Long-term potentiation (LTP) is widely assumed to be the mechanism by which memory traces are encoded and stored (1-15). From Martin and colleagues, the synaptic plasticity and memory hypothesis states that """"""""activity-dependent synaptic plasticity is induced at appropriate synapses during memory formation and is both necessary and sufficient for the information storage underlying the type of memory mediated by the brain area in which that plasticity is observed."""""""" There is a great deal of evidence demonstrating that synaptic plasticity is necessary for learning and memory, but there is no convincing evidence supporting the notion of sufficiency (14). While numerous studies have shown that certain types of learning can occlude LTP in relevant brain regions (10-13,15-20), LTP has yet to be proven to occlude learning. Until now, technological limitations have precluded a convincing demonstration of LTP occlusion of learning, as delivering a tetanus with an electrode may have direct and indirect circuit-wide repercussions. With the recent advent and application of ChannelRhodopsin2 (ChR2) used in vivo (21-23) by the Deisseroth laboratory, where I will be working, and other groups, the tools are now available to selectively induce LTP into a specific subset of synapses thought to be important for associative learning. I hypothesize that selectively inducing LTP in the thalamo- amygdala pathway by using ChR2 will first occlude acquisition of a cue-outcome association, but will subsequently enhance the basal capacity of this pathway to be potentiated, thereby enhancing the aptitude for associative learning. I will test this hypothesis by first (Specific Aim 1) developing a novel method of inducing LTP in a specific subset of synapses using ChR2, and then by (Specific Aim 2) testing the learning ability of these rats at various time points after ChR2-LTP induction. These experiments will allow us to draw conclusions about the time course of the neurophysiological changes that mediate memory formation and storage with confidence

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Postdoctoral Individual National Research Service Award (F32)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-F02A-J (20))
Program Officer
Vogel, Michael W
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Stanford University
Biomedical Engineering
Schools of Medicine
United States
Zip Code
Kim, Sung-Yon; Adhikari, Avishek; Lee, Soo Yeun et al. (2013) Diverging neural pathways assemble a behavioural state from separable features in anxiety. Nature 496:219-23
Warden, Melissa R; Selimbeyoglu, Aslihan; Mirzabekov, Julie J et al. (2012) A prefrontal cortex-brainstem neuronal projection that controls response to behavioural challenge. Nature 492:428-32
Tye, Kay M; Prakash, Rohit; Kim, Sung-Yon et al. (2011) Amygdala circuitry mediating reversible and bidirectional control of anxiety. Nature 471:358-62
Mattis, Joanna; Tye, Kay M; Ferenczi, Emily A et al. (2011) Principles for applying optogenetic tools derived from direct comparative analysis of microbial opsins. Nat Methods 9:159-72