Delta oscillations induced by ketamine increase energy levels in sleep-wake related brain regions

Abstract

Neuronal signaling consumes much of the brain energy, mainly through the restoration of the membrane potential (MP) by ATP-consuming ionic pumps. We have reported that, compared with waking, ATP levels increase during the initial hours of natural slow-wave sleep, a time with prominent EEG delta oscillations (0.5-4.5Hz). We have hypothesized that there is a delta oscillation-ATP increase coupling, since, during delta waves, neurons exhibit a prolonged hyperpolarizing phase followed by a very brief phase of action potentials. However, direct proof of this hypothesis is lacking, and rapid changes in EEG/ neuronal activity preclude measurement in the naturally sleeping brain. Thus, to induce a uniform state with pure delta oscillations and one previously shown to be accompanied by a similar pattern of neuronal activity during delta waves as natural sleep, we used ketamine-xylazine treatment in rats. We here report that, with this treatment, the high energy molecules ATP and ADP increased in frontal and cingulate cortices, basal forebrain, and hippocampus compared with spontaneous waking. Moreover, the degree of ATP increase positively and significantly correlated with the degree of EEG delta-activity. Supporting the hypothesis of decreased ATP consumption during delta activity, the ATP-consuming Na+-K+-ATPase mRNA levels were significantly decreased whereas the mRNAs for the ATP-producing cytochrome c oxidase (COX) subunits COX III and COX IVa were unchanged. Taken together, these data support the hypothesis of a cortical delta oscillation-dependent reduction in ATP consumption, thus providing the brain with increased ATP availability, and likely occurring because of reduced Na+-K+-ATPase related energy consumption.

Computational Classification Approach to Profile Neuron Subtypes from Brain Activity Mapping Data

“…4c ). This range of increased ISIs corresponded to the Delta frequency band (1–4 Hz) 35 , as evident from the power-density analysis ( Fig. 4d ).…”

Differential Effects of an NR2B NAM and Ketamine on Synaptic Potentiation and Gamma Synchrony: Relevance to Rapid-Onset Antidepressant Efficacy

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A novel dynamic network imaging analysis method reveals aging-related fragmentation of cortical networks in mouse

“…The majority of the power is in the delta range (approximately 3 Hz) in both young and aged animals. To determine the modulation of spontaneous activity by anesthesia, mice were anesthetized with ketamine/xylazine (after spontaneous signals were measured for CommDy analysis) and we observed the expected overall decrease in frequency in both groups (p=0.006), as has been seen previously [60, 61], with no differences between groups (p=0.3, Supplemental Figure 2B). These data suggest that spontaneous flavoprotein autofluorescence signals track with more commonly-measured indicators of spontaneous activity, such as EEG, but given the slow nature of the signal are limited to lower frequency spectral bands than EEG.…”