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An engram is a unit of
cognitive Cognition refers to "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 encoded, stored, and retrieved when needed. It is the retention of information over time for the purpose of influencing future action. If past events could not be remembered, ...
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 an ...
changes in the brain or other biological tissue, 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 Richard Wolfgang Semon (22 August 1859, in Berlin – 27 December 1918, in Munich) was a German zoologist, explorer, evolutionary biologist, a memory researcher who believed in the inheritance of acquired characteristics and applied this to social ...
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 Karl Spencer Lashley (June 7, 1890 – August 7, 1958) was a psychologist and behaviorist remembered for his contributions to the study of learning and memory. A '' Review of General Psychology'' survey, published in 2002, ranked Lashley as the ...
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. The cerebral cortex mostly consists of the six-layered neocortex, with just 10% consisting o ...
. 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 using traditional scientific methods. Later,
Richard F. Thompson Richard Frederick Thompson (September 6, 1930 – September 16, 2014) was an American behavioral neuroscientist. He was the William M. Keck Professor of Psychology and Biological Sciences at the University of Southern California, with a paralle ...
sought the engram in the
cerebellum The cerebellum (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 or even larger. In humans, the cerebe ...
, rather than the cerebral cortex. He used
classical conditioning Classical conditioning (also known as Pavlovian or respondent conditioning) is a behavioral procedure in which a biologically potent stimulus (e.g. food) is paired with a previously neutral stimulus (e.g. a triangle). It also refers to the lear ...
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. 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 Thompson's group studied was the lateral interpositus nucleus (LIP). When it 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 (word meanings, concepts, facts, and ideas) is intertwined in experience and dependent on culture. We can learn abou ...
.


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 (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 or even larger. In humans, the cerebe ...
,
striatum The striatum, or corpus striatum (also called the striate nucleus), is a nucleus (a cluster of neurons) in the subcortical basal ganglia of the forebrain. The striatum is a critical component of the motor and reward systems; receives gluta ...
,
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. The cerebral cortex mostly consists of the six-layered neocortex, with just 10% consisting o ...
,
hippocampus The hippocampus (via Latin from Greek , 'seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic syste ...
, and
amygdala The amygdala (; plural: amygdalae or amygdalas; also '; Latin from Greek, , ', 'almond', 'tonsil') is one of two almond-shaped clusters of nuclei located deep and medially within the temporal lobes of the brain's cerebrum in complex ver ...
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 human memory, the other of which is implicit memory. Explicit memory is the conscious, intentional recollection of factual information, previous experiences, and c ...
, as well as consolidating short-term into long-term memory. 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. 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 expression of light-sensitive ion channels, pumps or enzymes specifically in the target cells. On the level of individ ...
, 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 expression of light-sensitive ion channels, pumps or enzymes specifically in the target cells. On the level of individ ...
and
chemogenetics Chemogenetics is the process by which macromolecules can be engineered to interact with previously unrecognized small molecules. Chemogenetics as a term was originally coined to describe the observed effects of mutations on chalcone isomerase activ ...
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 several other names, is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with G protein-cou ...
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 that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As ...
could be reversed by strengthening specific memory engram cell connections in the brains of Alzheimer mouse models.


See also

* Multiple trace theory * Samskara


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