Date: 11 Jul 2011
How the traumatic memory is formed? The hippocampus plays a central role in learning and memory. However, the molecular and cellular mechanisms underlying hippocampus-dependent traumatic fear memory formation is poorly understood.
Professor Takuya Takahashi and his colleagues at Yokohama City University (and Albert Einstein College of Medicine, NY, USA) present a comprehensive study that explains how traumatic fear memory is formed in the rat on a molecular and cellular level. In this study, they delineate the molecular and cellular mechanisms underlying traumatic fear memory formation. Understanding the molecular mechanism through which traumatic fear memory is established will further our knowledge of how to selectively control aversive traumatic memories.
This study will be published in the July issue of Proceedings of the National Academy of Sciences (July 11th 15:00 EST 2011) .
This study was mainly funded by “Development of biomarker candidates for social behavior” carried out under the Strategic Research Program for Brain Sciences by the Ministry of Education, Culture, Sports,Science and Technology of Japan, and Special Coordination Funds for Promoting Science and Technology.
Background and results
The majority of excitatory synapses in the mammalian central nervous system use glutamate as a neurotransmitter. Fast glutamatergic transmission is mainly mediated by AMPA (α-amino-3-hydroxy- 5-methyl-4-isoxazole propionic acid) type ionotropic glutamate receptors (AMPARs) (Figure). AMPARs are tetramers comprised of a combinatorial assembly of four subunits, GluR1-4. Synaptic plasticity at glutamatergic synapses is considered to be crucial for cognitive functions such as learning and memory. The best-studied form of synaptic plasticity is LTP (Long-term potentiation), and its molecular mechanisms have been extensively characterized. Synaptic delivery and addition of AMPARs appears to be a major mechanism regulating postsynaptic expression of LTP. LTP inducing stimuli in vitro drive GluR1-containing AMPARs into synapses and enhance synaptic transmission. The same molecular modification occurs during experience-dependent neuronal reorganization in vivo (Figure). Sensory experience early in development delivers GluR1 into synapses of the rodent barrel cortex which receives input from whiskers.
In this study, Professor Takuya Takahashi and his colleagues at Yokohama City University (and Albert Einstein College of Medicine, NY, USA) showed that the inhibitory avoidance (IA) task, a hippocampus-dependent contextual fear learning paradigm, delivered GluR1-containing AMPARs into CA3-CA1 synapses of the dorsal hippocampus. Furthermore, a blockade of GluR1-dependent synaptic plasticity in this brain area largely attenuated IA learning, indicating that synaptic GluR1 trafficking in the hippocampus is necessary for encoding contextual fear memories. The fraction of CA1 neurons which underwent synaptic strengthening positively correlated with the performance in the IA fear memory task. Thus, the robustness of a contextual memory depends on the number of hipppocampal neurons that participate in the encoding of a traumatic memory trace.
This study presents the molecular and cellular mechanisms underlying traumatic fear memory formation. Understanding the molecular mechanism through which traumatic fear memory is established will further our knowledge of how to selectively control averse traumatic memories.
For inquiries regarding this press release
Takuya Takahashi M.D. Ph.D
Professor, Department of Physiology, Graduate School of Medicine, Yokohama City University