{"id":1104,"date":"2023-12-03T13:31:03","date_gmt":"2023-12-03T18:31:03","guid":{"rendered":"https:\/\/students.bowdoin.edu\/bowdoin-science-journal\/?p=1104"},"modified":"2023-12-03T13:31:03","modified_gmt":"2023-12-03T18:31:03","slug":"retrieving-forgotten-memories-with-optogenetics","status":"publish","type":"post","link":"https:\/\/students.bowdoin.edu\/bowdoin-science-journal\/biology\/retrieving-forgotten-memories-with-optogenetics\/","title":{"rendered":"Retrieving Forgotten Memories With Optogenetics"},"content":{"rendered":"

Alzheimer\u2019s disease is a neurodegenerative disorder in which patients experience a progressive decline in memory <\/span>(Roy et. al, 2016)<\/span>. The early stages involve struggles to remember mostly episodic memories, which are memories of personal experiences that are linked to activity in the hippocampus. To discover potential treatments, scientists have tried to better understand the biological mechanisms behind the disease. Optogenetic activation of engram cells and calculation of dendritic spine density are two methods to research the disease. <\/span>Dendritic spines are extensions from dendrites, which are the structures that receive signals from other neurons and pass them to the cell body. Memory is associated with changes in dendritic spines or the formation of new ones, which makes scientists believe that they serve as sites for memory formation and storage (Roy et. al, 2016). Engram cells are biological traces of established memories that store the information and are reactivated when memories are retrieved (Ortega-de San Luis et al., 2022). Optogenetics is a technique in which genes for light sensitive proteins are injected into specific neurons in the brain so that they can be activated by laser lights that open ion channels (Figure 1).\u00a0<\/span><\/p>\n

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Figure 1. The process of optogenetics <\/span>(Adapted from Buchen, 2010).<\/span>\u00a0<\/span><\/p>\n

A 2016 study affiliated with the Massachusetts Institute of Technology used optogenetics to activate engram cells in the hippocampus of mouse models of early Alzheimer\u2019s disease (AD) (Roy et al., 2016). With direct activation of hippocampal cells, the mice were able to retrieve the memories they had forgotten, indicating that the issue is retrieving memories; the memories are still available in the brain, but there is a problem in recalling them. Amnesia in early AD mice is also correlated with a reduction of spine density of engram cells in the hippocampus. The study showed that restoring dendritic spine density with optogenetic activation allows for the retrieval of long-term memory. Spine density was restored as the optogenetic activation allowed sodium ions to flow into the neurons and consequently depolarized them (meaning the cell is less negatively charged). This depolarization triggers long term potentiation, which is the process of strengthening connections between neurons that underlies memory and learning. Thus, restoration of spine density could lead to an effective strategy for treating memory loss in patients with early Alzheimer\u2019s disease.\u00a0<\/span><\/p>\n

In the experiment, the scientists labeled engram cells in the mouse models of Early Alzheimer\u2019s disease and tested memory recall with contextual fear conditioning and long-term memory testing. Contextual fear conditioning is when mice are trained to associate a particular context (a cage) with a shock, creating a memory of the association in the hippocampus. Long-term memory was tested by placing them back into the cage and measuring their freezing behavior, a commonly used measure of fear. They also calculated dendritic spine density.\u00a0<\/span><\/p>\n

The researchers found that optogenetic activation of memory engrams restores fear memory in early AD mice and that reversal of engram-specific spine deficits rescues memory in early AD mice. The diagram below shows the process of fear conditioning (panel t): the mice were trained to associate a shock with a certain context, and then their long term memory was tested by placing them back into the cage and observing their \u201cfreeze response,\u201d which demonstrates that they feel fear in the cage because of the memory of the shock in the cage. The graphs show that when the engrams were activated optogenetically, the mice froze more than they did when the engrams were not activated, indicating that the optogenetic activation of the engram cells restored the mice\u2019s memory of the fearful context.\u00a0<\/span><\/p>\n

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Figure 2. Optogenetic activation of memory engrams restores fear memory in early AD mice (Adapted from Roy et al., 2016, Fig. 1).\u00a0<\/span><\/p>\n

The results of this study provide directions and hope for future treatments for Alzheimer\u2019s Disease. If the amnesia is due to retrieval impairments, memory could be restored by technologies involving brain stimulation, like the optogenetic activation did in the mouse models. However, optogenetics is currently a technique only possible in animals since it is invasive, so further research will have to be done to discover a technique employing the principle in a more plausible way for humans, perhaps by finding a way to restore spine density in engram cells. There are other limitations when it comes to future treatments for Alzheimer\u2019s because of the fact that they studied only early AD mice and episodic memory. Even though they showed that amnesia in early AD mice impairs memory retrieval, long-term memory <\/span>storage<\/span><\/i> in advanced stages of AD may also be impaired and eventually lost as neuronal degeneration progresses. Also, humans with early AD often exhibit non-episodic memory deficits as well, which involve brain structures outside of the medial temporal lobe that the current study did not investigate. However, overall, the findings contribute to a better understanding of memory retrieval deficits in early cases of AD, which may also apply to other neurological diseases in which patients have difficulty with memory retrieval, such as Huntington\u2019s Disease.\u00a0<\/span><\/p>\n

