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The increase of calcium ions in hippocampal astrocytes induces the co-release of D-serine and glutamate through Best1
.
The release of glutamate from CA3 neurons can induce local norepinephrine release by activating presynaptic AMPAR at the LC terminal
Source: Institute of Basic Science
"The measure of intelligence is the ability to change
.
"-Albert Einstein
Since we live in a dynamically changing environment, it is important that our brain not only learn new things, but also modify existing memories
.
This is often referred to as "cognitive flexibility"
Researchers from the Center for Cognition and Society at the Daejeon Institute of Basic Science (IBS) in South Korea, under the leadership of C.
Justin LEE, reported that astrocytes in the brain regulate cognitive flexibility
.
Specifically, they found that the ability of astrocytes to simultaneously regulate and integrate nearby synaptic plasticity is important for promoting cognitive flexibility
It is believed that in the early stages of autism, schizophrenia and Alzheimer’s disease, the lower cognitive flexibility of patients with brain disorders is due to the function of N-methyl-D-aspartate receptors (NMDARs) Caused by reduction
.
Although NMDARs are important receptors for synaptic plasticity and are activated by many agonists and co-agonists, the source of one of the co-agonists, D-serine, has been controversial
In particular, the researchers found that long-term inhibition of heterosynapses (LTD) is a phenomenon mediated by astrocytes.
When nearby synapses become active, inactive synapses become weaker, which is very important for cognition.
Flexibility is essential
.
"Since each astrocyte is in contact with more than 100,000 synapses, astrocytes can control multiple synapses and integrate synaptic plasticity at the same time," said KOH Wuhyun, the first author of the study
.
In this report, they studied the Best1 knockout (Best1KO) mouse model that lacks heterosynaptic LTD due to reduced NMDARs
.
In the Morris water maze experiment, mice tried to find a hidden platform.
Interestingly, after injection of D-serine at the early stage of learning to improve the tension of NMDARs in Best1 KO mice, the memory modification problem was restored in subsequent experiments
.
This finding shows that memory flexibility is determined by the initial learning time, which is different from the previous theory that synaptic plasticity occurs only when memory modification is required
In addition, the researchers found that norepinephrine and its receptor α1-AR can activate astrocytes and cause the co-release of D-serine and glutamate
.
This means that the flexibility of memory can be determined by the degree of concentration and arousal during learning
C.
Justin LEE said: "Previous research mainly focused on the changes in specific synapses to stimuli
.
During the learning process, a change in one synapse will cause changes in nearby synapses.
The discovery of this phenomenon indicates that it is necessary to find out What happens at other synapses is important for understanding the mechanisms by which learning and memory are formed
.
It is hoped that this research will provide valuable insights on how to reduce or treat the symptoms of autism, schizophrenia, and early dementia, which are believed to be Decrease cognitive flexibility
.
"
Magazine
Biological Psychiatry
DOI
10.
1016/j.
biopsych.
2021.
10.
012
Methodological research
Experimental Study
Subject of research
animal
Article title
Astrocytes render memory flexible by releasing D-serine and regulating NMDAR tone in the hippocampus
