MedicalResearch.com Interview with:
Samuel Schacher, PhD and
Jiangyuan Hu, PhD,
Department of Neuroscience
Columbia University Medical Cente
New York State Psychiatric Institute
New York, NY 10032, USA
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: It is well established that learning and memory requires changes in the properties of specific neural circuits in the brain activated by the experience. The long-term storage of the memory is encoded through changes in the function of the synapses within the circuit. Synapses are sites of communication between neurons, and the changes in their function come in two varieties: increases in strength and decreases in strength. The encoding of memories typically requires some combination of these synaptic changes, synaptic plasticity, which can last a long time to contribute to long-term memory. Thus the maintenance of a memory will require the persistent change (long-term synaptic memory) in the function of specific synapses.
But memories come in different flavors. In the original experiment by Pavlov, a neutral tone, which dogs ignore, came to predict the immediate appearance of a meal. After several of these pairings, the dogs would become happily excited just with the tone. The same type of conditioning could have a negative valence – the tone could proceed a shock to one of the dog’s paw. Now the neutral tone would predict a negative stimulus and the dog would express fearful behavior just with the tone (associative learning). A non-associative form of memory would be the same types of stimuli but without the preceding neutral stimulus. At random times the animal will be given a meal or a shock. The behavior of the animal for some time will take on the positive or negative features of its environment – a contented versus depressed condition.
Each of these forms of long-term memory would be maintained by increases in the strength of specific synapses.
The questions addressed in our study published in Current Biology, based on previous work in my lab and the lab of my colleague Wayne Sossin at McGill, were:
1) Do the same molecules maintain increases in synaptic strength in the neurons of the circuit after stimuli that produce long-term classical conditioning (associative learning) and long-term sensitization (non-associative learning)?
2) If different molecules maintain the different synaptic memories, is it possible to reverse or erase the different synaptic memories by interfering with the function of the different molecules?
3) If true, can we reverse the different synaptic memories expressed in the same neuron by interfering with the function of the different molecules.
MedicalResearch.com: What are the main findings?
Response: In previous work we demonstrated that the answer was no to question 1 and yes to question 2. The answer to question 3 was described in the Current Biology paper. Yes, interfering with different molecules in one neuron can selective erase the different forms of long-term synaptic memories. One group of molecules maintained the associative synaptic memory but not the non-associative synaptic memory. Interfering with these molecules would selectively erase the associative synaptic memory. In contrast, in the same neuron another group of molecules maintained the non-associative synaptic memory, but not the associative synaptic memory. Interfering with the function of this group of molecules would selectively erase the non-associative synaptic memory.
MedicalResearch.com: What should readers take away from your report?
Response: What makes the results reported in the Current Biology paper promising is that the molecules we examined are expressed in mouse and man and have been found to participate in long-term memory and long-tern synaptic plasticity. Homologous forms of the PKMs and KIBRA, in particular, are expressed in mouse and man. In elderly people with Alzheimers and old-age forms of dementia, the expression of KIBRA is compromised. People with KIBRA mutations show very strong intellectual disabilities. This provided the initial step in identifying and understanding the types of molecules that participate in maintaining different memories.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: The results of the paper provide additional impetus to explore the panoply of different molecules contributing to the maintenance of different forms of synaptic plasticity/memory. Once the catalogue of molecules is available, the design of specific drugs to affect the function of specific molecules can be examined in more ‘advanced’ animal models and hopefully designed for use in humans. An increasing number of people suffer from various anxieties. This inability of controlling one’s life is quite debilitating to those who suffer from anxieties. Designing therapies based on experimental results described in the paper would obviously bring relief to those who suffer, but also provide another compelling reason for society to continue to support basic science, that provide the foundation for the intelligent design of therapies and drugs.
MedicalResearch.com: Is there anything else you would like to add?
Response: Of course, there are ethical issues about developing these types of drugs that can be misused for nefarious purposes or for abusing human rights. As is the case for all such drugs, government and society must regulate how such drugs are distributed and the proper protocols for its use.
MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.
Jiangyuan Hu , Larissa Ferguson , Kerry Adler , Carole A. Farah , Margaret H. Hastings , Wayne S. Sossin , Samuel Schacher. Selective Erasure of Distinct Forms of Long-Term Synaptic Plasticity Underlying Different Forms of Memory in the Same Postsynaptic Neuron. Current Biology, 2017 DOI: 10.1016/j.cub.2017.05.081
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