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And explore the mysteries of neuroscience with rigorous academic and logical thinking.
Written by Yang Li, edited by Wang Sizhen, Alzheimer's disease (AD), commonly known as Alzheimer's disease, is the most common dementia.
As of 2019, there are more than 10 million AD patients in my country.
Currently, there are no drugs that can effectively treat AD.
Therefore, there is an urgent need to find some non-invasive, convenient and low-cost early warning markers for AD that can be used before clinical dementia symptoms as indicators for early screening and investigation, and use this as a target for research and development Drugs that can delay or even prevent the occurrence of dementia.
Although other sensory functions may also change in AD, abnormal olfactory function is the most likely early warning marker to predict the occurrence of AD [1].
However, the mechanism relationship between electrophysiological, biochemical and behavioral phenomena of abnormal olfactory function is still unclear.
Professor Yang Li’s research group from the School of Life Sciences, Guangzhou University has long been committed to revealing: (1) the pathological mechanism and early biomarkers of the neurodegenerative disease Alzheimer’s disease; (2) β-amyloid precursor (APP) The neuron and synaptic functions of humans; and (3) the neurobiological basis of emotions and social behaviors.
On March 4, 2021, Yang Li’s group published a research paper entitled Enhancing GABAergic signaling ameliorates aberrant gamma oscillations of olfactory bulb in AD mouse models in Molecular Neurodegeneration, revealing the important molecules, cells and nerves of olfactory abnormalities in the early stages of AD.
Circuit mechanisms and potential therapeutic targets.First, the researchers found that AD model mice (APP/PS1 and 3xTg) have a reduced ability to perceive odors at the age of 3-5 months when there is no AD pathological marker Aβ amyloid plaque and no learning and memory abnormalities.
Because the olfactory epithelium (OE), the olfactory bulb (OB) [2] and the pear-shaped cortex (PC) convert chemical odors into action potentials on olfactory sensory neurons (OSNs), encode olfactory electrical signals, and finally form The important brain structure of smell.
Therefore, immediately afterwards, the researchers conducted research on the mechanism.
The results showed that at the molecular level, the significant up-regulation of α1 and β3 subreceptor protein expression of the olfactory bulb inhibitory postsynaptic receptor GABAAR is a common feature of APP/PS1 and 3xTg AD mice; at the cellular level, mature olfactory sensation in the olfactory epithelium The number of neurons decreases, and the amplitude of the electroolfactory (EOG) induced by smell decreases.
These results suggest that odor molecules have fewer action potentials in the olfactory epithelium of AD mice, and the excitatory impulse of olfactory sensory neurons to the olfactory bulb is reduced.
At the same time, whole-cell patch clamp and local field potential recording experiments found that the GABAergic inhibitory postsynaptic current (IPSC) of APP/PS1 mouse olfactory bulb main cell (M/T) and the inhibitory postsynaptic potential of the dendritic region ( IPSP) increases, and the P2/P1 ratio of IPSC induced by double pulse stimulation decreases, which implies that the transmitter release probability (Pr) of the GABA interneuron (IN) terminal is up-regulated.
In addition, in response to the decrease in the number of olfactory sensory neurons in the olfactory epithelium and the decrease in the amplitude of the olfactory electrogram, those excitatory postsynaptic potentials in the dendritic area of the main cell of the olfactory bulb that can receive excitatory projections from olfactory sensory neurons ( EPSP) decreased, and the excitement/inhibition ratio (E/I) also decreased.
Gamma oscillation (ie gamma wave) is one of the basic waveforms of human brain waves.
It is produced by the activation of neural circuits composed of excitatory and inhibitory interneurons.
It has been proven to be a necessary component for advanced cognitive functions and sensory processing; And gamma rhythm can recruit neurons and glial responses, thereby attenuating AD-related pathology [3-4]. Theta oscillation (theta wave) is also one of the basic waveforms of human brain waves, and is considered to be a neural information processing mechanism in advanced cognitive processes such as sensory processing and learning and memory, attention, and motivation [5-6] .
Here, the researchers found that the gamm oscillation of the olfactory bulb increased, and the theta oscillation, which can reflect the electrical signal intensity of the olfactory epithelium → the olfactory bulb, was weakened.
