{"id":69,"date":"2021-12-12T22:42:52","date_gmt":"2021-12-12T22:42:52","guid":{"rendered":"https:\/\/experimentalfrontiers.peachpuff-wolverine-566518.hostingersite.com\/?p=69"},"modified":"2021-12-13T13:02:23","modified_gmt":"2021-12-13T13:02:23","slug":"where-is-memory-stored","status":"publish","type":"post","link":"https:\/\/scienceblog.com\/experimentalfrontiers\/2021\/12\/12\/where-is-memory-stored\/","title":{"rendered":"Where is memory stored?"},"content":{"rendered":"<p>Learning is a function of the brain. Memory is stored in synapses, the connections between neurons. They become stronger each time a connection takes place. \u201cNeurons that fire together, wire together.\u201d<\/p>\n<p>This theory was put forward by\u00a0<a href=\"https:\/\/www.google.com\/books\/edition\/The_Organization_of_Behavior\/ddB4AgAAQBAJ\" target=\"_blank\" rel=\"noopener\">Donald Hebb in 1949<\/a>, and it is, at best,\u00a0<a href=\"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnsys.2018.00052\/full#B64\" target=\"_blank\" rel=\"noopener\">one small part<\/a>\u00a0of the story.\u00a0<a href=\"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnsys.2016.00088\/full\" target=\"_blank\" rel=\"noopener\">It may be completely false<\/a>. I will briefly reference 6 counterexamples to the neuronal theory of memory, then suggest ideas how we might prospect for a new theory of memory.<\/p>\n<p><strong>Six and a half counterexamples<\/strong><\/p>\n<ol>\n<li>Microbes can learn. Learning in paramecia was first noted\u00a0<a href=\"https:\/\/psycnet.apa.org\/record\/1926-01078-001\" target=\"_blank\" rel=\"noopener\">in 1911<\/a>. After they have been put in a narrow capillary, they find their way out\u00a0<a href=\"https:\/\/psycnet.apa.org\/record\/1940-04479-001\" target=\"_blank\" rel=\"noopener\">faster if they had been there before<\/a>. They learn to avoid an electric shock with\u00a0<a href=\"https:\/\/elifesciences.org\/articles\/61907\" target=\"_blank\" rel=\"noopener\">classical Pavlovian conditioning<\/a>, and if they are trained on a platinum wire that has food plaited to it, they will subsequently approach an unplaited wire [<a href=\"https:\/\/doi.apa.org\/doiLanding?doi=10.1037%2Fh0063093\" target=\"_blank\" rel=\"noopener\">Gelber, 1952]<\/a>.\n<div style='position:relative;padding-bottom: calc(56.25% + 44px)'><iframe title=\"Amoeba hunts and kills paramecia and stentor... to music by Lamar; Genesis; Winter; Zimmer\" src='https:\/\/gfycat.com\/ifr\/marvelousoilycaribou' frameborder='0' scrolling='no' width='100%' height='100%' style='position:absolute;top:0;left:0;' allowfullscreen><\/iframe><\/div>\n<\/li>\n<li>Planaria are flatworms, about a centimeter long, with unlimited regenerative potential. You can cut off a head, and it grows a new tail, or cut off a tail and it grows a new head. Planaria can also be trained to respond to a Pavlovian stimulus. If you do this and then cut off the worm\u2019s tail, then the tail-half that grows a new head remembers the training, though not as well as the head-half that grows a new tail.\u00a0<a href=\"https:\/\/psycnet.apa.org\/record\/1962-00603-001\" target=\"_blank\" rel=\"noopener\">[Original ref = McConnell 1959<\/a>;\u00a0<a href=\"https:\/\/journals.biologists.com\/jeb\/article-abstract\/216\/20\/3799\/11714\" target=\"_blank\" rel=\"noopener\">Replication by Michael Levin\u2019s lab, 2013<\/a>]<\/li>\n<li>Caterpillars\/butterflies are arthropods, with more advanced nervous systems than worms. Caterpillars can be trained to prefer or to avoid some previously neutral scent.\u00a0<span style=\"color: #373737\">Caterpillars liquefy their brains in the chrysalis on the way to becoming a butterfly, yet the caterpillar\u2019s memories are retained in the butterfly.