Long-term plasticity in mouse sensorimotor circuits after rhythmic whisker stimulation

Abstract

Mice actively explore their environment by rhythmically sweeping their whiskers. As a consequence, neuronal activity in somatosensory pathways is modulated by the frequency of whisker movement. The potential role of rhythmic neuronal activity for the integration and consolidation of sensory signals, however, remains unexplored. Here, we show that a brief period of rhythmic whisker stimulation in anesthetized mice resulted in a frequency-specific long-lasting increase in the amplitude of somatosensory-evoked potentials in the contralateral primary somatosensory (barrel) cortex. Mapping of evoked potentials and intracortical recordings revealed that, in addition to potentiation in layers IV and II/III of the barrel cortex, rhythmic whisker stimulation induced a decrease of somatosensory-evoked responses in the supragranular layers of the motor cortex. To assess whether rhythmic sensory input-based plasticity might arise in natural settings, we exposed mice to environmental enrichment. We found that it resulted in somatosensory-evoked responses of increased amplitude, highlighting the influence of previous sensory experience in shaping sensory responses. Importantly, environmental enrichment-induced plasticity occluded further potentiation by rhythmic stimulation, indicating that both phenomena share common mechanisms. Overall, our results suggest that natural, rhythmic patterns of whisker activity can modify the cerebral processing of sensory information, providing a possible mechanism for learning during sensory perception.

Figure 1.

A 10 min period of 8 Hz rhythmic whisker stimulation induces a long-lasting plasticity of whisker-evoked brain responses. A, Top, Epicranial SEP recording setup. Anesthetized mice were placed in a stereotaxic frame; the scalp was retracted, and an array of 5–32 electrodes (black dots) was applied to the skull bones. These electrodes recorded potentials evoked by mechanical deflection of all large facial whiskers on the contralateral snout. The electrode recording the earliest-latency, largest-amplitude SEP (larger black dot) was used for analysis. Bottom, Rhythmic stimulation paradigm. Three baseline SEPs were recorded at 10 min intervals. The whiskers were then rhythmically deflected at a frequency of 8 Hz for 10 min, after which SEP were again recorded every 10 min for 90 min. In controls, the stimulator was activated for 10 min at 8 Hz close to the whiskers without making contact with them (sham stimulation). B, Examples of SEP waveforms recorded over the barrel cortex at baseline (dotted trace) and 30 min after a 10 min period of 8 Hz whisker stimulation (solid trace). C, Time course of SEP peak-to-peak averages before and after 8 Hz stimulation (stim; n = 5) or sham stimulation (control; n = 5). D, Pooled averages of the SEP peak-to-peak from the three baseline recordings and the recordings made between 10 and 30, between 40 and 60, and between 70 and 90 min after 8 Hz whisker stimulation. E, Examples of SEP waveforms recorded over the barrel cortex at baseline and after rhythmic whisker stimulation at 2 Hz (left) or 20 Hz (right). F, Pooled averages of the SEP amplitudes from the three baseline recordings and the recordings made between 20 and 50 min after the stimulation period. Significant difference from baseline at **p < 0.01 or at ***p < 0.001.

Figure 2.

A 10 min period of 8 Hz rhythmic whisker stimulation induces a long-lasting and input-specific potentiation of whisker-evoked brain responses under isoflurane anesthesia. A, Examples of SEP waveforms (n = 8) recorded under isoflurane anesthesia over the left and right barrel cortices in responses to respective contralateral deflections 20 min before (baseline) and 60 min after (post-stim) 8 Hz (right) whisker stimulation. B, Pooled averages of the SEP amplitudes from the three baseline and 30, 60, and 90 min after 8 Hz whisker stimulation, normalized against the baseline. Asterisks indicate significant differences with baseline at p < 0.05. Potentiated responses are limited to the left barrel cortex, contralateral to the 8 Hz whisker stimulation.

Figure 3.