Moreover, the number of c-fos-positive neurons in the anterior piriform cortex of the olfactory advanced center of APP/PS1 mice cut back.
These results indicate that the neuronal activity of the anterior piriform cortex is reduced, and it is speculated that the decrease of excitatory afferents from the olfactory bulb→the anterior piriform cortex may be one of the important reasons for the decreased activity of such neurons.
In view of the fact that gamma oscillation is the brain electrical expression form of distinguishing odor and processing and encoding olfactory information [3].
Therefore, next, the author conducted a dual-channel local field potential recording experiment, and the results showed that the synchronization of the gamma oscillations of the olfactory bulb and the pre-pyriform cortex at the loop level was reduced, and theta-gamma coupling was weakened.
These results further indicate the abnormality of neuronal activity between the anterior piriform cortex and the olfactory bulb, and also prove the author's speculation.
At the end of the article, it is interesting that the researchers found that the anti-epileptic clinical drug Tiagabine (i.
e.
tiagabine, also known as tiagabine) can improve the upregulated GABAAR in the olfactory bulb by inhibiting the reabsorption of the GABA transmitter in the synaptic cleft.
The α1 and β3 subreceptors are expressed, and the abnormally increased gamma oscillation is reduced.
In general, this study suggests that olfactory-related EEG abnormalities may be a convenient, non-invasive, and low-cost detection indicator that can be used for early clinical investigation of AD.
The study also suggests that GABA signaling pathways are used as targets to enhance GABA.
It can inhibit the synaptic transmission and achieve the AD prevention and treatment strategy to improve the early symptoms of AD, especially the abnormal smell.
Paper summary picture (picture quoted from: Chen et al.
Molecular Neurodegeneration 2021; 16:14) Chen Ming (front row, second from left), Yang Li (front row, middle) (picture source: Yang Li laboratory) Guangzhou University for the article The first completed unit. Ming Chen (current working unit is Anhui Medical University), Yunan Chen (currently a PhD student in the International Max Planck School of Intelligent System Research) and Qingwei Huo (current working unit is Guangzhou University of Chinese Medicine) are the co-first authors of this article .
Professor Yang Li of Guangzhou University is the corresponding author of the article.
The research group of Professor Long Cheng from South China Normal University is a cooperative unit.
The research was funded by the National Natural Science Foundation of China (31771219, 81801064, 81804197, 31871170, 31970915), the major science and technology project of Guangdong Brain Science and Brain-inspired Research (2018B030336001), and the Guangzhou University Hundred Talents Program Startup Fund.
Original link: https://molecularneurodegeneration.
biomedcentral.
com/articles/10.
1186/s13024-021-00434-7 Recommended high-quality scientific research training courses [1] Multi-omics data integration mining and analysis (web) seminar (March 12- 14th, two days and two nights) [2] Patch Clamp and Optogenetics and Calcium Imaging Technology Seminar (February 27-28, 21) (April-May 2020 courses can be booked) [3] Online ︱ Order Symposium on Cell Sequencing Data Analysis and Research Ideas (January 16-17, 21) (can be booked for February-March 2021) [4] Online Course︱ "Scientific Research Image Processing and Mapping" January 23/ 24/26/28 (can be booked for February-March 2021) [5] R language data analysis practical technology (web) seminar (December 26-27, 2020) (can be booked for 2-3, 2020 Monthly course) [6] Data analysis and essay writing training of imaging omics, basic practical training class of MRI brain imaging data processing (imagingology: January 16-17 MRI: January 23-24) (available Book the course from February to March 2020) [7] Thesis illustration, mechanism pattern diagram, scientific research data processing, statistical analysis and chart production and drawing special class (map service provided after class, January 23-24, 30-31 online class ( Available to book courses from February to March 2020) References (swipe up and down to view) [1] Murphy C.
Olfactory and other sensory impairments in Alzheimer disease.
Nat Rev Neurol.
2019; 15: 11–24.
[2] Tan Jie, Luo Minmin.
The processing of olfactory information by the olfactory bulb, Chinese Journal of Biophysics.