\u00a0 [<\/span><a href=\"https:\/\/journals.plos.org\/plosone\/article?id=10.1371\/journal.pone.0001736\" target=\"_blank\" rel=\"noopener\">Blackiston, 2008<\/a>]<\/li>\n<li><span style=\"color: #373737\">Millions of monarch butterflies spend the winter clinging to a particular tree in Pacific Grove, CA. In the spring, they fly off in a diaspora, ranging as far as Canada. But six or seven generations later, the summer is over, and the great great grandchildren of the diaspora turn around and find the same tree where the journey started. Somehow, memory is accumulated and passed through six generations of offspring. <img decoding=\"async\" src=\"http:\/\/ww2.kqed.org\/science\/wp-content\/uploads\/sites\/35\/2014\/01\/800px-Monarch-butterflies-pacific-grove-e1389906984424.jpg\" alt=\"Overwintering monarch butterflies return year after year to California groves. Photo taken in Pacific Grove, CA by agunther\" \/><\/span><\/li>\n<li>Heart transplant patients sometimes experience the emotions and even the interests and habits of the heart donor. [<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/31739081\/\" target=\"_blank\" rel=\"noopener\">Liester, 2020<\/a>]<\/li>\n<li>Monica Gagliano is responsible for a new science of plant sociology. Plants communicate with one another, they learn and they remember.\u00a0<a href=\"https:\/\/www.google.com\/books\/edition\/Thus_Spoke_the_Plant\/DcFMDwAAQBAJ\" target=\"_blank\" rel=\"noopener\">Here is her book<\/a>. Needless to say, plants have no brains, and nothing like a neuron.<br \/>\n<img loading=\"lazy\" decoding=\"async\" class=\" wp-image-70 aligncenter\" src=\"https:\/\/scienceblog.com\/wp-content\/uploads\/sites\/7\/2021\/12\/ThusSpokethePlant-300x156.png\" alt=\"\" width=\"465\" height=\"242\" srcset=\"https:\/\/scienceblog.com\/experimentalfrontiers\/wp-content\/uploads\/sites\/7\/2021\/12\/ThusSpokethePlant-300x156.png 300w, https:\/\/scienceblog.com\/experimentalfrontiers\/wp-content\/uploads\/sites\/7\/2021\/12\/ThusSpokethePlant-1024x534.png 1024w, https:\/\/scienceblog.com\/experimentalfrontiers\/wp-content\/uploads\/sites\/7\/2021\/12\/ThusSpokethePlant-768x400.png 768w, https:\/\/scienceblog.com\/experimentalfrontiers\/wp-content\/uploads\/sites\/7\/2021\/12\/ThusSpokethePlant.png 1142w\" sizes=\"auto, (max-width: 465px) 100vw, 465px\" \/><\/li>\n<li>?? There is literature suggesting that memory is transferable by ingestion. Brains of trained rodents are ground up and injected (or fed)\u00a0 into naive rodents who pick up their conditioned responses. This, if replicated, would establish the basis for specific memories storied chemically. But a few prominent references from the 1960s [<a href=\"https:\/\/sci-hub.se\/https:\/\/www.nature.com\/articles\/214453a0\" target=\"_blank\" rel=\"noopener\">Ungar, 1967<\/a>] led to skeptical rebuttal. The validity of these experiments is\u00a0<a href=\"https:\/\/sci-hub.se\/https:\/\/www.tandfonline.com\/doi\/abs\/10.1080\/09647049709525701\" target=\"_blank\" rel=\"noopener\">considered doubtful\u00a0<\/a>today, but anomalies remain.<\/li>\n<\/ol>\n<p>There is also evidence from out of body experiences, near-death experiences, mediumship, precognition, and telepathy. The credible evidence for such effects is overwhelming, but I\u2019m not going to say more about them here because they almost certainly require an explanation outside known physics. It may be that the six examples above also require new physics, but let\u2019s start by looking for new biology within the confines of conventional physics, and look for new physics only if that effort fails.<\/p>\n<p><strong>What are the possibilities for storing information outside the brain?<\/strong><\/p>\n<ul>\n<li>Epigenetics \u2014 markers on DNA (or associated histones) that control gene expression patterns. I think of this as a long shot because it\u2019s hard to imagine how the combination of proteins expressed could code for, say, a map of the return route to California. But epigenetic memory is the only known, documented means by which acquired information is passed from parent to offspring.