. S4)] negatively correlated with spontaneous firing rates in neighboring FS interneurons (data averaged across all neurons at a given cortical site).

Fig. 4.

Principal neurons show increased firing during post-MD sleep. (A) Principal neuron activity was comparable during waking experience with or without MD, but increased significantly during post-MD NREM sleep (main effect of visual experience, F = 4.2, P < 0.05; main effect of time, visual experience × time interaction, NS, two-way repeated-measures ANOVA; arrow indicates significant increase vs. No-MD condition, Holm–Sidak post hoc test). Data represent mean ± SEM firing rate (in Hz) at each time point throughout recordings. (B) In principal neurons recorded after MD, firing-rate increases (from baseline) during post-MD NREM sleep correlated with ODI changes and with increases in open-eye response magnitude across the post-MD period. Firing-rate changes in REM sleep also correlated with open-eye response changes.

Fig. 5.

Changes in principal and FS neuron activity during post-MD NREM oscillations are proportional to plasticity. Post-MD changes in spike field coherence (during both slow wave and spindle oscillations) were proportional both to ODI changes (A) and to open-eye response potentiation (B) in principal neurons. (C) Distributions of mean firing phases relative to local slow wave and spindle oscillations are shown for neurons recorded from all cats at baseline and in the post-MD period. Each point represents one FS or principal neuron with mean spike phase at a given angle. Mean phase angle (θ) and r values for each distribution are shown. (D) For comparison, firing-phase distributions are shown for neurons recorded under No-MD control conditions. (E) Relationships between slow-wave FS interneuron/principal neuron firing-phase differential and post-MD plasticity in principal neurons. Values are based on the differential between firing phases of individual principal neurons and the mean firing phase of FS interneurons recorded on the same stereotrode bundle. For display purposes, data were binned in 20° intervals; mean values (±SEM) for these intervals are shown, together with a third-degree polynomial regression fit to the data points. At sites where FS interneuron firing led principal neuron firing by 60–120° during slow-wave oscillations, post-MD ODI changes in principal neurons were greatest. (F) Overview of response changes and hypothesized neural circuit changes during waking MD (Left) and post-MD sleep (Right). During waking MD, excitatory inputs to FS interneurons from open-eye–biased principal neurons are depressed, leading to decreased firing in these FS interneurons. During post-MD sleep, disinhibition leads to increased output from open-eye–biased principal neurons, which promotes postsynaptic strengthening of open-eye responses (and, thus, open-eye preference) in target neurons.