2010; 26 (3): 194-208.
[3] Lepousez G, Lledo PM.
Odor discrimination requires proper olfactory fast oscillations in awake mice.
Neuron.
2013; 80: 1010-1024.
【4】Iaccarino HF, Singer AC, Martorell AJ,Rudenko A, Gao F, Gillingham TZ, Mathys H, Seo J, Kritskiy O, Abdurrob F, Adaikkan C, Canter CG.
Rueda R, Emery N.
Brown EN, Boyden ES, Tsai LH.
Gamma frequency entrainment attenuates amyloid load and modifies microglia.
Nature.
2016; 540: 230–235.
[5] Wang D, Clouter A, Chen Q, Kimron L.
Hanslmayr S.
Single-trial phase entrainment of theta oscillations in sensory regions predicts human associative memory performance.
J Neurosci.
2018; 38: 6299-6309.
[6] Nora A.
Herweg, Ethan A.
Solomon, Michael J.
Kahana 1.
Theta oscillations in human memory.
Trends in Cognitive Sciences, 2020; 24: 3.
Plate making︱Wang Sizhen End of this article230–235.
[5] Wang D, Clouter A, Chen Q, Kimron L.
Hanslmayr S.
Single-trial phase entrainment of theta oscillations in sensory regions predicts human associative memory performance.
J Neurosci.
2018; 38: 6299-6309.
[6] Nora A.
Herweg, Ethan A.
Solomon, Michael J.
Kahana 1.
Theta oscillations in human memory.
Trends in Cognitive Sciences, 2020; 24: 3.
Plate making︱Wang Sizhen End of this article230–235.
[5] Wang D, Clouter A, Chen Q, Kimron L.
Hanslmayr S.
Single-trial phase entrainment of theta oscillations in sensory regions predicts human associative memory performance.
J Neurosci.
2018; 38: 6299-6309.
[6] Nora A.
Herweg, Ethan A.
Solomon, Michael J.
Kahana 1.
Theta oscillations in human memory.
Trends in Cognitive Sciences, 2020; 24: 3.
Plate making︱Wang Sizhen End of this article
Written by Yang Li, edited by Wang Sizhen, Alzheimer's disease (AD), commonly known as Alzheimer's disease, is the most common dementia.
As of 2019, there are more than 10 million AD patients in my country.
Currently, there are no drugs that can effectively treat AD.
Therefore, there is an urgent need to find some non-invasive, convenient and low-cost early warning markers for AD that can be used before clinical dementia symptoms as indicators for early screening and investigation, and use this as a target for research and development Drugs that can delay or even prevent the occurrence of dementia.
Although other sensory functions may also change in AD, abnormal olfactory function is the most likely early warning marker to predict the occurrence of AD [1].
However, the mechanism relationship between electrophysiological, biochemical and behavioral phenomena of abnormal olfactory function is still unclear.
Professor Yang Li’s research group from the School of Life Sciences, Guangzhou University has long been committed to revealing: (1) the pathological mechanism and early biomarkers of the neurodegenerative disease Alzheimer’s disease; (2) β-amyloid precursor (APP) The neuron and synaptic functions of humans; and (3) the neurobiological basis of emotions and social behaviors.
On March 4, 2021, Yang Li’s group published a research paper entitled Enhancing GABAergic signaling ameliorates aberrant gamma oscillations of olfactory bulb in AD mouse models in Molecular Neurodegeneration, revealing the important molecules, cells and nerves of olfactory abnormalities in the early stages of AD.
Circuit mechanisms and potential therapeutic targets.First, the researchers found that AD model mice (APP/PS1 and 3xTg) have a reduced ability to perceive odors at the age of 3-5 months when there is no AD pathological marker Aβ amyloid plaque and no learning and memory abnormalities.
Because the olfactory epithelium (OE), the olfactory bulb (OB) [2] and the pear-shaped cortex (PC) convert chemical odors into action potentials on olfactory sensory neurons (OSNs), encode olfactory electrical signals, and finally form The important brain structure of smell.
Therefore, immediately afterwards, the researchers conducted research on the mechanism.
