Reduction of EEG theta power and changes in motor activity in rats treated with ceftriaxone

Abstract

The glutamate transporter GLT-1 is responsible for the largest proportion of total glutamate transport. Recently, it has been demonstrated that ceftriaxone (CEF) robustly increases GLT-1 expression. In addition, physiological studies have shown that GLT-1 up-regulation strongly affects synaptic plasticity, and leads to an impairment of the prepulse inhibition, a simple form of information processing, thus suggesting that GLT-1 over-expression may lead to dysfunctions of large populations of neurons. To test this possibility, we assessed whether CEF affects cortical electrical activity by using chronic electroencephalographic (EEG) recordings in male WKY rats. Spectral analysis showed that 8 days of CEF treatment resulted in a delayed reduction in EEG theta power (7-9 Hz) in both frontal and parietal derivations. This decrease peaked at day 10, i.e., 2 days after the end of treatment, and disappeared by day 16. In addition, we found that the same CEF treatment increased motor activity, especially when EEG changes are more prominent. Taken together, these data indicate that GLT-1 up-regulation, by modulating glutamatergic transmission, impairs the activity of widespread neural circuits. In addition, the increased motor activity and prepulse inhibition alterations previously described suggest that neural circuits involved in sensorimotor control are particularly sensitive to GLT-1 up-regulation.

Figure 1. Lack of pathological elements after ceftriaxone treatment.

A. Schematic description of electrodes location. B. Saline and CEF Treatment schedule. Day 0 represents the baseline. C. Waking absolute spectra, raw EEG and EMG signals of baseline, day 10 and day 16. Signals appeared stable across the entire length of the experiment and the signal quality was not affected by CEF treatment.

Figure 2. Power spectra analysis following ceftriaxone administration.

A. Reduction in theta power at day 10. Waking mean absolute power spectra of Day 0 and Day 10 for frontal (above) and parietal (below) EEG channel. B. Power spectra analysis relative to the baseline illustrating a reduction of theta power at Day 10 (shown in detail for single animals in the small inset) and a return to the baseline eight days after CEF withdrawal (Day 16) in frontal (above) and parietal (below) EEG channels. Statistical significance (p<0.05) is represented by black dots. Values are mean ± sem. C. Time course analysis of relative spectra (7–9 Hz frequency band) showing a significant reduction of theta power for frontal and parietal channels two days (Day 10) and four days (Day 12) after CEF withdrawal compared to the baseline (Day 0). *p<0.05. Values are mean ± sem. D. Example of power spectrum relative to the baseline for a representative animal during the entire length of the experiment. E. Frontal and parietal relative spectra showing a broad band (7–13 Hz) reduction in power during NREM sleep at day 10. Statistical significance (p<0.05) is represented by black dots. Values are mean ± sem. F. Frontal and parietal relative spectra showing a reduction in theta power during REM sleep at day 10. Statistical significance (p<0.05) is represented by black dots. Values are mean ± sem.

Figure 3. Effects of ceftriaxone treatment on motor activity.

A. Time-course of the amount of time expressed in 4s epochs spent in waking, NREM and REM sleep. Values are expressed as mean ± sem. B. Example of EMG activity during the entire length of the experiments. Note the intense activity after the end of CEF treatment. The grey line represents the threshold above and below which the motor activity is identified as active waking or quiet waking, respectively. C–D. Quantitative analysis of EMG activity (C) and Motion activity (D) during active and quiet waking for light and dark periods. Values are relative to the baseline (day 0) and expressed as mean ± sem. * (p<0.05), ** (p<0.01). E–F. Negative correlation between the time-course of relative theta power and the EMG (E) or Motion activity (F).