User:Hmargaret/sandbox

Engrams are theorized to be means by which memories are stored[1] as biophysical or biochemical[2] changes in the brain (and other neural tissue) in response to external stimuli. '''Engram cells, or memory traces, are neurons that have underwent structural alterations when activated by a stimulus. Learning can activate a set of engram cells, and they become connected by neural circuits. This connected group of cells is known as an engram cell pathway. These pathways form an engram complex that stores a specific memory. The reactivation of these engram cells by the original stimuli during learning forms memory recall. '''

The existence of engrams is posited by some scientific theories to explain the persistence of memory and how memories are stored in the brain. The existence of neurologically defined engrams is not significantly disputed, though their exact mechanism and location has been a focus of persistent research for many decades.

The term engram was coined by the little-known but influential memory researcher Richard Semon. '''Semon believed the terms used in relation to memory were not of precise scientific value. This led to him coining and defining many of his own terms to better correspond with his intended meanings. In 1921, he used the word engram to describe “primarily latent modification in the irritable substance produced by a stimulus". This term, “engram”, is similar in meaning to the term “memory trace”. Despite his influence in memory research, many of the terms coined by Semon are used little or infrequently today.'''

'''Donald Hebb, a Canadian Psychologist, has expanded on Semon’s engram theory of memory by producing a guiding hypothesis on the nature of the modification of neuron pathways. He proposed that neurons encoding memory stimuli undergo strengthening of synapses through co-activation with presynaptic cells. Simply put, neurons that “fire together wire together.”  Hebb’s work has been supported by other memory research, specifically that which is done around long term potentiation (LTP) and synaptic plasticity in learning and memory. Other studies suggesting cell-wide altercation, such of Karl S. Lashley, contribute to memory support Hebb’s hypothesis.'''

Karl S. Lashley's search for the engram found that it could not exist in any specific part of the rat's brain, but that memory was widely distributed throughout the cortex.[3] One possible explanation for Lashley's failure to locate the engram is that many types of memory (e.g. visual-spatial, smell, etc.) are used in the processing of complex tasks, such as rats running mazes. The consensus view in neuroscience is that the sorts of memory involved in complex tasks are likely to be distributed among a variety of neural systems, yet certain types of knowledge may be processed and contained in specific regions of the brain.[4] Overall, the mechanisms of memory are poorly understood. Such brain parts as the cerebellum, striatum, cerebral cortex, hippocampus, and amygdala are thought to play an important role in memory. For example, the hippocampus is believed to be involved in spatial and declarative learning, as well as consolidating short-term into long-term memory.

In Lashley's experiments (1929, 1950), rats were trained to run a maze. Tissue was removed from their cerebral cortices before re-introducing them to the maze, to see how their memory was affected. Increasingly, the amount of tissue removed degraded memory, but more remarkably, where the tissue was removed from made no difference.[4]

Later, Richard F. Thompson sought the engram in the cerebellum, rather than the cerebral cortex. He used classical conditioning of the eyelid response in rabbits in search of the engram. He puffed air upon the cornea of the eye and paired it with a tone. (This puff normally causes an automatic blinking response. After a number of experiences associating it with a tone, the rabbits became conditioned to blink when they heard the tone even without a puff.) The experiment monitored several brain regions, trying to locate the engram.

One region that Thompson's group studied was the lateral interpositus nucleus (LIP). When it was deactivated chemically, the rabbits lost the conditioning; when re-activated, they responded again, demonstrating that the LIP is a key element of the engram for this response.[5]

This approach, targeting the cerebellum, though successful, examines only basic, automatic responses, which almost all animals possess, especially as defense mechanisms.

Studies have shown that declarative memories move between the limbic system, deep within the brain, and the outer, cortical regions. These are distinct from the mechanisms of the more primitive cerebellum, which dominates in the blinking response and receives the input of auditory information directly. It does not need to "reach out" to other brain structures for assistance in forming some memories of simple association.

'''Recent studies have been exploring epigenetics within engram memory cells and how this may affect memory. Engrampigenetic is a term that encompasses this relationship, looking specifically at epigenetic modifications occurring in engram memory cells. There is still little known about epigenetic modifications in memory engram cells because the cells are difficult to isolate for epigenetic analysis. '''

'''Despite this setback, methods involving molecular, genetics, and optogenetics have more recently been established to identify engram memory cells. Engram capture strategies allow for transgenic mice to be engineered and used in memory studies. These new methods and strategies have opened the doors of opportunities to observe and modulate engram memory cells.'''

'''The studies around engram memory cells focus on memory issues and how they affect cognition; several focus on Alzheimer’s disease. There is a known association of loss of spines and the onset of Alzheimer’s disease, but scientists are unsure of how the loss affects cognition. '''

An MIT study found that behavior based on high-level cognition, such as the expression of a specific memory, can be generated in a mammal by highly specific physical activation of a specific small subpopulation of brain cells. By reactivating these cells by physical means in mice, such as shining light on neurons affected by optogenetics, a long-term fear-related memory appears to be recalled.[6]

'''This study supports the theory that the loss of dendritic spines on engram memory cells have no effect on the encoding of a memory. The problem lies in the process of retrieving the memory.'''

In 2016, an MIT study found that memory loss in early stages of Alzheimer's disease could be reversed by strengthening specific memory engram cell connections in the brains of Alzheimer mouse models.[7]

'''The findings of this study gave researchers hope in that they show potential for rescuing long-term memory in dementia patients through engram-based strategies. While advances in research are continuing, this possibility is currently limited to patients in the early stages of the disease who have little deterioration of neurons and their connections.'''

Future directions of the study include testing other types of memory and cellular changes that result in strengthened synapses in long term potential.