Release date: 2018-05-22
In ancient Greek mythology, there is a goddess named Mnemosyune, one of the twelve Titans, who is in charge of memory. This goddess has nine beautiful daughters, specializing in literature and science, and also the muse who we often refer to now. The ancient Greeks regarded memory as the mother of literature and science. Without memory, there would be no literature and science.
At the same time, the ancient Greeks were also puzzled by "can remember things." How does memory come about? The philosopher Plato thinks this way: the way the brain impresses things should be the same as the sharp objects leaving scratches on the wax plate. Once the impression is formed, it will always exist until it is smoothed; after being smoothed, The new smooth surface that appears is the opposite of memory, which is completely forgotten.
This passage is thousands of years away from the discovery of modern neuroscience, but it is not far from it. There is indeed a "wax version" in our brain, or more like a blackboard used by the teacher for lectures. The new memory that is known from the outside world is like a teacher's blackboard, recorded on the blackboard. To convert these memories into long-lasting memories, we need to extract the blackboard from the blackboard to the notebook. Naturally, the "blackboard" in the brain is also the same as the real blackboard. It is limited in size. When it is full, it is necessary to erase the old ones to make room for new ones.
This blackboard is called the hippocampus. The blackboard is the connection of the neuron's synapses. What erases everything is the intoxicating black sweet town - sleep.
When awake, the connections between brain synapses are often enhanced, which requires negative regulation during sleep, but the specific effects of sleep on synaptic plasticity are unclear. Recently, a study published in the top journal Science has uncovered the mysterious relationship between sleep and memory.
Yuji Ikegaya from the University of Tokyo in Japan and Shigeyoshi Fujisawa from the RIKEN Institute of Brain Science found that in the main state of sleep and slow wave, a kind of sharp wave (sharp) The special brainwaves of -wave ripples, SWR) are the key to synaptic negative regulation [1]. Specific silent spikes prevent the spontaneous downregulation of synapses and hinder the learning of new memories!
Ikeya Yuji
Fujisawa Maoyi
In the long history of mankind, many civilizations have survived and developed, relying on the memory of the brain, and the mechanism of generation and preservation of memory is also a key issue in neuroscience. As early as 1971, the first related study appeared. The researchers found in the hippocampus of mice that when new memory is formed, hippocampal neurons form a transient, stable connection [2]. As a result, hippocampus has become one of the brain regions that have attracted the attention of researchers.
The hippocampus has been shown to be associated with many important brain functions such as memory and emotions, especially memory, including spatial memory, learning and memory, and episodic memory. Taking spatial memory as an example, without the aid of the hippocampus, it is difficult for us to remember the relative position of the object, then everyone will become a road fool. However, the size of the hippocampus is limited. We cannot store an infinite number of numbers in a limited space, right?
There have been enough research results to show that the hippocampus is not a memory of memory, it is only the birthplace of new memories, after which new memories will be transferred to the new cortex to form long-lasting memories, while the hippocampus is "formatted". Welcome to the next new memory. Studies in animals [3] and humans [4] have shown that sleep plays a crucial role in this resetting process.
Wipe off old memories and write new memories
When the sleep is getting deeper, the brain waves show synchronized slow waves, and then we enter slow-wave sleep. In this state, the hippocampus spontaneously releases instantaneous high-frequency oscillations, and the researchers call this special brainwave a sharp wave (SWR). Sharp waves are associated with activation of new memory neurons [5] and are also involved in the integration of memory [6]. But so far, no studies have been done to link spikes and synaptic plasticity.
In order to understand the relationship between the two, Professor Ikegu and Professor Fujisawa conducted an experiment. The researchers attempted to silence the sharp waves using optogenetic methods and see if this would have an impact on the formation of new memories.
