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An engram is a unit of
cognitive Cognition is the "mental action or process of acquiring knowledge and understanding through thought, experience, and the senses". It encompasses all aspects of intellectual functions and processes such as: perception, attention, thought, ...
information imprinted in a physical substance, theorized to be the means by which
memories Memory is the faculty of the mind by which data or information is Encoding (memory), encoded, stored, and retrieved when needed. It is the retention of information over time for the purpose of influencing future Action (philosophy), action. I ...
are stored as biophysical or
biochemical Biochemistry, or biological chemistry, is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology, ...
changes in the brain or other
biological tissue In biology, tissue is an assembly of similar cells and their extracellular matrix from the same embryonic origin that together carry out a specific function. Tissues occupy a biological organizational level between cells and a complete or ...
, in response to external stimuli. Demonstrating the existence of, and the exact mechanism and location of, neurologically defined engrams has been a focus of persistent research for many decades.


History

The term "engram" was coined by memory researcher Richard Semon in reference to the physical substrate of memory in the organism. Semon warned, however: "In animals, during the evolutionary process, one organic system—the nervous system—has become specialised for the reception and transmission of stimuli. No monopoly of this function by the nervous system, however, can be deduced from this specialisation, not even in its highest state of evolution, as in Man." One of the first ventures on identifying the location of a memory in the brain was undertaken by Karl S. Lashley who removed portions of the brain in rodents. In Lashley's experiments, rats were trained to run through a maze and then tissue was removed from their
cerebral cortex The cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. It is the largest site of Neuron, neural integration in the central nervous system, and plays ...
. Increasing the amount of tissue removed increased the degradation of memory, but more remarkably, ''where'' the tissue was removed from made no difference. His search thus proved unsuccessful, and his conclusion – that memory is diffusely distributed in the brain – became widely influential. However, today we appreciate that memory is not completely but only ''largely'' distributed in the brain; this, together with its dynamic nature, makes engrams challenging to identify, or prove that they exist, using traditional scientific methods. Later, David A. McCormick and Richard F. Thompson sought the engram in the
cerebellum The cerebellum (: cerebella or cerebellums; Latin for 'little brain') is a major feature of the hindbrain of all vertebrates. Although usually smaller than the cerebrum, in some animals such as the mormyrid fishes it may be as large as it or eve ...
, rather than the cerebral cortex. They used
classical conditioning Classical conditioning (also respondent conditioning and Pavlovian conditioning) is a behavioral procedure in which a biologically potent Stimulus (physiology), stimulus (e.g. food, a puff of air on the eye, a potential rival) is paired with a n ...
of the eyelid response in rabbits in search of the engram. They puffed air upon the cornea of the eye and paired it with a tone. 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. One region that David A. McCormick studied was the lateral interpositus nucleus (LIP). He found that recordings of neurons in this nucleus revealed activity that mirrored the learning, stimulation of the nucleus elicited the learned response, and lesion of this brain region abolished the response. Other members of the Thompson group found that when the interpositus nucleus was deactivated chemically, the conditioned response disappeared; when re-activated, they responded again, demonstrating that the LIP is a key element of the engram for this response. This approach, targeting the cerebellum, though successful, examines only basic, automatic responses, which virtually all animals possess. However, engrams of specific types of memory are found in the subsystems mediating that learning process and as such solely engrams of simple conditioning are associated with the LIP but not, for instance, engrams of
semantic memory Semantic memory refers to general world knowledge that humans have accumulated throughout their lives. This general knowledge (Semantics, word meanings, concepts, facts, and ideas) is intertwined in experience and dependent on culture. New concep ...
.


Overview

Neuroscience acknowledges the existence of many types of memory and their physical location within the brain is likely to be dependent on the respective system mediating the encoding of this memory.Gerrig and Zimbardo (2005) ''Psychology and Life'' (17th edition: International edition) Such brain parts as the
cerebellum The cerebellum (: cerebella or cerebellums; Latin for 'little brain') is a major feature of the hindbrain of all vertebrates. Although usually smaller than the cerebrum, in some animals such as the mormyrid fishes it may be as large as it or eve ...
,
striatum The striatum (: striata) or corpus striatum is a cluster of interconnected nuclei that make up the largest structure of the subcortical basal ganglia. The striatum is a critical component of the motor and reward systems; receives glutamat ...
,
cerebral cortex The cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. It is the largest site of Neuron, neural integration in the central nervous system, and plays ...
,
hippocampus The hippocampus (: hippocampi; via Latin from Ancient Greek, Greek , 'seahorse'), also hippocampus proper, is a major component of the brain of humans and many other vertebrates. In the human brain the hippocampus, the dentate gyrus, and the ...
, and
amygdala The amygdala (; : amygdalae or amygdalas; also '; Latin from Greek language, Greek, , ', 'almond', 'tonsil') is a paired nucleus (neuroanatomy), nuclear complex present in the Cerebral hemisphere, cerebral hemispheres of vertebrates. It is c ...
are thought to play an important role in memory. For example, the hippocampus is believed to be involved in spatial and
declarative memory Explicit memory (or declarative memory) is one of the two main types of Long-term memory, long-term human memory, the other of which is implicit memory. Explicit memory is the Consciousness, conscious, intentional Recall (memory), recollection of f ...
, as well as consolidating short-term into long-term memory. Studies have shown that declarative memories move between the
limbic system The limbic system, also known as the paleomammalian cortex, is a set of brain structures located on both sides of the thalamus, immediately beneath the medial temporal lobe of the cerebrum primarily in the forebrain.Schacter, Daniel L. 2012. ''P ...
, 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. 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 Optogenetics is a biological technique to control the activity of neurons or other cell types with light. This is achieved by Gene expression, expression of Channelrhodopsin, light-sensitive ion channels, Halorhodopsin, pumps or Photoactivated ade ...
, a long-term fear-related memory appears to be recalled. Another study used
optogenetics Optogenetics is a biological technique to control the activity of neurons or other cell types with light. This is achieved by Gene expression, expression of Channelrhodopsin, light-sensitive ion channels, Halorhodopsin, pumps or Photoactivated ade ...
and chemogenetics to control neuronal activity in animals encoding and recalling the memory of a spatial context to investigate how the brain determines the lifetime of memories. The results found by the researchers have defined a role for specific hippocampal inhibitory cells (
somatostatin Somatostatin, also known as growth hormone-inhibiting hormone (GHIH) or by #Nomenclature, several other names, is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with G ...
expressing cells) in restricting the number of neurons involved in the storage of spatial information and limiting the duration of the associated memory. In 2016, an MIT study found that memory loss in early stages of
Alzheimer's disease Alzheimer's disease (AD) is a neurodegenerative disease and the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems wit ...
could be reversed by strengthening specific memory engram cell connections in the brains of Alzheimer mouse models.


See also

*
Multiple trace theory In psychology, multiple trace theory is a memory consolidation model advanced as an alternative model to Recognition memory, strength theory. It posits that each time some information is presented to a person, it is Neural coding, neurally encoded ...
* Samskara * TetTag mice, used for memory recall by optogenetic stimulation


References


Further reading

* ''Forgotten Ideas, Neglected Pioneers: Richard Semon and the Story of Memory'', Daniel Schacter, 2001 * * Gonzalez, Robbie (July 25, 2013)
Memory implantation is now officially real
Gizmodo. Retrieved December 3, 2021. * {{Authority control Memory Neuropsychology