Summary: Researchers report memories that trigger PTSD and anxiety can be erased without affecting other memories.
Source: Columbia University.
New study of snail neurons suggests memories that trigger anxiety, PTSD could be ‘erased’ without affecting normal memory of past events.
Different types of memories stored in the same neuron of the marine snail Aplysia can be selectively erased, according to a new study by researchers at Columbia University Medical Center (CUMC) and McGill University and published today in Current Biology.
The findings suggest that it may be possible to develop drugs to delete memories that trigger anxiety and post-traumatic stress disorder (PTSD) without affecting other important memories of past events.
During emotional or traumatic events, multiple memories can become encoded, including memories of any incidental information that is present when the event occurs. In the case of a traumatic experience, the incidental, or neutral, information can trigger anxiety attacks long after the event has occurred, say the researchers.
“The example I like to give is, if you are walking in a high-crime area and you take a shortcut through a dark alley and get mugged, and then you happen to see a mailbox nearby, you might get really nervous when you want to mail something later on,” says Samuel Schacher, PhD, a professor of neuroscience in the Department of Psychiatry at CUMC and co-author of the paper. In the example, fear of dark alleys is an associative memory that provides important information — e.g., fear of dark alleys — based on a previous experience. Fear of mailboxes, however, is an incidental, non-associative memory that is not directly related to the traumatic event.
“One focus of our current research is to develop strategies to eliminate problematic non-associative memories that may become stamped on the brain during a traumatic experience without harming associative memories, which can help people make informed decisions in the future — like not taking shortcuts through dark alleys in high-crime areas,” Dr. Schacher adds.
Brains create long-term memories, in part, by increasing the strength of connections between neurons and maintaining those connections over time. Previous research suggested that increases in synaptic strength in creating associative and non-associative memories share common properties. This suggests that selectively eliminating non-associative synaptic memories would be impossible, because for any one neuron, a single mechanism would be responsible for maintaining all forms of synaptic memories.
The new study tested that hypothesis by stimulating two sensory neurons connected to a single motor neuron of the marine snail Aplysia; one sensory neuron was stimulated to induce an associative memory and the other to induce a non-associative memory.
By measuring the strength of each connection, the researchers found that the increase in the strength of each connection produced by the different stimuli was maintained by a different form of a Protein Kinase M (PKM) molecule (PKM Apl III for associative synaptic memory and PKM Apl I for non-associative). They found that each memory could be erased – without affecting the other — by blocking one of the PKM molecules.
In addition, they found that specific synaptic memories may also be erased by blocking the function of distinct variants of other molecules that either help produce PKMs or protect them from breaking down.
The researchers say that their results could be useful in understanding human memory because vertebrates have similar versions of the Aplysia PKM proteins that participate in the formation of long-term memories. In addition, the PKM-protecting protein KIBRA is expressed in humans, and mutations of this gene produce intellectual disability.
“Memory erasure has the potential to alleviate PTSD and anxiety disorders by removing the non-associative memory that causes the maladaptive physiological response,” says Jiangyuan Hu, PhD, an associate research scientist in the Department of Psychiatry at CUMC and co-author of the paper. “By isolating the exact molecules that maintain non-associative memory, we may be able to develop drugs that can treat anxiety without affecting the patient’s normal memory of past events.”
“Our study is a ‘proof of principle’ that presents an opportunity for developing strategies and perhaps therapies to address anxiety,” said Dr. Schacher. “For example, because memories are still likely to change immediately after recollection, a therapist may help to ‘rewrite’ a non-associative memory by administering a drug that inhibits the maintenance of non-associative memory.”
Future studies in preclinical models are needed to better understand how PKMs are produced and localized at the synapse before researchers can determine which drugs may weaken non-associative memories.
Two Aplysia sensory neurons with synaptic contacts on the same motor neuron in culture after isolation from the nervous system of Aplysia. The motor neuron has been injected with a fluorescent molecule that blocks the activity of a specific Protein Kinase M molecule. (Credit: Schacher Lab/Columbia University Medical Center)
The other authors are Jiangyuan Hu (CUMC), Larissa Ferguson (McGill University, Montreal, Quebec, Canada), Kerry Adler (CUMC), Carole A. Farah (McGill), Margaret H. Hastings (McGill), and Wayne S. Sossin (McGill).
