This week we investigated two article written by Steve Ramirez, a PI at Boston Universities Center for Memory & Brain. His two articles focus on using optogenetics as an intervention in two memory paradigms. The first article published in 2013 is titles "Creating a False Memory in the Hippocampus". The basis for this experiment was proving that mice were able to falsely encode a memory and identifying the cells and circuits involved in this process. By using ontogenetic manipulation Ramirez and his team were able to create a false memory by stimulating select cells in the dente gyrus (DG) of the hippocampus in mice. The mice were first allowed to familiarize themselves with place "A" while cells in the DG or CA1 were labeled with ChR2-mCherry. Mice were then fear conditioned by pairing an electric foot shock with simultaneous pulses of light in place "B", optically reactivating the cells labeled in place A. When the mice were returned to place A the expressed fear conditioned freezing behavior similar to when reintroduced to place B, however they did not exhibit increase in freezing behavior compared to baseline when placed in novel place "C". Ramirez and his team went on further to distinguish the DG from CA1 cells in their involvement in encoding false memories and even show that false memories can be induced. The findings from this study shed light in the dynamic interaction between false and genuine memories as well as the specific cells involved in these processes.
Ramirez and his team's second article is entitled "Activating positive memory engrams suppresses press ion-like behavior". This article is jarringly different from several of our previous studies. Previous articles focused on inducing depressive behaviors. This article explores optogenetics as an intervention for acute rescue of depressive-like behaviors by targeting specific glutamanergice cells i the hippocampus-amygdala-nucleus accumbent pathway. By activating cells associated with a positive memory engram the team was able to reverse depressive behaviors associated with anhedonia and motivation (sucrose preference test and tail-suspension test). These methods were less effective for anxiety related behaviors such as those associate with an open-file test and elevated plus maze test. This touches on a topic we have discussed at lengths during class. Animal models are able to produce quantifiable behavioral measures as representations of anxiety and depression, however they are limited in their specificity and clinical application. The overlap of symptoms of anxiety and depression blur the lines for treatment in human subjects and specificity of animal models. While this experiment, like many others, was not necessarily applicable to both anxiety and depression, it did suggest a new route for fast acting anti-depressant treatment. The activation of cells associated with positive memories acted as quickly as some of the less conventional anti-depressant methods such as deep-brain stimulation and ketamine. Due to the slow acting effects of typical AD medications such as SSRIs, it is vital we continue to explore new methods of treating these psychiatric disorders with more immediate and for effective responses.
Ramirez and his team's second article is entitled "Activating positive memory engrams suppresses press ion-like behavior". This article is jarringly different from several of our previous studies. Previous articles focused on inducing depressive behaviors. This article explores optogenetics as an intervention for acute rescue of depressive-like behaviors by targeting specific glutamanergice cells i the hippocampus-amygdala-nucleus accumbent pathway. By activating cells associated with a positive memory engram the team was able to reverse depressive behaviors associated with anhedonia and motivation (sucrose preference test and tail-suspension test). These methods were less effective for anxiety related behaviors such as those associate with an open-file test and elevated plus maze test. This touches on a topic we have discussed at lengths during class. Animal models are able to produce quantifiable behavioral measures as representations of anxiety and depression, however they are limited in their specificity and clinical application. The overlap of symptoms of anxiety and depression blur the lines for treatment in human subjects and specificity of animal models. While this experiment, like many others, was not necessarily applicable to both anxiety and depression, it did suggest a new route for fast acting anti-depressant treatment. The activation of cells associated with positive memories acted as quickly as some of the less conventional anti-depressant methods such as deep-brain stimulation and ketamine. Due to the slow acting effects of typical AD medications such as SSRIs, it is vital we continue to explore new methods of treating these psychiatric disorders with more immediate and for effective responses.
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