Aberrant slow waves in the hippocampus during activation in mice with low cholinergic tone

Abstract

The effects of acetylcholine on cortical activation were studied in wild-type (WT) mice, compared to knockout (KO) mice depleted of the vesicular acetylcholine transporter (VAChT) gene in the basal forebrain, and knockdown (KD) mice with heterogeneous depletion of VAChT gene in the brain. Cortical activation was assessed by comparing power spectra of local field potentials (LFPs) during activated states of rapid-eye-movement sleep (REM) or walk (WLK), with those during non-activated states of slow-wave sleep (SWS) or awake-immobility (IMM). Activation-induced suppression of delta (1-4 Hz) and beta (13-30 Hz) power in the hippocampus, and delta power in frontal cortex, were reduced in KO and KD mice compared to WT mice.Mean theta frequency was higher in KD than KO mice during WLK and REM, but not different between WT and KO mice. Peak theta (4-12 Hz) and integrated gamma (30-150 Hz) power were not significantly different among mouse groups. However, theta-peak-frequency selected gamma2 (62-100 Hz) power was lower in KO than WT or KD mice during WLK, and theta-peak-frequency selected theta power during REM decreased faster with high theta frequency in KO than WT/ KD mice. Theta power increase during REM compared to WLK was lower in KO and KD mice compared to WT mice. Theta-gamma cross-frequency coherence, a measure of synchronization of gamma with theta phase, was not different among mouse groups.However, during REM, SWS, and IMM, delta-gamma coherence was significantly higher and proximal-distal delta coherence in CA1 was lower in KO than WT/KD mice. We conclude that a deficiency in basal forebrain acetylcholine release not only enhances slow waves and suppresses theta-associated gamma waves during activation, but also increases delta-gamma cross-frequency coherence during nonactivated states, with a possible effect of disrupting cognitive processing during any brain state. K E Y W O R D S delta waves, delta-gamma coupling, rapid-eye-movement sleep, slow-wave sleep, theta rhythm, theta-gamma coupling, vesicular acetylcholine transporter 1 | INTRODUCTION Cortical (hippocampal and neocortical) activation is observed electrographically as a decrease of slow waves, or desynchronization

Muscarinic and N‐methyl‐D‐aspartate receptor blockade reveal differences in hippocampal local field potentials in mice with low cholinergic tone

“…Cross‐frequency coherence (CFC) was used to estimate coherence of the amplitude of a gamma frequency band to that of a low‐frequency oscillation at an electrode (Colgin et al, 2009; Law & Leung, 2018; Leung & Chu, 2021). The LFP was FFT filtered to extract a gamma (γ1 or γ2) frequency band, inverse‐FFT filtered and Hilbert transformed to derive an amplitude envelope of the gamma band.…”

“…Coherence and phase spectra were constructed for the γ1 or γ2 amplitude envelope and the simultaneously recorded, unfiltered LFP signal; nf = 2 was used for smoothing, and values at <0.7 Hz were not smoothed. In order to determine the relation of theta power and theta‐gamma CFC with peak theta frequency, nonoverlapping short segments of approximately 1‐s duration (1024 points for 1 K sampling, or 128 points for 200‐Hz sampling) during walking were subjected to spectral analysis (Leung & Chu, 2021). All artifact‐free segments with the same peak theta frequency between 4.9 and 11.8 Hz (0.98 Hz intervals) were selected to calculate the theta‐gamma CFC spectra at a fixed peak theta‐frequency.…”

“…In particular, the occurrence of approximately seven gamma cycles within a phase of the theta rhythm may serve as computation cycles to encode or retrieve memory (Lisman & Jensen, 2013). Coupling of γ oscillation with a particular delta phase may also underlie neural processing (Bergmann & Born, 2018; Leung & Chu, 2021).…”

Medial Septum Modulates Consciousness and Psychosis-Related Behaviors Through Hippocampal Gamma Activity

“…Hippocampal activation in behaving rodents, as observed in the LFPs and evoked potentials (Leung et al, 1982 ; Leung, 1985 , 1998 ; Leung and Chu, 2021 ), ranks from low activation during slow-wave sleep and awake-immobility, intermediate activation during small (e.g., head) movements and high activation during vigorous voluntary movements (walking, turning, and rearing; Figure 1B 1). With the lowest activation, hippocampal LFPs show large irregular activity, or high-amplitude slow waves (<25 Hz) accompanied by low-amplitude gamma (30−100 Hz) activity ( Figure 1B 1; Leung, 1985 , 1998 ).…”

“…With the lowest activation, hippocampal LFPs show large irregular activity, or high-amplitude slow waves (<25 Hz) accompanied by low-amplitude gamma (30−100 Hz) activity ( Figure 1B 1; Leung, 1985 , 1998 ). Small activation decreases irregular slow waves with small or no theta and gamma increase, and high activation increases theta and gamma oscillations ( Figure 1B 1; Leung, 1985 , 1998 ; Leung and Chu, 2021 ). In the hippocampus, the residual power spectrum, or power spectrum without theta rhythm, gives a better description of the activation at low levels, since a prominent theta rhythm only accompanies moderate and high activation in rodents.…”