Posts tagged memory formation

Posts tagged memory formation
The Fabric for Weaving Memory
The details of memory formation are still largely unknown. It has, however, been established that the two kinds of memory – long term and short term – use different mechanisms. When short-term memory is formed, certain proteins in the nerve cells (neurons) of the brain are transiently modified. To establish long-term memory, the cells have to synthesize new protein molecules. This has been shown in experiments with animals. When drugs were used to block protein synthesis, the treated animals were not able to form long-term memory.
The precise mechanism by which the newly synthesized proteins regulate memory formation is still poorly understood. They are thought to strengthen existing connections between neurons, as well as establish new connections. Both processes are required for long-term memory formation.
A nerve cell in the brain makes connections with tens of thousands of other nerve cells through so-called synapses. When memory is formed, only specific synapses, which are activated by a specific experience are modified. The mechanism of how the synthesis of new proteins can be restricted to these activated synapses has been unclear. Neurobiologists have postulated the existence of “synaptic tags”. One of the candidates is a family of proteins known to regulate local protein synthesis, the CPEB family of proteins. These proteins have been known for some time to perform important tasks during embryonic development, and recently have been identified in neuronal synapses.
In 2007, Krystyna Keleman, a neuroscientist at the Research Institute of Molecular Pathology (IMP) in Vienna, was able to show that fruit flies require CPEB proteins for long-term memory formation.
To study memory formation, the researchers at the IMP looked at the sexual behavior of flies. After copulation, female flies loose interest in the courtship advances of males. Male flies must learn – by trial and error – that only virgin females are receptive. The key to telling them apart is their smell.

Neuroscientists from New York University and the University of California, Irvine have isolated the “when” and “where” of molecular activity that occurs in the formation of short-, intermediate-, and long-term memories. Their findings, which appear in the journal the Proceedings of the National Academy of Sciences, offer new insights into the molecular architecture of memory formation and, with it, a better roadmap for developing therapeutic interventions for related afflictions.
“Our findings provide a deeper understanding of how memories are created,” explained the research team leader Thomas Carew, a professor in NYU’s Center for Neural Science and dean of NYU’s Faculty of Arts and Science. “Memory formation is not simply a matter of turning molecules on and off; rather, it results from a complex temporal and spatial relationship of molecular interaction and movement.”
Neuroscientists have previously uncovered different aspects of molecular signaling relevant to the formation of memories. But less understood is the spatial relationship between molecules and when they are active during this process.
To address this question, the researchers studied the neurons in Aplysia californica, the California sea slug. Aplysia is a model organism that is quite powerful for this type of research because its neurons are 10 to 50 times larger than those of higher organisms, such as vertebrates, and it possesses a relatively small network of neurons—characteristics that readily allow for the examination of molecular signaling during memory formation. Moreover, its coding mechanism for memories is highly conserved in evolution, and thus is similar to that of mammals, making it an appropriate model for understanding how this process works in humans.
The scientists focused their study on two molecules, MAPK and PKA, which earlier research has shown to be involved in many forms of memory and synaptic plasticity—that is, changes in the brain that occur after neuronal interaction. But less understood was how and where these molecules interacted.
To explore this, the researchers subjected the sea slugs to sensitization training, which induces increased behavioral reflex responsiveness following mild tail shock, or in this study, mild activation of the nerve form the tail. They then examined the subsequent molecular activity of both MAPK and PKA. Both molecules have been shown to be involved in the formation of memory for sensitization, but the nature of their interaction is less clear.
What they found was MAPK and PKA coordinate their activity both spatially and temporally in the formation of memories. Specifically, in the formation of intermediate-term (i.e., hours) and long-term (i.e., days) memories, both MAPK and PKA activity occur, with MAPK spurring PKA action. By contrast, for short-term memories (i.e., less than 30 minutes), only PKA is active, with no involvement of MAPK.
(Source: nyu.edu)
How does one’s experience of an event get translated into a memory that can be accessed months, even years later?
A team led by University of Pennsylvania scientists has come closer to answering that question, identifying key molecules that help convert short-term memories into long-term ones. These proteins may offer a target for drugs that can enhance memory, alleviating some of the cognitive symptoms that characterize conditions including schizophrenia, depression and Parkinson’s and Alzheimer’s diseases.
“There are many drugs available to treat some of the symptoms of diseases like schizophrenia,” Abel -Penn’s Brush Family Professor of Biology- said, “but they don’t treat the cognitive deficits that patients have, which can include difficulties with memory. This study looks for more specific targets to treat deficits in cognition.”
Published in the Journal of Clinical Investigation, the study focused on a group of proteins called nuclear receptors, which have been implicated in the regulation of a variety of biological functions, including memory formation.
Researchers have discovered how to store diverse forms of artificial short-term memories in isolated brain tissue. The advance paves the way for future research to identify the specific brain circuits that allow humans to form short-term memories.
Using isolated pieces of rodent brain tissue, the researchers demonstrated that they could form a memory of which one of four input pathways was activated. The neural circuits contained within small isolated sections of the brain region called the hippocampus maintained the memory of stimulated input for more than 10 seconds. The information about which pathway was stimulated was evident by the changes in the ongoing activity of brain cells.
"The type of activity we triggered in isolated brain sections was similar to what other researchers have demonstrated in monkeys taught to perform short-term memory tasks," according to Mr. Hyde. "Both types of memory-related activity changes typically lasted for 5-10 seconds."
The researchers also demonstrated that they could generate memories for specific contexts, such as whether a particular pathway was activated alone or as part of a sequence of stimuli to different inputs. Changes in ongoing activity of hippocampal neurons accurately distinguished between two temporal sequences, akin to humans recognizing the difference between two different song melodies. The artificial memories Dr. Strowbridge’s group created in the hippocampus continued to recognize each sequence even when the interval between stimuli was changed.
In the insect brain, dopamine-releasing nerve cells are crucial to the formation of both punished and rewarded memories.
Hiromu Tanimoto and his colleagues at the Max Planck Institute of Neurobiology recently localised and identified the most important types of nerve cells involved in forming positive and negative memories of a fruit fly. All four nerve cell types they discovered use dopamine to communicate with other nerve cells. The dopamine signals released by these cells are received in the mushroom body, a prominent brain structure in insect brains. “It is really surprising that similar dopamine-releasing nerve cells can play such different roles,” says Tanimoto.
Read more: Dopamine – A substance with many messages