essay on memory formation

An official website of the United States government

The .gov means it’s official. Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

• Publications
• Account settings

Preview improvements coming to the PMC website in October 2024. Learn More or Try it out now .

• Advanced Search
• Journal List
• Ind Psychiatry J
• v.30(Suppl 1); 2021 Oct

Memory: Neurobiological mechanisms and assessment

Swaleha mujawar.

Department of Psychiatry, Regional Mental Hospital, Nagpur, Maharashtra, India

Jaideep Patil

1 Department of Psychiatry, Dr. D. Y. Patil Medical College, Hospital and Research Center, Dr D Y Patil Vidyapeeth, Pune, Maharashtra, India

Bhushan Chaudhari

Daniel saldanha.

Memory is the process of retaining of knowledge over a period for the function of affecting future actions. It can be divided into declarative and procedural types. The process of memory consolidation is done in the hippocampus. The long-term memories are spread among various areas of the cerebrum depending on the different perceptual properties. The process of long-term potentiation and molecular changes occurring during memory formation are discussed in detail below. The steps involved in memory formation include encoding, storage, and recall (retrieval) in that order. Amnesia is a phenomenon in which there is the problem in memory formation which can be due to trauma to the brain, certain diseases, or stressors. While the assessment of memory has greatly improved, we are only beginning to understand the underlying mechanisms.

Memory is the process of retaining of knowledge over a period for the function of affecting future actions.[ 1 ] From a historical standpoint, the area of memory research from 1870 to 1920 was focused mainly on human memory.[ 2 ] The book: The Principles of Psychology written by famous psychologist William James suggested that there is a difference between memory and habit.[ 3 ] The case of Henry Molaison was first described as a result of research of two main researchers, namely William Beecher Scoville and Brenda Milner.[ 4 ] The findings have contributed a lot to our understanding of memory. Since then, a lot of research has been done in the field of memory and led to many advancements. The Nobel Prize in Physiology or Medicine in the year 2000 was given to Eric Richard Kandel for his contribution in understanding the physiological basis of memory storage in neurons. The prize was shared with Arvid Carlsson and Paul Greengard.

CLASSIFICATION OF MEMORY

Memory was classified into two types-declarative (explicit) and procedural (implicit) memories by Anderson.[ 5 ] Explicit memory can be defined as the information regarding places, things, people, and events, etc., It can be recollected by conscious effort. It is stored in the medial part of the temporal lobe of the cerebrum and hippocampus. It may be subdivided into episodic memory which is also called autobiographic memory and semantic memory. Episodic memory recalls remember personal events and experiences. Whereas semantic memory recalls facts which can be general or autobiographical. Since Implicit memory is recollected unconsciously it is called nondeclarative. It is stored in various regions of the brain like the cerebellum, the neocortex, the striatum, the amygdala, etc.

NEUROBIOLOGY

Research suggests that the hippocampus plays an important role in memory consolidation. It was proved by experiments, wherein lesions were applied to rat hippocampi at various times after learning.[ 5 ] Looking from the molecular and cellular point of view two proteins involved are calcium calmodulin-dependent protein kinase II (CaMKII)[ 6 , 7 ] and protein phosphatase 1 (PP1). During the formation of memory, there is Ca2 + influx after which CaMKII goes through autophosphorylation process which changes it into an activated kinase. Since PP1 has an inhibitory effect on memory it returns the CaMKII to its resting state. This opposite relationship involving CaMKII and PP1 characterizes a push-pull system actually has an important part in memory formation. Hence, a balance maintained between remembering and forgetting the memories which are stored. Consolidation of short-term memories however requires a functional change after which gene transcription and protein synthesis should occur.

During any learning process, persistent stimulation causes sustained activation of two pathways namely the protein kinase A (PKA) and MAP kinase Erk (MAPK) pathways. PKA causes phosphorylation as well as the activation of CREB1a which is a transcriptional activator, whereas MAPK causes phosphorylation and inactivation of CREB2, a transcriptional repressor.

