Modifying Hippocampal Memory

It's been long documented that our memories are modified by the act of remembering, and that the emotional circumstance of that act of recalling influences future emotional content of that memory on future recalling. This process is part of memory consolidation, where a memory becomes part of our background knowledge.

See, for example, Bridge and Paller in The Journal of Neuroscience here.

There's no known natural brain process that some neuroscientist has not at least tried to duplicate via technology. In the below study, we have electrode-implanted mice which were selected for the electrodes activating a particular situation's (situation A) memory tracing (a la Wilder Penfield's human studies). Forced recall via electrode stimulation of a non-painful memory was coupled with a painful stimulus (situation B).

As a result, the experiment showed that the mice became conditioned to expect pain when put in the recalled situation A again for real.

No, this is not Total Recall. The memory had its emotional content modified, not its overall content. Still, one wonders if this could be made into a treatment for PTSD someday.

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ABSTRACT

Creating a False Memory in the Hippocampus

Steve Ramirez1,*, Xu Liu1,2,*, Pei-Ann Lin1, Junghyup Suh1, Michele Pignatelli1, Roger L. Redondo1,2, Tom├ís J. Ryan1,2, Susumu Tonegawa1,2,†

Memories can be unreliable. We created a false memory in mice by optogenetically manipulating memory engram–bearing cells in the hippocampus. Dentate gyrus (DG) or CA1 neurons activated by exposure to a particular context were labeled with channelrhodopsin-2. These neurons were later optically reactivated during fear conditioning in a different context. The DG experimental group showed increased freezing in the original context, in which a foot shock was never delivered. The recall of this false memory was context-specific, activated similar downstream regions engaged during natural fear memory recall, and was also capable of driving an active fear response. Our data demonstrate that it is possible to generate an internally represented and behaviorally expressed fear memory via artificial means.

Science 26 July 2013: Vol. 341 no. 6144 pp. 387-391 DOI: 10.1126/science.1239073

Stem Cells Treat Metatchromatic Leukodystrophy


Metachromatic  leukodystrophy is a genetic brain disease.  The exciting thing in the report below is that just using GMO stem cells (viral carrier for the corrected gene) to correct the bone marrow DNA was enough to arrest the disease, at least as far as was reported--the treatment is too new to report long term results.
The (potentially) cured patients would be GMO people, but be all the healthier for that.

Science DOI: 10.1126/science.1233158
  • RESEARCH ARTICLE

Lentiviral Hematopoietic Stem Cell Gene Therapy Benefits Metachromatic Leukodystrophy

  1. Luigi Naldini1,4,§
+Author Affiliations
  1. 1San Raffaele Telethon Institute for Gene Therapy (TIGET), San Raffaele Scientific Institute, 20132 Milan, Italy.
  2. 2TIGET Pediatric Clinical Research Unit, Division of Regenerative Medicine, Stem Cells and Gene Therapy, San Raffaele Scientific Institute, 20132 Milan, Italy.
  3. 3Pediatric Immunohematology and Bone Marrow Transplant Unit, San Raffaele Scientific Institute, 20132 Milan, Italy.
  4. 4Vita-Salute San Raffaele University, 20132 Milan, Italy.
  5. 5Neurology Unit, Department of Neurology, San Raffaele Scientific Institute, 20132 Milan, Italy.
  6. 6Neuroradiology Unit, Head and Neck Department, San Raffaele Scientific Institute, 20132 Milan, Italy.
  7. 7Department of Experimental Medicine and Biochemical Sciences, University of Perugia, 06122 Perugia, Italy.
  8. 8MolMed S.p.A., 20132 Milan, Italy.
  9. 9Distributed Computing Group, Center for Advanced Studies, Research and Development in Sardinia (CRS4), 09010 Pula, Italy.
  10. 10Pediatric Hematology Oncology Division, Rafic Hariri University Hospital, Beirut, Lebanon.
  11. 11Department of Pediatrics, University of Nebraska Medical Center, Omaha, NE 68198, USA.
  12. 12Molecular and Cellular Technologies, GlaxoSmithKline, Stevenage 5G1 2NY, UK.
  13. 13Pediatric Blood and Marrow Transplantation Program, University Medical Center 3584 CX Utrecht, Netherlands.
  14. 14Department of Translational Oncology, National Center for Tumor Diseases and German Cancer Research Center, 69120 Heidelberg, Germany.
  15. 15Hematology and Bone Marrow Transplant Unit, San Raffaele Scientific Institute, 20132 Milan, Italy.
  16. 16Center for Translational Genomics and BioInformatics, San Raffaele Scientific Institute, 20132 Milan, Italy.
  17. 17Regenerative Medicine Discovery Performance Unit, GlaxoSmithKline Research and Development, King of Prussia, PA 19406, USA.
  18. 18Bone Marrow Transplant Unit, MBBM Foundation, Pediatric Department, Milano-Bicocca University at San Gerardo Hospital, 20052 Monza, Italy.
  19. 19University of Rome Tor Vergata, 00133 Rome, Italy.
  1. §To whom correspondence should be addressed. E-mail: biffi.alessandra@hsr.it (A.B.); naldini.luigi@hsr.it (L.N.)
  1. * These authors contributed equally to this work.
Metachromatic leukodystrophy (MLD) is an inherited lysosomal storage disease caused by arylsulfatase A (ARSA) deficiency. Patients with MLD exhibit progressive motor and cognitive impairment and die within few years of symptom onset. We used a lentiviral vector to transfer a functional ARSA gene into hematopoietic stem cells (HSCs) from three presymptomatic patients who showed genetic, biochemical, and neurophysiological evidence of late infantile MLD. After reinfusion of the gene-corrected HSCs, the patients showed extensive and stable ARSA gene replacement, which led to high enzyme expression throughout hematopoietic lineages and in cerebrospinal fluid. Analyses of vector integrations revealed no evidence of aberrant clonal behavior. Notably, the disease did not manifest or progress in the three patients 7 to 21 months beyond the predicted age of symptom onset. These findings indicate that extensive genetic engineering of human hematopoiesis can be achieved with lentiviral vectors and that this approach may offer therapeutic benefit for MLD patients.

An alternative to Kim's physicalism

In his book Physicalism, or Something Near Enough , Jaegwon Kim says: The final picture that has emerged is this: P is a cause of P*, wi...