Schizophrenia Research Forum - A Catalyst for Creative Thinking


Ramirez S, Liu X, Lin PA, Suh J, Pignatelli M, Redondo RL, Ryan TJ, Tonegawa S. Creating a false memory in the hippocampus. Science. 2013 Jul 26 ; 341(6144):387-91. Pubmed Abstract

Comments on News and Primary Papers


Primary Papers: Creating a false memory in the hippocampus.

Comment by:  Tobias Bast
Submitted 6 August 2013
Posted 6 August 2013

This is a very interesting story, considering the new findings by Ramirez and colleagues (2013) in relation to ideas that aberrant hippocampal activity in schizophrenia may cause delusions by laying down faulty memories (Tamminga et al., 2012). However, the metabolic overactivity observed in the hippocampus of schizophrenia patients (Schobel et al., 2009), possibly caused by reduced function of GABAergic inhibitory interneurons (Heckers and Konradi, 2010), is very different from the specific activation of distinct hippocampal neuron populations that caused false memories in mice in the study by Ramirez et al. Such hippocampal overactivity, rather than generating false memories, may contribute to schizophrenia symptoms, including cognitive deficits and psychosis, by alternative mechanisms. For example, hippocampal overactivity in schizophrenia may interfere with hippocampus-dependent memory tasks by disrupting temporal and spatial specificity of hippocampal neuron activity and may cause psychotic symptoms by way of aberrant drive of the brain dopamine system (e.g., Lodge and Grace, 2011; Bast, 2011).

References:

Tamminga CA, Southcott S, Sacco C, Wagner AD, Ghose S. Glutamate dysfunction in hippocampus: relevance of dentate gyrus and CA3 signaling. Schizophr Bull. 2012 Sep;38(5):927-35. Abstract

Schobel SA, Lewandowski NM, Corcoran CM, Moore H, Brown T, Malaspina D, Small SA. Differential targeting of the CA1 subfield of the hippocampal formation by schizophrenia and related psychotic disorders. Arch Gen Psychiatry. 2009 Sep;66(9):938-46. Abstract

Heckers S, Konradi C. Hippocampal pathology in schizophrenia. Curr Top Behav Neurosci. 2010;4:529-53. Abstract

Lodge DJ, Grace AA. Hippocampal dysregulation of dopamine system function and the pathophysiology of schizophrenia. Trends Pharmacol Sci. 2011 Sep;32(9):507-13. Abstract

Bast T. The hippocampal learning-behavior translation and the functional significance of hippocampal dysfunction in schizophrenia. Curr Opin Neurobiol. 2011 Jun;21(3):492-501. Abstract

View all comments by Tobias Bast

Primary Papers: Creating a false memory in the hippocampus.

Comment by:  Scott Small
Submitted 6 August 2013
Posted 6 August 2013

This is an extremely elegant paper by a group that continues to use state-of-the-art tools to expand our understanding of hippocampal-dependent memory. In the past the group has combined transgenic engineering with optogenetics to show how the dentate gyrus—a region within the hippocampus—plays a critical role in encoding normal memories. In this new study, they show how, when abnormally stimulated, the dentate gyrus can play a role in forming false memories.

I think this research is more relevant to PTSD than to psychosis. Some studies have implicated the dentate gyrus in PTSD, and false memories seem more related to symptoms of PTSD.

View all comments by Scott Small