Summary: Researchers have shed new light on the molecular and genetic basis of long-term memory formation in the brain. A new study reveals that a single stimulation of hippocampal neuron synapses triggered numerous cycles where the Arc gene encoding memory produced mRNA molecules that were then translated into synapse-strengthening Arc proteins. From the results, the researchers determined a novel feedback loop that helps explain how mRNA and short-lived proteins create long-term memories in the brain.
Source: Albert Einstein College of Medicine
Helping his mother make pancakes when you were three…riding a bike without training wheels…your first romantic kiss: How do we retain vivid memories of past events?
As described in an article published online April 25 in neuronresearchers from the Albert Einstein College of Medicine have found the explanation.
“The ability to learn new information and store it for long periods of time is one of the most remarkable features of the brain,” said Robert H. Singer, Ph.D., co-corresponding author of the paper. .
“We made a surprising discovery in mice regarding the molecular basis for making these long-term memories.” Dr. Singer is Dominick P. Purpura Professor of Cell Biology and Department of Neuroscience, Emeritus Professor of Anatomy and Structural Biology, and Director of the RNA Biology Program at Einstein.
Some aspects of the cellular basis of memory were already known. They are made by neurons (nerve cells) and stored in a region of the brain called the hippocampus. They form when repeated neural stimulation strengthens synapses, the connections between nerve cells.
Proteins are needed to stabilize the long-lasting synaptic connections necessary for long-term memories. The blueprints of these proteins are messenger RNA (mRNA) molecules which, in turn, are transcribed (copied) from memory-associated genes.
“The paradox is that it takes a long time – several hours – to form a long-lasting memory, but the mRNAs and proteins associated with protein making disappear within an hour,” said Sulagna Das, Ph.D. ., first and co-corresponding author of the paper and Assistant Research Professor of Cell Biology at Einstein. “How could that be?”
To answer this question, the research team developed a mouse model in which they fluorescently labeled all mRNA molecules that leak from Bowan extremely important gene for converting our activities and other experiences into long-term memories.
The researchers stimulated synapses in mouse hippocampal neurons and then, using high-resolution imaging techniques they developed, observed the results in individual nerve cells in real time.
To their amazement, they observed that a single stimulus to the neuron triggered many cycles during which the gene encoding memory Bow produced mRNA molecules that were then translated into synapse-strengthening Arc proteins.
“We saw that some of the protein molecules made from that initial synaptic stimulus go back to Bow and reactivate it, initiating another round of mRNA formation and protein production followed by several more,” Dr. Singer said.
“With each cycle, we saw more and more protein build up to form ‘hot spots’ at the synapse, where memories are cemented in place. We had discovered a previously unknown feedback loop that explained how short-lived mRNAs and proteins can create long-lived memories,” said Dr. Das.
Consider what is involved in memorizing a poem, Dr. Singer suggested: “To create a lasting memory, you must read the poem over and over, and each reading can be thought of as an intermittent stimulus that adds a building protein of memory at the synapse.”
Dr. Das noted that the defective expression of the Bow The gene has been implicated in memory impairment in humans and is linked to neurological disorders including autism spectrum disorders and Alzheimer’s disease. “What we learn BowNeurology’s response to nerve cell stimulation can provide insight into the causes of these health conditions,” she noted.
The article is titled “Maintaining a short-lived protein needed for long-term memory involves cycles of local transcription and translation.” Other Einstein authors include Pablo Lituma, Ph.D., and Pablo Castillo, MD, Ph.D., of the Dominick P. Purpura Department of Neuroscience.
About this memory research news
Author: Elaine Iandoli
Source: Albert Einstein College of Medicine
Contact: Elaine Iandoli – Albert Einstein College of Medicine
Picture: Image is in public domain
Original research: Access closed.
“Maintenance of a short-lived protein necessary for long-term memory involves cycles of local transcription and translation” by Robert H. Singer et al. neuron
Maintaining a short-lived protein required for long-term memory involves cycles of local transcription and translation
- Reactivation of transcription drives the cycle of Bow gene in individual neurons
- Reduced feedback from novel proteins Bow transcription to next cycle
- Bow mRNAs from later cycles localize to sites marked by the previous Arc protein
- Repetitive translation in hotspots consolidates the dendritic arch in selective hubs
Activity-dependent expression of immediate early genes (IEGs) is essential for long-term synaptic remodeling and memory. It remains unclear how IEGs are maintained for memory despite rapid transcript and protein turnover. To solve this puzzle, we monitored Bowan essential IEG for memory consolidation.
Using a knockin mouse where endogenous Bow alleles were fluorescently labeled, we performed real-time imaging of Bow mRNA dynamics in individual neurons in cultures and brain tissue.
Unexpectedly, a single burst stimulation was sufficient to induce cycles of transcriptional reactivation in the same neuron. Subsequent rounds of transcription required translation, whereby new Arc proteins engaged in autoregulatory positive feedback to reinduce transcription.
The following Bow mRNAs preferentially localize to sites marked by the preceding Arc protein, assembling a translation “hotspot” and consolidating dendritic Arc “hubs”.
These cycles of transcription-translation coupling support protein expression and provide a mechanism by which a short-lived event can support long-term memory.