<\/li>\n<li>Intercellular patterns of electrical potential, as Michael Levin\u2019s lab has been documenting for 20 years. [<a href=\"https:\/\/www.youtube.com\/watch?v=HKWyB9qLP_s\" target=\"_blank\" rel=\"noopener\">VIdeo<\/a>,\u00a0<a href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0958166917302690?casa_token=r6F5L9LQDiQAAAAA:exMF908WyciAmzfIBSf-gPD7YzoEQtldtRsI6R7eUJCUQhhHj7IwKVSBs5nHuianjmlnDk5Iog\" target=\"_blank\" rel=\"noopener\">review article<\/a>]<\/li>\n<li>Intracellular patterns of electric potential. (Distinct from what Levin studies which are patterns across groups of cells.)<\/li>\n<li>Physical structures within a cell, for example the shape of the\u00a0<a href=\"https:\/\/www.genome.gov\/genetics-glossary\/Endoplasmic-Reticulum-Smooth\" target=\"_blank\" rel=\"noopener\">endoplasmic reticulum<\/a>, which functions as a highway for proteins transported within a cell. Membrane structures within a cell. There is no direct evidence for this hypothesis, but\u00a0<a href=\"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2020.00048\/full\" target=\"_blank\" rel=\"noopener\">degradation of the ER is associated with Alzheimer\u2019s dementia<\/a>.<\/li>\n<li>Voltage-gated ion channels that constantly pass positive ions (Na+,K+,Ca++,Mg++) in and out of a cell.<\/li>\n<\/ul>\n<p>Each of these suggests a program for deciding if we\u2019re on the right track. Actually decoding the language of memory is a formidable challenge. But perhaps we can disrupt these systems, one-at-a-time, to see if memory is thereby disrupted, and narrow the search thereby to some candidate vehicle for memory.<\/p>\n<p>The simplest case is for single-celled organisms, so perhaps the inquiry can begin with repeating experiments in paramecia. Try interfering with these candidate mechanisms to see if they affect the degree to which memory is recorded.<\/p>\n<h6><span style=\"color: #212121\"><strong>Molecules\/pathways known to be involved in learning and memory, with homologues in ciliates.<\/strong><\/span><\/h6>\n<div>\n<table>\n<tbody>\n<tr>\n<td><span style=\"color: #212121\"><strong>Molecules\/pathways known to be involved in learning\/memory\u00a0<\/strong><\/span><\/td>\n<td><span style=\"color: #212121\"><strong>Ciliates with reported homologues\u00a0<\/strong><\/span><\/td>\n<td><span style=\"color: #212121\"><strong>References<\/strong><\/span><\/td>\n<\/tr>\n<tr>\n<td><span style=\"color: #212121\">N-methyl-D-aspartate receptor (NMDAR)\u00a0<\/span><\/td>\n<td><span style=\"color: #212121\"><em>P. primaurelia<\/em><\/span><span style=\"color: #212121\">\u00a0(only partial sequences)\u00a0<\/span><\/td>\n<td><a href=\"https:\/\/elifesciences.org\/articles\/61907#bib80\" target=\"_blank\" rel=\"noopener\"><span style=\"color: #212121\">Ramoino et al., 2014<\/span><\/a><\/td>\n<\/tr>\n<tr>\n<td><span style=\"color: #212121\">Glutamate receptor\u00a0<\/span><\/td>\n<td><span style=\"color: #212121\"><em>P. tetraurelia<\/em><\/span><\/td>\n<td><a href=\"https:\/\/elifesciences.org\/articles\/61907#bib104\" target=\"_blank\" rel=\"noopener\"><span style=\"color: #212121\">Van Houten et al., 2000<\/span><\/a><\/td>\n<\/tr>\n<tr>\n<td><span style=\"color: #212121\">Calmodulin<\/span><\/td>\n<td><span style=\"color: #212121\"><em>P. tetraurelia<\/em><\/span><\/td>\n<td><a href=\"https:\/\/elifesciences.org\/articles\/61907#bib77\" target=\"_blank\" rel=\"noopener\"><span style=\"color: #212121\">Plattner and Verkhratsky, 2018<\/span><\/a><\/td>\n<\/tr>\n<tr>\n<td><span style=\"color: #212121\">cAMP<\/span><\/td>\n<td><span style=\"color: #212121\"><em>P. tetraurelia<\/em><\/span><\/td>\n<td><a href=\"https:\/\/elifesciences.org\/articles\/61907#bib77\" target=\"_blank\" rel=\"noopener\"><span style=\"color: #212121\">Plattner and Verkhratsky, 2018<\/span><\/a><\/td>\n<\/tr>\n<tr>\n<td><span style=\"color: #212121\">cAMP-dependent protein kinase<\/span><\/td>\n<td><span style=\"color: #212121\"><em>P. tetraurelia<\/em><\/span><\/td>\n<td><a href=\"https:\/\/elifesciences.org\/articles\/61907#bib77\" target=\"_blank\" rel=\"noopener\"><span style=\"color: #212121\">Plattner and Verkhratsky, 2018<\/span><\/a><\/td>\n<\/tr>\n<tr>\n<td><span