Graded defragmentation of cortical neuronal firing during recovery of consciousness in rats

Abstract

State-dependent neuronal firing patterns reflect changes in ongoing information processing and cortical function. A disruption of neuronal coordination has been suggested as the neural correlate of anesthesia. Here, we studied the temporal correlation patterns of ongoing spike activity, during a stepwise reduction of the volatile anesthetic desflurane, in the cerebral cortex of freely moving rats. We hypothesized that the recovery of consciousness from general anesthesia is accompanied by specific changes in the spatiotemporal pattern and correlation of neuronal activity. Sixty-four contact microelectrode arrays were chronically implanted in the primary visual cortex (contacts spanning 1.4-mm depth and 1.4-mm width) for recording of extracellular unit activity at four steady-state levels of anesthesia (8-2% desflurane) and wakefulness. Recovery of consciousness was defined as the regaining of the righting reflex (near 4%). High-intensity firing (HI) periods were segmented using a threshold (200-ms) representing the minimum in the neurons' bimodal interspike interval histogram under anesthesia. We found that the HI periods were highly fragmented in deep anesthesia and gradually transformed to a near-continuous firing pattern at wakefulness. As the anesthetic was withdrawn, HI periods became longer and increasingly correlated among the units both locally and across remote recording sites. Paradoxically, in 4 of 8 animals, HI correlation was also high at the deepest level of anesthesia (8%) when local field potentials (LFP) were burst-suppressed. We conclude that recovery from desflurane anesthesia is accompanied by a graded defragmentation of neuronal activity in the cerebral cortex. Hypersynchrony during deep anesthesia is an exception that occurs only with LFP burst suppression.

Keywords: anesthesia; burst suppression; consciousness; correlation; synchrony.

Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Figures

Figure 1

Multichannel spike recording and delineation high-intensity firing (HI) vs. low-intensity firing (LO) states. Multichannel recording, spike-field correlation and duration-weighted interspike-interval histogram. (A) Electrode placement of the 64-contact neural probe in the rat primary visual cortex monocular region (V1M) in the right hemisphere. Each dot represents the approximate location of an electrode contact. Schematic is overlaid on a stereotaxic drawing obtained from the Paxinos rat brain atlas (sagittal slice, 7.0 mm posterior, 3.0–3.5 mm lateral, relative to bregma). (B) Example of recorded spike waveforms from 15 channels in one experiment. Waveforms of different colors represent different sorted units. (C) Interspike interval distributions in five anesthetic conditions (8%–0% desflurane). The distributions are bimodal with a minimum near 200 ms at all anesthetic levels except at wakefulness. (D) Illustration of HI periods (red brackets) at five anesthetic conditions in the same experiment. HI periods were defined as relatively tight spike groups (minimum of 3 spikes, consecutive spikes separated by

Figure 2

Example of local field potential (LFP) and spike recordings in five conditions in the same animal. Spikes tend to group according to the negative phase of LFP under anesthesia. At 8% desflurane, LFP burst-suppression is present in this animal.

Figure 3

Spike-field correlation. (A) Cross correlogram (CCG) between LFP and spike rate at four desflurane concentrations (8%–2%) and wakefulness (0%). (B) Effect of desflurane concentration on the minimum value of the CCG. CCG and data represent mean and standard deviation from eight animals.

Figure 4

Concentration-dependent effect of desflurane on the firing properties of all recorded units. (A) Duration of high- intensity firing (HI) and low- intensity firing (LO) periods. Significant linear trends in both HI and LO duration as a function of desflurane concentration are present. (B) Average spike rates during HI/LO periods. Also shown is the average spike rate for the entire recording period (All). A significant linear trend is present in all cases. Data represent means and standard deviation.

Figure 5

Nearest neighbor correlation maps of high-intensity firing (HI) periods at four depths of anesthesia and wakefulness (8% to 0% desflurane) in eight rats. The color of each cell represents the average correlation coefficient of the respective cell with its eight neighbors (fewer neighbors at the array boundaries). Empty cells have no significant correlation. Rats 5–8 displayed burst suppression in the local field potential (LFP) at 8% desflurane that was associated with significantly higher correlation (hypersynchrony) of the HI periods.

Figure 6

Pair-wise correlation of high-intensity firing (HI) periods from all units as a function of anesthetic state. Data are shown separately for two groups of rats; those that experienced local field potential (LFP) burst suppression at 8% desflurane and those that did not. (A) Correlation among units recorded from neighboring electrode sites (data from Figure 5). (B) Correlation among units recorded at the same electrode shank. (C) Correlation among units recorded from electrode sites at the same cortical depth. In each case, correlation showed significant linear trend at between 6% and 0% desflurane. The correlation coefficients at 8% desflurane were significantly different between the two groups, suggesting hypersynchrony in the presence of burst suppression. *: p<0.001, linear trend across 8%–0% desflurane in the non-bursting group. #: p<0.05 vs. other group at 8% desflurane.

Figure 7

Correlation of high-intensity firing (HI) periods within supragranular (SG), granular (G), and infragranular (IG) layers from all experiments. A significant concentration-dependent effect of desflurane at 6% to 0% is present in the granular layer only. *: p

Figure 8

Correlation of high-intensity firing periods as a function of distance between recording sites at four anesthetic desflurane levels (8%–2%) and wakefulness (0%). (A) Pseudo-color display of correlation coefficients (CC) as a function of distance between electrode shanks at various recording depths in cortex. Values at zero distance indicate CC between units recorded at the same electrode site. (B) CC as a function of the Euclidean distance between all electrode sites. (C) Significant curve fit to data in panel B collapsed across five conditions.