Rhythmic whisker stimulation induces long-lasting potentiation of whisker-evoked current sinks in the barrel cortex. A, Examples of whisker-evoked LFP recordings in the barrel cortex (left; n = 5 mice) and CSD profiles (right) in the test group at baseline (black traces) and 60 min after 8 Hz whisker stimulation (red traces). Positive LFP voltages and CSD sources are upward going. Roman numerals indicate the approximate limits of cortical layers. Calibration: LFP, 250 μV; CSD, 25 mV/mm². B, Examples of whisker-evoked LFP recordings (n = 5 mice) and CSD profiles in the control group at baseline and 60 min after sham whisker stimulation. Calibration as in A. C, Averages of selected current sink peak amplitudes at four selected electrodes recorded 30, 60, and 90 min after 8 Hz whisker stimulation, normalized against the baseline. Insets show the averaged CSD traces at the superficial layer II–III, deep layer II–III, layer IV, and layer V–VI border at baseline and 30, 60, and 90 min after 8 Hz stimulation. Traces from controls are not shown. Calibration: horizontal, 10 ms; vertical, 10 mV/mm² for superficial and deep LII–III and LIV, 2.5 mV/mm² for LV–VI border. Significant difference from baseline at *p < 0.05 or at **p < 0.01 (double).

Figure 4.

Rhythmic whisker stimulation induces a long-lasting plasticity of the topography of whisker-evoked multichannel brain responses. A, Topographic maps of the averaged SEP at baseline (top) and 40–60 min after rhythmic whisker stimulation (bottom). B, Topographic maps of the averaged SEP at baseline and 40–60 min after sham stimulation in controls. C, Results of the randomization procedure for topographic dissimilarity between SEP recorded at baseline and 40–60 min after 8 Hz whisker stimulation. 1-p values are plotted at each time point (5 time points per millisecond). D, Results of the randomization procedure for topographic dissimilarity in sham-stimulated controls. E, Topographic maps (determined by an electrode-wise randomization procedure) of the directions of significant voltage differences at each electrode between the SEP at baseline and 40–60 min after stimulation during the periods of significant differences in map topography. Red color indicates larger voltage values, whereas blue color indicates smaller voltage values after stimulation compared with baseline.

Figure 5.

Rhythmic whisker stimulation induces long-lasting depression of whisker-evoked current sinks in the motor cortex. A, Examples of whisker-evoked LFP recordings in the motor cortex (left; n = 4 mice) and CSD profiles (right) in the test group at baseline (black traces) and 60 min after 8 Hz whisker stimulation (red traces). Positive LFP voltages and CSD sources are upward going. Roman numerals indicate the approximate limits of cortical layers. Calibration: LFP, 50 μV; CSD, 5 mV/mm². B, Examples of whisker-evoked LFP recordings (n = 5 mice) and CSD profiles in the control group at baseline and 60 min after sham whisker stimulation. Calibration as in A. C, Averages of the current sink peak amplitude in deep layer II–III recorded 30, 60, and 90 min after 8 Hz whisker stimulation, normalized against the baseline. Inset shows the averaged CSD trace in deep layer II–III at baseline and 30, 60, and 90 min after 8 Hz stimulation. Traces from controls are not shown. Calibration: horizontal, 10 ms; vertical, 2.5 mV/mm².

Figure 6.

Changes in environmental conditions induce a reversible plasticity of whisker-evoked electrical brain responses. A, Environmental enrichment paradigm. In one group, mice were housed alone in a standard cage for 3 weeks, after which the first SEP was recorded; mice were then housed in enriched cages for another 3 weeks, and the second SEP was recorded. In another group, mice were housed first in the rich and then in the poor environment. B, Examples of SEP waveforms recorded over the barrel cortex in mice housed first in poor environment (solid trace) and then in a rich environment (dotted trace). C, Examples of SEP waveforms in mice housed first in a rich environment (solid trace) and then in a poor environment (dotted trace). D, Averages of the SEP amplitudes of the first and second recordings for the four experimental groups. E, Examples of SEP waveforms recorded over the barrel cortex at baseline and after rhythmic 8 Hz whisker stimulation in mice previously housed in a poor environment (left; same dataset as in Fig. 1) or a rich environment (right). F, Pooled averages of the SEP amplitudes from the three baseline recordings and the recordings made between 20 and 50 min after a 10 min period of 8 Hz whisker stimulation in mice previously housed in a poor or a rich environment.