Engineering a memory with LTD and LTP

By S. Nabavi, R. Fox, Christophe D. Proulx, John Y. Lin, Roger Tsien, R. Malinow. Nature, 2014

929 citations recorded by the source corpus.

It has been proposed that memories are encoded by modification of synaptic strengths through cellular mechanisms such as long-term potentiation (LTP) and long-term depression (LTD). However, the causal link between these synaptic processes and memory has been difficult to demonstrate. Here we show that fear conditioning, a type of associative memory, can be inactivated and reactivated by LTD and LTP, respectively. We began by conditioning an animal to associate a foot shock with optogenetic stimulation of auditory inputs targeting the amygdala, a brain region known to be essential for fear conditioning. Subsequent optogenetic delivery of LTD conditioning to the auditory input inactivates memory of the shock. Then subsequent optogenetic delivery of LTP conditioning to the auditory input reactivates memory of the shock. Thus, we have engineered inactivation and reactivation of a memory using LTD and LTP, supporting a causal link between these synaptic processes and memory.

Subfields: Cellular and Molecular Neuroscience, Cognitive Neuroscience

View Paper: https://www.semanticscholar.org/paper/925ada6dcfd0d99185e9b214c2db7063dd91f3b3

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In Cellular and Molecular Neuroscience

In Cognitive Neuroscience

Citations in the corpus

Models of Metaplasticity: A Review of Concepts (2015, background): “While this instability can be avoided by artificially imposing hard boundaries onto the synaptic weights, several learning models came with intrinsic mechanisms regulating the synaptic efficacies (Bienenstock et al., 1982; Oja, 1982) in order to solve this issue in a less fine-tuned manner.”
Memory engrams: Recalling the past and imagining the future (2020, result): “The idea that engrams may be silenced by disrupting synaptic efficacy and spine density and reawakened by enhancing synaptic plasticity is consistent with findings from a nonengram study examining auditory fear conditioning (161).”
Synaptic Plasticity Forms and Functions. (2020, background): “…have been shown to profoundly alter standard correlative types of synaptic plasticity in a concentration-and receptor subtype–dependent manner, and this has led to the concept that specific neuromodulators could gate Hebbian plasticity (Gu 2002, Nadim & Bucher 2014, Brzosko et al. 2017).”
Closed-loop and activity-guided optogenetic control. (2015, positive): “Several studies have recently used projection-recruitment methods to show causal significance for plasticity in defined projections in mammalian behavior (Nabavi et al., 2014; Creed et al., 2015).”
How can memories last for days, years, or a lifetime? Proposed mechanisms for maintaining synaptic potentiation and memory (2019, background): “These mechanisms contribute to memory formation, and their contribution depends on the type of learning and the brain region involved (Whitlock et al. 2006; Ito et al. 2014; Nabavi et al. 2014; Mirisis et al. 2016; Jörntell 2017).”
The Persistence and Transience of Memory. (2017, methodology): “The ﬁrst of these used a Pavlovian fear conditioning paradigm (Nabavi et al., 2014).”
Interaction between BDNF Val66Met polymorphism and mismatch negativity for working memory capacity in schizophrenia (2024, background): “Given that the BDNF Val/Met polymorphism may in ﬂ uence NMDAR-dependent long-term potentiation and depression 29,30 , which are foundational for memory 33 , we hypothesized that the relationship between MMN amplitude and working memory would be regulated by the BDNF Val/Met polymorphism.”