The authors report no financial or other conflicts of interest.
Funding: The research was supported by the National Institutes of Health (MH 060387) and the Canadian Institutes of Health (MOP 12046 and 340328).
Source: Helen Garey – Columbia University
Image Source: NeuroscienceNews.com image is credited to Schacher Lab/Columbia University Medical Center.
Original Research: Abstract for “Selective Erasure of Distinct Forms of Long-Term Synaptic Plasticity Underlying Different Forms of Memory in the Same Postsynaptic Neuron” by Jiangyuan Hu, Larissa Ferguson, Kerry Adler, Carole A. Farah, Margaret H. Hastings, Wayne S. Sossin, and Samuel Schacher in Neuron. Published online June 22 2017 doi:10.1016/j.cub.2017.05.081
[cbtabs][cbtab title=”MLA”]Columbia University “Select Memories Can Be Erased, Leaving Others Intact.” NeuroscienceNews. NeuroscienceNews, 22 June 2017.
<https://neurosciencenews.com/ptsd-delete-selected-memories-6961/>.[/cbtab][cbtab title=”APA”]Columbia University (2017, June 22). Select Memories Can Be Erased, Leaving Others Intact. NeuroscienceNew. Retrieved June 22, 2017 from https://neurosciencenews.com/ptsd-delete-selected-memories-6961/[/cbtab][cbtab title=”Chicago”]Columbia University “Select Memories Can Be Erased, Leaving Others Intact.” https://neurosciencenews.com/ptsd-delete-selected-memories-6961/ (accessed June 22, 2017).[/cbtab][/cbtabs]
Abstract
Selective Erasure of Distinct Forms of Long-Term Synaptic Plasticity Underlying Different Forms of Memory in the Same Postsynaptic Neuron
Highlights
•Distinct forms of persistent plasticity co-exist in the same neuron
•Separate perturbations erase distinct forms of plasticity in the same neuron
•Separate PKMs and calpains are needed for distinct plasticities in the same neuron
•The adaptor protein KIBRA stabilizes an atypical PKM to maintain one form of plasticity
Summary
Generalization of fear responses to non-threatening stimuli is a feature of anxiety disorders. It has been challenging to target maladaptive generalized memories without affecting adaptive memories. Synapse-specific long-term plasticity underlying memory involves the targeting of plasticity-related proteins (PRPs) to activated synapses. If distinct tags and PRPs are used for different forms of plasticity, one could selectively remove distinct forms of memory. Using a stimulation paradigm in which associative long-term facilitation (LTF) occurs at one input and non-associative LTF at another input to the same postsynaptic neuron in an Aplysia sensorimotor preparation, we found that each form of LTF is reversed by inhibiting distinct isoforms of protein kinase M (PKM), putative PRPs, in the postsynaptic neuron. A dominant-negative (dn) atypical PKM selectively reversed associative LTF, while a dn classical PKM selectively reversed non-associative LTF. Although both PKMs are formed from calpain-mediated cleavage of protein kinase C (PKC) isoforms, each form of LTF is sensitive to a distinct dn calpain expressed in the postsynaptic neuron. Associative LTF is blocked by dn classical calpain, whereas non-associative LTF is blocked by dn small optic lobe (SOL) calpain. Interfering with a putative synaptic tag, the adaptor protein KIBRA, which protects the atypical PKM from degradation, selectively erases associative LTF. Thus, the activity of distinct PRPs and tags in a postsynaptic neuron contribute to the maintenance of different forms of synaptic plasticity at separate inputs, allowing for selective reversal of synaptic plasticity and providing a cellular basis for developing therapeutic strategies for selectively reversing maladaptive memories.
“Selective Erasure of Distinct Forms of Long-Term Synaptic Plasticity Underlying Different Forms of Memory in the Same Postsynaptic Neuron” by Jiangyuan Hu, Larissa Ferguson, Kerry Adler, Carole A. Farah, Margaret H. Hastings, Wayne S. Sossin, and Samuel Schacher in Neuron. Published online June 22 2017 doi:10.1016/j.cub.2017.05.081