The most unique characteristic of our brain is the facility to acclimatize to the ever-changing surroundings and to increase its functioning by learning through experience. Learning and memory formation involves a remarkably interesting phenomena of neuroplasticity. During learning there occurs a structural change at the synapse which includes a change in the power of old synapses and changes in the quantity of synaptic connections in particular pathways. Synaptic associations that are less used become weaker over a period and ultimately perish. The ones which are used a lot become stronger with each use and in due course boost in number. Studies suggest that long-term memory (LTM) storage may be preserved by DNA methylation or prions.[ 8 , 9 ]

MULTI-STORE MODEL OF MEMORY

Richard Atkinson and Richard Shiffrin put forth a model of memory which is known as “The multi-store model or modal model.”[ 10 ] It states that memory consists of three distinct elements: “a sensory register, a short-term store, and a long-term store.” The data from the environment and our senses goes into the memory via the sensory register. The short-term store, otherwise known as working memory or short-term memory (STM), receives and holds input from both the sensory register and the long-term store. Finally, if the information is rehearsed in the short-term store then it goes in the long-term store, wherein it is held indefinitely. Memory consists of the following steps-encoding, storage, and recall (retrieval). Encoding is the process of altering the material reaching our nervous system into a mode that the system can manage so that it can be easily stored. There are various methods through which knowledge can be encoded is via visual, acoustic, semantic coding. The STM is encoded mainly via acoustic coding. The LTM however usually involves semantic coding. Nonetheless, data in LTM can also be encoded both via visual and acoustic coding. When it comes to acquiring data out of storage, the process of retrieval comes into the picture. Unable to remember information can be due to the inability to retrieve that piece of information. Retrieval helps us understand the dissimilarities among STM and LTM. STM is stored and retrieved chronologically. The storage and retrieved of LTM on the other hand occur via association. Thus, the organization of information can facilitate the process of retrieval.

Sensory memory consists of three types. The first is the iconic memory. It is a quickly declining storage of visual data. It stores an image for a small duration which has been perceived by the person briefly. The second is the echoic memory. It is described as storage of sounds for short durations that have been heard briefly.[ 3 ] Moreover, haptic memory characterizes a database for touch stimuli.[ 11 ]

WORKING MEMORY MODEL

The “working memory model” was put forward by Baddeley and Hitch. According to them, working memory comprises the following: “the central executive, the phonological loop, and the visuospatial sketchpad” along with a multimodal episodic buffer.[ 12 ]

Working memory and STM are often used interchangeably. In his paper, “the magical number 7 ± 2,” George A. Miller proved that the store of STM was 7 ± 2 items. However, contemporary approximations of the capability of STM are lesser, characteristically of the order of 4–5 items.[ 13 ] Nonetheless, this can be augmented using a method called chunking.[ 14 ] A few health behaviors like exercise can prevent forgetting from happening.[ 15 ]

Forgetting was classified under various types by Paul Connerton: They are-prescriptive forgetting, planned obsolescence, formation of the new identity, repressive erasure, structural amnesia, annulment, and humiliated silence.[ 16 ]

Retroactive interference can be defined as the phenomenon when new information or memories disturb the old information. Whereas proactive interference happens when old information disturbs the retrieval of new memories.[ 17 ] Trace decay elucidates memories that are stored in STM and LTM with the assumption that memories leave a trace in the central nervous system. Herman Ebbinghaus in 1913 proposed a forgetting curve. It theorizes the deterioration of memory retention over a period. It represents a curve showing how memory is lost over a period if there is no effort to preserve it.

Amnesia is a phenomenon in which there is the problem in memory formation which can be due to trauma to the brain, certain diseases, or stressors.[ 18 ] It can be subdivided into retrograde amnesia and anterograde amnesia.

