Reply to: “Levodopa‐Induced Dyskinesia Is Mediated by Cortical Gamma Oscillations in Experimental Parkinsonism”

Background: Aluminum (Al) causes neurodegeneration and its toxic effects on cholinergic system in the brain is well documented. However, it is unknown whether and how Al changes oscillation patterns, driven by the cholinergic system, in the hippocampus. Objective: We studied acute effects of Al on nicotinic acetylcholine receptors (nAChRs)-mediated modulation of persistent gamma oscillations in the hippocampus. Method: The field potential recording was done in CA3 area of acute hippocampal slices. Results: Carbachol-induced gamma oscillation peak power increased (1.32±0.09mV2/Hz, P<0.01) in control conditions (without Al) by application of 10µM nicotine as compared to baseline value normalized to 1. This nicotine-induced facilitation of gamma oscillation peak power was found to depend on non-α7 nAChRs. In slices with Al pre-incubation for three to four hours, gamma oscillation peak power was reduced (5.4±1.8mV2/Hz, P<0.05) and facilitatory effect of nicotine on gamma oscillation peak power was blocked as compared to the control (18.06±2.1mV2/Hz) or one hour Al pre-incubated slices (11.3±2.5mV2/Hz). Intriguingly wash-out, after three to four hours of Al incubation, failed to restore baseline oscillation power and its facilitation by nicotine as no difference was observed in gamma oscillation peak power between Al wash-out slices (3.4±1.1mV2/Hz) and slices without washout (3.6±0.9mV2/Hz). Conclusion: This study shows that at cellular level, exposure of hippocampal tissue to Al compromised nAChR-mediated facilitation of cholinergic hippocampal gamma oscillations. Longer in vitro Al exposure caused permanent changes in hippocampal oscillogenic circuitry and changed its sensitivity to nAChR-modulation. This study will help to understand the possible mechanism of cognitive decline induced by Al.

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Impaired spike-gamma coupling of area CA3 fast-spiking interneurons as the earliest functional impairment in the AppNL-G-F mouse model of Alzheimer’s disease

Molecular Psychiatry ◽

10.1038/s41380-021-01257-0 ◽

2021 ◽

Author(s):

Luis Enrique Arroyo-García ◽

Arturo G. Isla ◽

Yuniesky Andrade-Talavera ◽

Hugo Balleza-Tapia ◽

Raúl Loera-Valencia ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mouse Model ◽

Functional Impairment ◽

Amyloid Β ◽

Gamma Oscillations ◽

Gamma Oscillation ◽

Gamma Rhythm ◽

Fast Spiking

AbstractIn Alzheimer’s disease (AD) the accumulation of amyloid-β (Aβ) correlates with degradation of cognition-relevant gamma oscillations. The gamma rhythm relies on proper neuronal spike-gamma coupling, specifically of fast-spiking interneurons (FSN). Here we tested the hypothesis that decrease in gamma power and FSN synchrony precede amyloid plaque deposition and cognitive impairment in AppNL-G-F knock-in mice (AppNL-G-F). The aim of the study was to evaluate the amyloidogenic pathology progression in the novel AppNL-G-F mouse model using in vitro electrophysiological network analysis. Using patch clamp of FSNs and pyramidal cells (PCs) with simultaneous gamma oscillation recordings, we compared the activity of the hippocampal network of wild-type mice (WT) and the AppNL-G-F mice at four disease stages (1, 2, 4, and 6 months of age). We found a severe degradation of gamma oscillation power that is independent of, and precedes Aβ plaque formation, and the cognitive impairment reported previously in this animal model. The degradation correlates with increased Aβ1-42 concentration in the brain. Analysis on the cellular level showed an impaired spike-gamma coupling of FSN from 2 months of age that correlates with the degradation of gamma oscillations. From 6 months of age PC firing becomes desynchronized also, correlating with reports in the literature of robust Aβ plaque pathology and cognitive impairment in the AppNL-G-F mice. This study provides evidence that impaired FSN spike-gamma coupling is one of the earliest functional impairment caused by the amyloidogenic pathology progression likely is the main cause for the degradation of gamma oscillations and consequent cognitive impairment. Our data suggests that therapeutic approaches should be aimed at restoring normal FSN spike-gamma coupling and not just removal of Aβ.

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Superimposed gratings induce diverse response patterns of gamma oscillations in primary visual cortex

Scientific Reports ◽

10.1038/s41598-021-83923-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Bin Wang ◽

Chuanliang Han ◽

Tian Wang ◽

Weifeng Dai ◽

Yang Li ◽

...

Keyword(s):

Visual Cortex ◽

Primary Visual Cortex ◽

Field Potential ◽

Gamma Oscillations ◽

Neural Mechanisms ◽

Model Parameters ◽

Response Patterns ◽

Region Difference ◽

High Gamma ◽

Spiking Activity

AbstractStimulus-dependence of gamma oscillations (GAMMA, 30–90 Hz) has not been fully understood, but it is important for revealing neural mechanisms and functions of GAMMA. Here, we recorded spiking activity (MUA) and the local field potential (LFP), driven by a variety of plaids (generated by two superimposed gratings orthogonal to each other and with different contrast combinations), in the primary visual cortex of anesthetized cats. We found two distinct narrow-band GAMMAs in the LFPs and a variety of response patterns to plaids. Similar to MUA, most response patterns showed that the second grating suppressed GAMMAs driven by the first one. However, there is only a weak site-by-site correlation between cross-orientation interactions in GAMMAs and those in MUAs. We developed a normalization model that could unify the response patterns of both GAMMAs and MUAs. Interestingly, compared with MUAs, the GAMMAs demonstrated a wider range of model parameters and more diverse response patterns to plaids. Further analysis revealed that normalization parameters for high GAMMA, but not those for low GAMMA, were significantly correlated with the discrepancy of spatial frequency between stimulus and sites’ preferences. Consistent with these findings, normalization parameters and diversity of high GAMMA exhibited a clear transition trend and region difference between area 17 to 18. Our results show that GAMMAs are also regulated in the form of normalization, but that the neural mechanisms for these normalizations might differ from those of spiking activity. Normalizations in different brain signals could be due to interactions of excitation and inhibitions at multiple stages in the visual system.

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