Suppression of Depression-Like Behavior by Activation of Positive Memories

Technology #18017

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Inventors
Professor Susumu Tonegawa
Department of Biology, MIT
External Link (tonegawalab.org)
Steve Ramirez Moreno
Department of Brain & Cognitive Science, MIT
Xu Liu
Picower Institute For Learning & Memory, Howard Hughes Medical Institute
Christopher MacDonald
Picower Institute For Learning & Memory, MIT
Anthony Moffa
Picower Institute For Learning & Memory, MIT
Joanne Zhou
Department of Biology, MIT
Roger Redondo Pena
Picower Institute For Learning & Memory, Howard Hughes Medical Institute
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Michelle Hunt
MIT Technology Licensing Officer
Patent Protection

Methods and Compositions for Treating Mental Disorders and Conditions

PCT Patent Application WO 2016-205518
Publications
Activating positive memory engrams suppresses depression-like behaviour
Nature , (2015) V.522:7556, pp. 335-339
Engram cells retain memory under retrograde amnesia
Science , (2015) V.348:6238, pp. 1007-1013

Applications

  • Artificial memory manipulation in the mammalian brain
  • Treatments for neurodegenerative disorders - artificially restore, and thereby fix, the brain circuits compromised in neurodegenerative disorders such as Alzheimer
  • Psychotherapeutics - artificially restore positive moods in patients afflicted with depression or dampen down the emotional trauma associated with a memory in patients with PTSD and a variety of anxiety disorders

Problem Addressed

Currently available psychopharmacological treatments generally take weeks to remit the symptoms of psychiatric disorders, and the effectiveness of the treatment varies greatly due to the complex etiology and pathophysiology of psychiatric disorders.  Moreover, despite the promising outcomes of positive cognitive psychotherapy in human, how positive memories interact with psychiatric-disease-related episodes on neuronal level remains largely unknown. 

Technology

Developed in the Laboratory of Nobel laureate Susumu Tonegawa, this invention presents a method that enables identification and labeling of active brain cells during the formation of a memory and subsequent optogenetic manipulation of these brain cells.  With this method, the team in the Tonegawa Laboratory demonstrated for the first time that a defined set of cells in the brain is sufficient to elicit memory recall, building a novel experimental bridge between memory engrams in the brain and animal models of psychiatric disorders.  Reactivation of dentate gyrus engram cells, which were previously active during a positive experience, can potentially suppress symptoms of psychiatric disorders, providing a novel therapeutic intervention to suppress or prevent maladaptive behaviors.  This system in theory can be used in any mammalian brain to artificially manipulate memories.   

Advantages

  • Permits researchers to isolate virtually any kind of memory in the mammalian brain and activate or inactivate it at any defined period of an animal’s life
  • Targets a specific memory in the brain rather than indiscriminately targeting a patch of neural tissue (e.g. with deep brain stimulation) or the entire brain (e.g. with psychotherapeutic drugs)