 <\/p>\n

Literature Cited<\/span><\/p>\n

Buchen, L. (2010). Neuroscience: Illuminating the brain. <\/span>Nature<\/span><\/i>, <\/span>465<\/span><\/i>(7294), Article 7294.<\/span> https:\/\/doi.org\/10.1038\/465026a<\/span><\/a><\/p>\n

Ortega-de San Luis, C., & Ryan, T. J. (2022b). Understanding the physical basis of memory: Molecular mechanisms of the engram. <\/span>The Journal of Biological Chemistry<\/span><\/i>, <\/span>298<\/span><\/i>(5), 101866.<\/span> https:\/\/doi.org\/10.1016\/j.jbc.2022.101866<\/span><\/a><\/p>\n

Roy, D. S., Arons, A., Mitchell, T. I., Pignatelli, M., Ryan, T. J., & Tonegawa, S. (2016d). Memory retrieval by activating engram cells in mouse models of early Alzheimer\u2019s disease. <\/span>Nature<\/span><\/i>, <\/span>531<\/span><\/i>(7595), 508\u2013512.<\/span> https:\/\/doi.org\/10.1038\/nature17172<\/span><\/a><\/p>\n

Yuhas, D. (n.d.). <\/span>Forgotten Memories May Remain Intact in the Brain<\/span><\/i>. Scientific American. Retrieved November 4, 2023, from<\/span> https:\/\/www.scientificamerican.com\/article\/forgotten-memories-may-remain-intact-in-the-brain\/<\/span><\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

Alzheimer\u2019s disease is a neurodegenerative disorder in which patients experience a progressive decline in memory (Roy et. al, 2016). The early stages involve struggles to remember mostly episodic memories, which are memories of personal experiences that are linked to activity in the hippocampus. To discover potential treatments, scientists have tried to better understand the biological […]<\/p>\n","protected":false},"author":673,"featured_media":1194,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_genesis_hide_title":false,"_genesis_hide_breadcrumbs":false,"_genesis_hide_singular_image":false,"_genesis_hide_footer_widgets":false,"_genesis_custom_body_class":"","_genesis_custom_post_class":"","_genesis_layout":"","footnotes":""},"categories":[63,68],"tags":[132,133],"class_list":{"0":"post-1104","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-biology","8":"category-psych-neuro","9":"tag-memory","10":"tag-optogenetics","11":"entry"},"featured_image_src":"https:\/\/students.bowdoin.edu\/bowdoin-science-journal\/wp-content\/uploads\/sites\/35\/2023\/12\/Screenshot-2023-12-03-at-1.21.34\u202fPM-600x400.png","featured_image_src_square":"https:\/\/students.bowdoin.edu\/bowdoin-science-journal\/wp-content\/uploads\/sites\/35\/2023\/12\/Screenshot-2023-12-03-at-1.21.34\u202fPM-600x600.png","author_info":{"display_name":"Hailey Ryan '26","author_link":"https:\/\/students.bowdoin.edu\/bowdoin-science-journal\/author\/hryan2\/"},"_links":{"self":[{"href":"https:\/\/students.bowdoin.edu\/bowdoin-science-journal\/wp-json\/wp\/v2\/posts\/1104","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/students.bowdoin.edu\/bowdoin-science-journal\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/students.bowdoin.edu\/bowdoin-science-journal\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/students.bowdoin.edu\/bowdoin-science-journal\/wp-json\/wp\/v2\/users\/673"}],"replies":[{"embeddable":true,"href":"https:\/\/students.bowdoin.edu\/bowdoin-science-journal\/wp-json\/wp\/v2\/comments?post=1104"}],"version-history":[{"count":0,"href":"https:\/\/students.bowdoin.edu\/bowdoin-science-journal\/wp-json\/wp\/v2\/posts\/1104\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/students.bowdoin.edu\/bowdoin-science-journal\/wp-json\/wp\/v2\/media\/1194"}],"wp:attachment":[{"href":"https:\/\/students.bowdoin.edu\/bowdoin-science-journal\/wp-json\/wp\/v2\/media?parent=1104"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/students.bowdoin.edu\/bowdoin-science-journal\/wp-json\/wp\/v2\/categories?post=1104"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/students.bowdoin.edu\/bowdoin-science-journal\/wp-json\/wp\/v2\/tags?post=1104"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}