The researchers first exposed the mice to an unfamiliar environment, as previous studies have confirmed that after spatial learning, the hippocampus produces more spikes [7]. Sure enough, the frequency of spikes produced by mice has nearly doubled. Subsequently, the researchers used optogenetics to silence related neurons. This causes 97.7 ± 1.8% of the spikes to be suppressed.
The researchers examined synapses in the brain of mice and found a strange phenomenon. In normal mice, synaptic connections have decreased after experiencing spikes, but the synapses in mice that have silenced the spikes have changed little! Does this mean that the hippocampus' "reset" process has been hampered? Does this affect the formation of new memories in mice?
SWR silenced mouse (red) synaptic plasticity is blocked
The researchers then tested the spatial learning ability of mice. The researchers asked the mice to briefly touch a new environment and secretly change the layout of the scene before putting the mice back. Sure enough, the mice that were silenced by the sharp waves were obviously not remembering the layout of the new environment, and the learning and memory ability was lower than that of normal mice!
This shows that the sharp wave frequency is the key to the synaptic plasticity reset process, and losing it will seriously affect the formation of new memories!
"I can't sleep well, I want to be stupid, I don't want to bully."
Researchers have tried to find out the mechanism behind the sharp wave frequency affecting synaptic plasticity. According to previous studies, the size and intensity of synapses are related to glutamate receptor (NMDAR)-mediated regulation mechanisms [8], so the researchers first attempted to use NMDAR antagonists in mouse hippocampal brain slices.
Under normal circumstances, the spikes produced by the hippocampus will gradually decrease over time. When NMDAR antagonists were administered, the reduction in spikes was prevented. This also suggests that the lowering response of spikes is the spontaneous change in synaptic plasticity, not the aging of the sliced ​​tissue or the fatigue of the synapse.
Subsequently, the researchers conducted experiments in mice. After exposure to a new environment, mice were given NMDAR antagonist MK801 or saline, respectively, and changes in synapses in the brain were examined. Synaptic changes in mice receiving saline injection were normal, connections associated with old memory were cleared, and new memory-related connections were increased; mice injected with MK801 were less fortunate, and their synaptic plasticity activities were completely Suppressed! It can be seen that the role of spikes is dependent on the function of NMDA receptors.
Synaptic plasticity in mice antagonizing NMDAR is impaired
This is the answer to "Why do we need to sleep?" In the process of constant memory, the hippocampus repeats the cycle of "writing" - "erasing", and sleep plays a key role in the latter. Sleeping badly, this is really not your illusion.
In more diseases, such as autism and schizophrenia, the occurrence of spikes during sleep is also subject to certain disturbances, and the cranial nerve circuit shows higher excitability. The investigators are conducting further investigations based on the results of this study in an attempt to find a link between the level of spike sputum and certain autistic symptoms (stubborn, lack of social, etc.) and schizophrenic symptoms (谵妄, victim delusions, etc.). And the possibility of recovering these symptoms from a sharp sputum angle [9].
Reference material
[ 1 ] http://science.sciencemag.org/content/359/6383/1524
[ 2 ] J. O ' Keefe, J. Dostrovsky , Brain Res. 34 , 171 ( 1971 ) .
[3] AK Lee, MA Wilson, Neuron 36, 1183 ( 2002 ) .
[4] L. Marshall et al., Nature 444, 610 ( 2006 ) .
[5] AK Lee, MA Wilson, Neuron 36, 1183 – 1194 ( 2002 ) .
[6] V. Ego-Stengel, MA Wilson, Hippocampus 20, 1 – 10 ( 2010 ) .
[ 7 ] O. Eschenko, W. Ramadan, M. M ö lle, J. Born, SJ Sara, Learn.
Mem. 15, 222 – 228 ( 2008 ) .
[8] Q. Zhou, KJ Homma, MM Poo, Neuron 44, 749 – 757 ( 2004 ) .
[ 9 ] https://news.mynavi.jp/article/20180216-585504/
[ 10 ] http://science.sciencemag.org/content/359/6383/1461
Source: Singularity Network
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