The results showed that at the molecular level, the significant up-regulation of α1 and β3 subreceptor protein expression of the olfactory bulb inhibitory postsynaptic receptor GABAAR is a common feature of APP/PS1 and 3xTg AD mice; at the cellular level, mature olfactory sensation in the olfactory epithelium The number of neurons decreases, and the amplitude of the electroolfactory (EOG) induced by smell decreases.
These results suggest that odor molecules have fewer action potentials in the olfactory epithelium of AD mice, and the excitatory impulse of olfactory sensory neurons to the olfactory bulb is reduced.
At the same time, whole-cell patch clamp and local field potential recording experiments found that the GABAergic inhibitory postsynaptic current (IPSC) of APP/PS1 mouse olfactory bulb main cell (M/T) and the inhibitory postsynaptic potential of the dendritic region ( IPSP) increases, and the P2/P1 ratio of IPSC induced by double pulse stimulation decreases, which implies that the transmitter release probability (Pr) of the GABA interneuron (IN) terminal is up-regulated.
In addition, in response to the decrease in the number of olfactory sensory neurons in the olfactory epithelium and the decrease in the amplitude of the olfactory electrogram, those excitatory postsynaptic potentials in the dendritic area of the main cell of the olfactory bulb that can receive excitatory projections from olfactory sensory neurons ( EPSP) decreased, and the excitement/inhibition ratio (E/I) also decreased.
Gamma oscillation (ie gamma wave) is one of the basic waveforms of human brain waves.
It is produced by the activation of neural circuits composed of excitatory and inhibitory interneurons.
It has been proven to be a necessary component for advanced cognitive functions and sensory processing; And gamma rhythm can recruit neurons and glial responses, thereby attenuating AD-related pathology [3-4]. Theta oscillation (theta wave) is also one of the basic waveforms of human brain waves, and is considered to be a neural information processing mechanism in advanced cognitive processes such as sensory processing and learning and memory, attention, and motivation [5-6] .
Here, the researchers found that the gamm oscillation of the olfactory bulb increased, and the theta oscillation, which can reflect the electrical signal intensity of the olfactory epithelium → the olfactory bulb, was weakened.
Moreover, the number of c-fos-positive neurons in the anterior piriform cortex of the olfactory advanced center of APP/PS1 mice cut back.
These results indicate that the neuronal activity of the anterior piriform cortex is reduced, and it is speculated that the decrease of excitatory afferents from the olfactory bulb→the anterior piriform cortex may be one of the important reasons for the decreased activity of such neurons.
In view of the fact that gamma oscillation is the brain electrical expression form of distinguishing odor and processing and encoding olfactory information [3].
Therefore, next, the author conducted a dual-channel local field potential recording experiment, and the results showed that the synchronization of the gamma oscillations of the olfactory bulb and the pre-pyriform cortex at the loop level was reduced, and theta-gamma coupling was weakened.
These results further indicate the abnormality of neuronal activity between the anterior piriform cortex and the olfactory bulb, and also prove the author's speculation.
At the end of the article, it is interesting that the researchers found that the anti-epileptic clinical drug Tiagabine (i.
e.
tiagabine, also known as tiagabine) can improve the upregulated GABAAR in the olfactory bulb by inhibiting the reabsorption of the GABA transmitter in the synaptic cleft.
The α1 and β3 subreceptors are expressed, and the abnormally increased gamma oscillation is reduced.
In general, this study suggests that olfactory-related EEG abnormalities may be a convenient, non-invasive, and low-cost detection indicator that can be used for early clinical investigation of AD.
The study also suggests that GABA signaling pathways are used as targets to enhance GABA.
It can inhibit the synaptic transmission and achieve the AD prevention and treatment strategy to improve the early symptoms of AD, especially the abnormal smell.
Paper summary picture (picture quoted from: Chen et al.
Molecular Neurodegeneration 2021; 16:14) Chen Ming (front row, second from left), Yang Li (front row, middle) (picture source: Yang Li laboratory) Guangzhou University for the article The first completed unit. Ming Chen (current working unit is Anhui Medical University), Yunan Chen (currently a PhD student in the International Max Planck School of Intelligent System Research) and Qingwei Huo (current working unit is Guangzhou University of Chinese Medicine) are the co-first authors of this article .
