Functional development of large-scale sensorimotor cortical networks in the brain

Abstract

Large-scale neuronal networks integrating several cortical areas mediate the complex functions of the brain such as sensorimotor integration. Little is known about the functional development of these networks and the maturational processes by which distant networks become functionally connected. We addressed this question in the postnatal rat sensorimotor system. Using epicranial multielectrode grids that span most of the cortical surface and intracortical electrodes, we show that sensory evoked cortical responses continuously maturate throughout the first 3 weeks with the strongest developmental changes occurring in a very short time around postnatal day 13 (P13). Before P13, whisker stimulation evokes slow, initially surface-negative activity restricted mostly to the lateral parietal area of the contralateral hemisphere. In a narrow time window of ∼48 h around P13, a new early, sharp surface-positive component emerges that coincides with subsequent propagation of activity to sensory and motor areas of both hemispheres. Our data show that this new component developing at the end of the second week corresponds principally to functional maturation of the supragranular cortical layers and appears to be crucial for the functional associations in the large-scale sensorimotor cortical network. It goes along with the onset of whisking behavior, as well as major synaptic and functional changes within the S1 cortex that are known to develop during this period.

Figure 1.

Postnatal development of somatosensory evoked potentials in response to whisker deflection from P7 to P21. A, Design of the epicranial recording setup. Under isoflurane anesthesia, a multielectrode grid is placed in contact with the skull and SEPs are recorded in response to upward deflections of all whiskers on one side of the face. The position of the electrodes on the skull is schematized on the right diagram. B, Superimposed grand average SEPs from all electrodes recorded at P7 (n = 12), P10 (n = 11), P13 (n = 11), P16 (n = 7), and P21 (n = 13), illustrating the progressive modifications of the SEP waveforms during the postnatal period.

Figure 2.

Postnatal changes in the periods of significant evoked responses at epicranial electrodes. Point-wise paired t tests were applied in each age group (same groups as for Fig. 1). In each panel, uppermost electrodes correspond to the contralateral hemisphere, while lowermost electrodes correspond to the ipsilateral hemisphere. Electrodes whose coordinates correspond to the S1 and frontal cortices are labeled. Blue, t test significant periods during which the grand average SEP is lower than the prestimulus baseline; red, periods during which it is higher. Each panel is presented with the corresponding superimposed grand average.

Figure 3.

Postnatal development of SEP topographies. Segments identified by k-mean clustering segmentations indicated on the grand average GFP and corresponding mean topographic maps. Maps were calculated as average potential values during the segment period at each electrode and interpolated with Delaunay triangulations for graphical representations. Mean onset latencies below each map were calculated by fitting back individual SEPs to the clustered maps. Color scaling in microvolts is indicated at each age.

Figure 4.

A short-latency positive component appears between P12 and P14. a, Voltage maps at selected time points in response to left-sided whisker deflections recorded in the same animal at P12, P13, and P14. Color scaling in microvolts is indicated at each age. b, SEP waveforms recorded at each age from the electrode positioned above the parietal region contralateral to the stimulus (open circles in a). c, Correlation analysis in all P13 animals (n = 11) between the early parietal positive peak amplitude, calculated as the sum of the voltages recorded at the S1 electrode at each time bin across the duration of the positive component, and the total absolute activations at the electrodes located in the frontal area and in the parietal and frontal areas of the other hemisphere summated from 20 to 100 ms poststimulus. The linear regression line is illustrated (regression coefficient = 0.64).

Figure 5.

Recordings of the laminar activity profiles and CSD analyses. a, Design of the intracortical recording setup. To study sensory evoked processing in contralateral and ipsilateral cortices, recordings were made in the right hemispheres with 16-electrode probes in response to left (contralateral) and right (ipsilateral) whisker stimulations. Electrode positions are illustrated on the photomicrograph of a Nissl-stained coronal section of S1. The cortical thickness was sampled in two successive overlapping recordings allowing us to record 500 μm deeper (gray dots; see Materials and Methods). The epipial electrode (red) was not included in the CSD calculation. b, c, Epicranial, epipial, and intracortical recordings in response to contralateral (b) and ipsilateral (c) whisker stimulations in the S1 area of a P21 animal. The left panels show the intracortical LFP and the right panels the corresponding CSD traces, superimposed on color-coded plots of the interpolated CSD values. To ease comparisons between surface and deep recordings, dashed lines were placed at the onset and offset of the initial epicranial positive components determined directly on the waveforms. On the y-axis are indicated cortical depths in micrometers and cortical layer borders.

Figure 6.

Current source-density analysis of intracortical responses to whisker stimulation at P10 and P21. a, b, Grand average current-source densities of 8 animals at P10 (a) and 8 animals at P21 (b) processed in the frontal and S1 regions in response to contralateral and ipsilateral stimulations. The color-coded scale is ± 80 mV/mm². The y-axis conventions are as in Figure 5.

Figure 7.

Correlation between epicranial SEPs and intracortical CSDs in S1 at P10 and P21. a, b, Colored segments indicate periods of significant evoked CSD signal at p < 0.01 at each electrode in P10 (a) and P21 (b) rats, superimposed on the CSD traces (point-wise paired t tests with Bonferroni corrections). Above each panel are presented the grand average SEPs recorded in the same rats (P10, n = 8; P21, n = 8). Dashed lines point to onsets and offsets of the first SEP components approximate from the grand average waveforms. The y-axis indicates the cortical layer borders.

Figure 8.

Laminar LFP and MUA in the S1 cortex at P10 (top row) and at P21 (bottom row). a, b and d, e, Example voltage traces in a P10 and a P21 rat, respectively, recorded in response to a single sweep contralateral whisker deflection and showing the low (LFP; calibration, 1 mV)- and high (MUA without rectification; calibration, 50 μV)-frequency components of the poststimulus responses. The five deepest were recorded during a different sweep from that in the upper traces. c, f, Grand average MUAs (black traces; calibration 1mV²) and interpolated CSD contour plots at P10 (n = 4) and P21 (n = 4). The y-axis conventions are as in Figure 5.