style=\"color: #212121\">Mitogen activated protein kinase (MAPK)\u00a0<\/span><\/td>\n<td><span style=\"color: #212121\"><em>P. caudatum<\/em><\/span><\/td>\n<td><a href=\"https:\/\/elifesciences.org\/articles\/61907#bib107\" target=\"_blank\" rel=\"noopener\"><span style=\"color: #212121\">Wada and Watanabe, 2007<\/span><\/a><\/td>\n<\/tr>\n<tr>\n<td><span style=\"color: #212121\">Protein kinase C (PKC)\u00a0<\/span><\/td>\n<td><span style=\"color: #212121\"><em>T. thermophilia<\/em><\/span><\/td>\n<td><a href=\"https:\/\/elifesciences.org\/articles\/61907#bib45\" target=\"_blank\" rel=\"noopener\"><span style=\"color: #212121\">Hegyesi and Csaba, 1994<\/span><\/a><\/td>\n<\/tr>\n<tr>\n<td><span style=\"color: #212121\">Calcineurin<\/span><\/td>\n<td><span style=\"color: #212121\"><em>P. tetraurelia<\/em><\/span><\/td>\n<td><a href=\"https:\/\/elifesciences.org\/articles\/61907#bib77\" target=\"_blank\" rel=\"noopener\"><span style=\"color: #212121\">Plattner and Verkhratsky, 2018<\/span><\/a><\/td>\n<\/tr>\n<tr>\n<td><span style=\"color: #212121\">DNA methyltransferases (DNMTs)<\/span><\/td>\n<td><span style=\"color: #212121\"><em>T. thermophilia<\/em><\/span><\/td>\n<td><a href=\"https:\/\/elifesciences.org\/articles\/61907#bib44\" target=\"_blank\" rel=\"noopener\"><span style=\"color: #212121\">Guti\u00e9rrez et al., 2000<\/span><\/a><\/td>\n<\/tr>\n<tr>\n<td><span style=\"color: #212121\">Histone acetyltransferases (HATs)<\/span><\/td>\n<td><span style=\"color: #212121\"><em>T. thermophilia<\/em><\/span><\/td>\n<td><a href=\"https:\/\/elifesciences.org\/articles\/61907#bib105\" target=\"_blank\" rel=\"noopener\"><span style=\"color: #212121\">Vavra et al., 1982<\/span><\/a><\/td>\n<\/tr>\n<tr>\n<td><span style=\"color: #212121\">Histone deacetylases (HADCs)<\/span><\/td>\n<td><span style=\"color: #212121\"><em>T. thermophilia<\/em><\/span><\/td>\n<td><a href=\"https:\/\/elifesciences.org\/articles\/61907#bib109\" target=\"_blank\" rel=\"noopener\"><span style=\"color: #212121\">Wiley et al., 2005<\/span><\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<\/div>\n<p><a href=\"https:\/\/elifesciences.org\/articles\/61907\" target=\"_blank\" rel=\"noopener\">source: Gershman et al<\/a><\/p>\n<p>Epigenetics \u2014 Methyl transferases could enhance memory storage, if the epigenetic hypothesis is correct. If inhibition of methyl transferases prevents memory storage, that would point toward epigenetic memory. There are, however, too many epigenetic mechanisms independent of methylation for this experiment to be dispositive.<\/p>\n<p>Gated ion channels can be manipulated with drugs and with certain frequencies of radio waves.<\/p>\n<p>If physical structures within the cell are the seat of memory, the best way to study this might be to apply AI algorithms to photographs of cells that store different memories, before and after these memories are recorded. This is virgin territory, AFAIK.<\/p>\n<p>Levin has found planaria to be his most productive model organism. They readily learn and they have extraordinary power of regeneration. Where is the memory stored while an amputated piece of a planarian is regenerating its brain? If it is stored in patterns of electric potential, then the same arsenal of chemicals that Levin has used to manipulate electric potentials in other contexts should be effective for studying the mechanism of extra-neural memory.<\/p>\n<ol>\n<li><img decoding=\"async\" src=\"https:\/\/rsscience.com\/wp-content\/uploads\/2021\/10\/planarian-regeneration-1024x654.jpg?ezimgfmt=rs:703x449\/rscb1\/ng:webp\/ngcb1\" alt=\"planarian-regeneration\" \/><\/li>\n<\/ol>\n<p>Plant memory is well-established, thanks to the meticulous work of Gagliano, but inertia is keeping researchers from flocking to the field. There is some foundational work, and I was surprised to learn that\u00a0<a href=\"https:\/\/sci-hub.se\/https:\/\/link.springer.com\/chapter\/10.1007\/978-3-540-37843-3_17\" target=\"_blank\" rel=\"noopener\">plant electrical