Professor Yang Li of Guangzhou University is the corresponding author of the article.
The research group of Professor Long Cheng from South China Normal University is a cooperative unit.
The research was funded by the National Natural Science Foundation of China (31771219, 81801064, 81804197, 31871170, 31970915), the major science and technology project of Guangdong Brain Science and Brain-inspired Research (2018B030336001), and the Guangzhou University Hundred Talents Program Startup Fund.
Original link: https://molecularneurodegeneration.
biomedcentral.
com/articles/10.
1186/s13024-021-00434-7 Recommended high-quality scientific research training courses [1] Multi-omics data integration mining and analysis (web) seminar (March 12- 14th, two days and two nights) [2] Patch Clamp and Optogenetics and Calcium Imaging Technology Seminar (February 27-28, 21) (April-May 2020 courses can be booked) [3] Online ︱ Order Symposium on Cell Sequencing Data Analysis and Research Ideas (January 16-17, 21) (can be booked for February-March 2021) [4] Online Course︱ "Scientific Research Image Processing and Mapping" January 23/ 24/26/28 (can be booked for February-March 2021) [5] R language data analysis practical technology (web) seminar (December 26-27, 2020) (can be booked for 2-3, 2020 Monthly course) [6] Data analysis and essay writing training of imaging omics, basic practical training class of MRI brain imaging data processing (imagingology: January 16-17 MRI: January 23-24) (available Book the course from February to March 2020) [7] Thesis illustration, mechanism pattern diagram, scientific research data processing, statistical analysis and chart production and drawing special class (map service provided after class, January 23-24, 30-31 online class ( Available to book courses from February to March 2020) References (swipe up and down to view) [1] Murphy C.
Olfactory and other sensory impairments in Alzheimer disease.
Nat Rev Neurol.
2019; 15: 11–24.
[2] Tan Jie, Luo Minmin.
The processing of olfactory information by the olfactory bulb, Chinese Journal of Biophysics.
2010; 26 (3): 194-208.
[3] Lepousez G, Lledo PM.
Odor discrimination requires proper olfactory fast oscillations in awake mice.
Neuron.
2013; 80: 1010-1024.
【4】Iaccarino HF, Singer AC, Martorell AJ,Rudenko A, Gao F, Gillingham TZ, Mathys H, Seo J, Kritskiy O, Abdurrob F, Adaikkan C, Canter CG.
Rueda R, Emery N.
Brown EN, Boyden ES, Tsai LH.
Gamma frequency entrainment attenuates amyloid load and modifies microglia.
Nature.
2016; 540: 230–235.
[5] Wang D, Clouter A, Chen Q, Kimron L.
Hanslmayr S.
Single-trial phase entrainment of theta oscillations in sensory regions predicts human associative memory performance.
J Neurosci.
2018; 38: 6299-6309.
[6] Nora A.
Herweg, Ethan A.
Solomon, Michael J.
Kahana 1.
Theta oscillations in human memory.
Trends in Cognitive Sciences, 2020; 24: 3.
Plate making︱Wang Sizhen End of this article230–235.
[5] Wang D, Clouter A, Chen Q, Kimron L.
Hanslmayr S.
Single-trial phase entrainment of theta oscillations in sensory regions predicts human associative memory performance.
J Neurosci.
2018; 38: 6299-6309.
[6] Nora A.
Herweg, Ethan A.
Solomon, Michael J.
Kahana 1.
Theta oscillations in human memory.
Trends in Cognitive Sciences, 2020; 24: 3.
Plate making︱Wang Sizhen End of this article230–235.
[5] Wang D, Clouter A, Chen Q, Kimron L.
Hanslmayr S.
Single-trial phase entrainment of theta oscillations in sensory regions predicts human associative memory performance.
J Neurosci.
2018; 38: 6299-6309.
[6] Nora A.
Herweg, Ethan A.
Solomon, Michael J.
Kahana 1.
Theta oscillations in human memory.
Trends in Cognitive Sciences, 2020; 24: 3.
Plate making︱Wang Sizhen End of this article
