Both papers are from the same lab and are about optogenetically stimulating memory engrams to produce an artificial response. The 2013 paper focused on fear conditioning and memory. The 2015 focused on depressive-like behaviors. Both papers used similar materials in their experiments. They injected c-fos-tTA mice with TRE-ChR2-mCherry and used doxycycline to control the expression of ChR2 and used ChR2 to label the neurons activated in particular contexts.
In the 2013 paper, the researchers stimulated memory engrams to create fear behavior in contexts in which animals were not fear conditioned. This showed that stimulation of engrams can be used to apply memories in not previously associated contexts. In the 2015 paper, researchers built upon the 2013 research and stimulated positive memory engrams to ameliorate depressive-like behaviors. This showed that stimulation of specifically positive memory engrams can be used to rescue animals from depression-related symptoms. However, these effects were restricted to escape-related behavior and sucrose preference test and were not seen in the performance on open-field test or elevated plus maze test. During our Week 2 discussion, it came up that the Santarelli et al. (2003) paper only used measures of anxiety-related behavior and generalized this to make conclusions about the depression model and the results of this paper support that anxiety-like behaviors can not be used to sufficiently represent the model of depression.
What I found particularly interesting in the 2015 paper is the experiment they conducted to investigate potential long-term effects of chronic reactivation of positive memory engrams. They showed that 5-day stimulation of positive memory engrams produced increased struggling and sucrose preference in mice even after optical stimulation and this group of mice showed increased neurogenesis. From the Week 2 papers, we know that neurogenesis is related to antidepressant behavioral effects. The search for long-term alieviation from depressive-related behaviors is much more applicable to research for a solution for depression in humans since the goal is not to pause depression for minutes the way researchers do so in rodents but to find a solution that will have longer-term effects.
What is a memory? The 2013 paper is titled “Creating a False Memory in the Hippocampus” which is very provocative but potentially misleading. Can what they have done in the mice be considered “creating a memory”? Is it an actually memory in that the mice are remembering the experience of being fear-conditioned and reacting to this memory? Or is it really more of an association such that the stimulation of the memory engram inhibits the neurons involved in movement and the mice don’t actually remember anything? Is there a difference between remembering and the memory engram being activated? Does stimulation of the memory engram necessarily cause remembering in the way that humans think about remembering? Could we ever know?
The 2013 used multiple distinct contexts but I wonder how different they were and if this could impact how mice react when being stimulated. Could the context for fear-conditioning and the neutral context could be so different that the stimulation of the fear-condition engram causes confusion, almost like cognitive dissonance?
Is deja vu a restimulation of a memory engram?
In the 2013 paper, the researchers stimulated memory engrams to create fear behavior in contexts in which animals were not fear conditioned. This showed that stimulation of engrams can be used to apply memories in not previously associated contexts. In the 2015 paper, researchers built upon the 2013 research and stimulated positive memory engrams to ameliorate depressive-like behaviors. This showed that stimulation of specifically positive memory engrams can be used to rescue animals from depression-related symptoms. However, these effects were restricted to escape-related behavior and sucrose preference test and were not seen in the performance on open-field test or elevated plus maze test. During our Week 2 discussion, it came up that the Santarelli et al. (2003) paper only used measures of anxiety-related behavior and generalized this to make conclusions about the depression model and the results of this paper support that anxiety-like behaviors can not be used to sufficiently represent the model of depression.
What I found particularly interesting in the 2015 paper is the experiment they conducted to investigate potential long-term effects of chronic reactivation of positive memory engrams. They showed that 5-day stimulation of positive memory engrams produced increased struggling and sucrose preference in mice even after optical stimulation and this group of mice showed increased neurogenesis. From the Week 2 papers, we know that neurogenesis is related to antidepressant behavioral effects. The search for long-term alieviation from depressive-related behaviors is much more applicable to research for a solution for depression in humans since the goal is not to pause depression for minutes the way researchers do so in rodents but to find a solution that will have longer-term effects.
What is a memory? The 2013 paper is titled “Creating a False Memory in the Hippocampus” which is very provocative but potentially misleading. Can what they have done in the mice be considered “creating a memory”? Is it an actually memory in that the mice are remembering the experience of being fear-conditioned and reacting to this memory? Or is it really more of an association such that the stimulation of the memory engram inhibits the neurons involved in movement and the mice don’t actually remember anything? Is there a difference between remembering and the memory engram being activated? Does stimulation of the memory engram necessarily cause remembering in the way that humans think about remembering? Could we ever know?
The 2013 used multiple distinct contexts but I wonder how different they were and if this could impact how mice react when being stimulated. Could the context for fear-conditioning and the neutral context could be so different that the stimulation of the fear-condition engram causes confusion, almost like cognitive dissonance?
Is deja vu a restimulation of a memory engram?
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