signaling<\/a>\u00a0has been studied for 200 years. [<a href=\"https:\/\/onlinelibrary.wiley.com\/doi\/full\/10.1111\/j.1365-3040.2006.01614.x\" target=\"_blank\" rel=\"noopener\">Review<\/a>] Electrical signals would probably be the best place to begin a search for memory in plants. Unlike in animals, electrical signaling in plants is decentralized, a departure from the command-and-control model that we think about so naturally. This suggests that plant memory may have properties of fractal scaling and self-organization that will make for future paradigm shifts concerning flow of biological information.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Learning is a function of the brain. Memory is stored in synapses, the connections between neurons. They become stronger each time a connection takes place. \u201cNeurons that fire together, wire together.\u201d This theory was put forward by\u00a0Donald Hebb in 1949, and it is, at best,\u00a0one small part\u00a0of the story.\u00a0It may be completely false. I will &#8230; <a title=\"Where is memory stored?\" class=\"read-more\" href=\"https:\/\/scienceblog.com\/experimentalfrontiers\/2021\/12\/12\/where-is-memory-stored\/\" aria-label=\"Read more about Where is memory stored?\">Read more<\/a><\/p>\n","protected":false},"author":65,"featured_media":71,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":"","jetpack_post_was_ever_published":false},"categories":[1],"tags":[],"class_list":["post-69","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-uncategorized","generate-columns","tablet-grid-50","mobile-grid-100","grid-parent","grid-50"],"yoast_head":"<!-- This site is optimized with the Yoast SEO Premium plugin v27.7 (Yoast SEO v27.7) - https:\/\/yoast.com\/product\/yoast-seo-premium-wordpress\/ -->\n<title>Where is memory stored? - Experimental Frontiers, with Josh Mitteldorf<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/scienceblog.com\/experimentalfrontiers\/2021\/12\/12\/where-is-memory-stored\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Where is memory stored?\" \/>\n<meta property=\"og:description\" content=\"Learning is a function of the brain. Memory is stored in synapses, the connections between neurons. They become stronger each time a connection takes place. \u201cNeurons that fire together, wire together.\u201d This theory was put forward by\u00a0Donald Hebb in 1949, and it is, at best,\u00a0one small part\u00a0of the story.\u00a0It may be completely false. I will ... 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The surprising fact that our bodies are genetically programmed to age and to die offers an enormous opportunity for medical intervention. It may be that therapies to slow the progress of aging need not repair or regenerate anything, but only need to interfere with an existing program of self-destruction. Mitteldorf has taught a weekly yoga class for thirty years. He is an advocate for vigorous self care, including exercise, meditation and caloric restriction. After earning a PhD in astrophysicist, Mitteldorf moved to evolutionary biology as a primary field in 1996. He has taught at Harvard, Berkeley, Bryn Mawr, LaSalle and Temple University. He is presently affiliated with MIT as a visiting scholar. In private life, Mitteldorf is an advocate for election integrity as well as public health. He is an avid amateur musician, playing piano in chamber groups, French horn in community orchestras. His two daughters are among the first children adopted from China in the mid-1980s. Much to the surprise of evolutionary biologists, genetic experiments indicate that aging has been selected as an adaptation for its own sake. This poses a conundrum: the impact of aging on individual fitness is wholly negative, so aging must be regarded as a kind of evolutionary altruism. Unlike other forms of evolutionary altruism, aging offers benefits to the community that are weak, and not well focussed on near kin of the altruist. 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