Evaluation of Hemisphere Lateralization with Bilateral Local Field Potential Recording in Secondary Motor Cortex of Mice

Summary

We present in vivo electrophysiological recording of the local field potential (LFP) in bilateral secondary motor cortex (M2) of mice, which can be applied to evaluate hemisphere lateralization. The study revealed altered levels of synchronization between the left and right M2 in APP/PS1 mice compared to WT controls.

Abstract

This article demonstrates complete, detailed procedures for both in vivo bilateral recording and analysis of local field potential (LFP) in the cortical areas of mice, which are useful for evaluating possible laterality deficits, as well as for assessing brain connectivity and coupling of neural network activities in rodents. The pathological mechanisms underlying Alzheimer's disease (AD), a common neurodegenerative disease, remain largely unknown. Altered brain laterality has been demonstrated in aging people, but whether or not abnormal lateralization is one of the early signs of AD has not been determined. To investigate this, we recorded bilateral LFPs in 3-5-month-old AD model mice, APP/PS1, together with littermate wild type (WT) controls. The LFPs of the left and right secondary motor cortex (M2), specifically in the gamma band, were more synchronized in APP/PS1 mice than in WT controls, suggesting a declined hemispheric asymmetry of bilateral M2 in this AD mouse model. Notably, the recording and data analysis processes are flexible and easy to carry out, and can also be applied to other brain pathways when conducting experiments that focus on neuronal circuits.

Introduction

Alzheimer's disease (AD) is the most common form of dementia^1,2. Extracellular beta amyloid protein (β-amyloid protein, Aβ) deposition and intracellular neurofibrillary tangles (NFTs) are the main pathological features of AD^3,4,5, but the mechanisms underlying AD pathogenesis remain largely unclear. Cerebral cortex, a key structure in cognition and memory, is impaired in AD⁶, and motor deficits such as slow walking, difficulty navigating the environment and gait disturbances occur....

Protocol

All animals were paired-housed under standard conditions (12 h light/dark, constant temperature environment, free access to food and water) according to the Chinese Ministry of Science and Technology Laboratory Animals Guidelines and experiments were approved by the local ethical committee of Guangzhou University. This is a non-survival procedure. 

NOTE: For data shown in the representative results, APP/PS1 (B6C3-Tg (APPswe, PSEN1dE9) 85Dbo/J) double-transgenic mice and littermate wild-type (WT) controls at 3-5 months of age, were used for recordings (n = 10, per group).

1. Animal anesthesia and surgery

Results

To see whether early AD pathology impairs the capacity of hemisphere lateralization, we conducted bilateral extracellular LFP recordings in the left and right M2 of APP/PS1 mice and WT controls (aged 3-5 months), and analyzed the cross-correlation of these left and right LFPs. In WT mice, the results demonstrated that the mean correlation between left and right LFPs at positive time lags differed significantly from that at negative time lags, implicating the existence of hemispheric asymmetries in M2 areas of WT controls.......

Discussion

We report here the procedure for in vivo bilateral extracellular recording, along with analyzing the synchronization of dual-region LFP signals, which is both flexible and easy to conduct for estimating brain hemisphere lateralization, as well as the connectivity, directionality or coupling between neural activities of two brain areas. This can be widely used to reveal not only group-neuronal activities, but also some basic properties of interregional electrophysiology, especially for labs which are interested i.......

Materials

Name	Company	Catalog Number	Comments
AC/DC Differential Amplifier	A-M Systems	Model 3000
Analog Digital converter	Cambridge Electronic Design Ltd.	Micro1401
Glass borosilicate micropipettes	Nanjing spring teaching experimental equipment company	161230	Outer diameter: 1.0mm
Microelectrode puller	Narishige	PC-10
NaCl	Guangzhou Chemical Reagent Factory	7647-14-5
Pin microelectrode holder	World Precision Instruments, INC.	MEH3SW10
Spike2	Cambridge Electronic Design Ltd.
Stereomicroscope	Zeiss	435064-9020-000
Stereotaxic apparatus	RWD Life Science	68045
Urethane	Sigma-Aldrich	94300