Retrograde amnesia is the lack of ability to recover information that was attained before a specific time, typically before an accident or surgery.[ 19 ] Anterograde amnesia is the lack of ability to allocate new information from the short-term to the long-term store. It is observed that suffering from extended periods of amnesia after a trauma can be a prognostic indicator and that the improvement from the symptoms of concussion may take more than usual.[ 20 ]

A scale consisting of 30 questions which is employed to gauge impairment inmemory is the Mini-Mental State Examination.[ 21 ] Another scale employed for detecting mild and early memory problems is the Montreal Cognitive Assessment.[ 22 ] Also utilized to detect memory issues is Addenbrooke's Cognitive Examination.[ 23 ] A scale consisting of 50 questions is the test of memory malingering. It is a visual memory recollection test that differentiates between true memory impairment and malingering. It has two learning trials and a retention trial after a delay which is optional.[ 24 ] The Wechsler Memory Scale segregates clinical categories. It can differentiate between the various clinical categories.[ 25 ]

Advances in knowledge have resulted in the realization that memory is a very complex system. While the assessment of memory has greatly improved, we are only beginning to understand the underlying mechanisms.

Financial support and sponsorship

Conflicts of interest.

There are no conflicts of interest.

Featured Topics

Featured series.

A series of random questions answered by Harvard experts.

Explore the Gazette

Read the latest.

Lifting a few with my chatbot

Hate mosquitoes? Who doesn’t? But maybe we shouldn’t.

‘Harvard Thinking’: Climate alignment is no easy task

Making memories.

Kevin Jiang

HMS Communications

Study sheds light on how neurons form long-term memories

On a late summer day in 1953, a young man who would soon be known as patient H.M. underwent experimental surgery. In an attempt to treat his debilitating seizures, a surgeon removed portions of his brain, including part of a structure called the hippocampus. The seizures stopped.

Unfortunately, for patient H.M., so too did time. When he woke up after surgery, he could no longer form new long-term memories, despite retaining normal cognitive abilities, language and short-term working memory. Patient H.M.’s condition ultimately revealed that the brain’s ability to create long-term memories is a distinct process that depends on the hippocampus.

Scientists had discovered where memories are made. But  how  they are made remained unknown.

Now, neuroscientists at Harvard Medical School (HMS) have taken a decisive step in the quest to understand the biology of long-term memory and find ways to intervene when memory deficits occur with age or disease.

Reporting in  Nature  on Dec. 9, they describe a newly identified mechanism that neurons in the adult mouse hippocampus use to regulate signals they receive from other neurons, in a process that appears critical for memory consolidation and recall.

The study was led by  Lynn Yap , HMS graduate student in neurobiology, and  Michael Greenberg , chair of neurobiology in the Blavatnik Institute at HMS.

“If we can better understand this process, we will have new handles on memory and how to intervene when things go wrong, …” Michael Greenberg, Blavatnik Institute at HMS

“Memory is essential to all aspects of human existence. The question of how we encode memories that last a lifetime is a fundamental one, and our study gets to the very heart of this phenomenon,” said Greenberg, the HMS Nathan Marsh Pusey Professor of Neurobiology and study corresponding author.

The researchers observed that new experiences activate sparse populations of neurons in the hippocampus that express two genes, Fos and Scg2. These genes allow neurons to fine-tune inputs from so-called inhibitory interneurons, cells that dampen neuronal excitation. In this way, small groups of disparate neurons may form persistent networks with coordinated activity in response to an experience.

“This mechanism likely allows neurons to better talk to each other so that the next time a memory needs to be recalled, the neurons fire more synchronously,” Yap said. “We think coincident activation of this Fos-mediated circuit is potentially a necessary feature for memory consolidation, for example, during sleep, and also memory recall in the brain.”

Circuit orchestration

In order to form memories, the brain must somehow wire an experience into neurons so that when these neurons are reactivated, the initial experience can be recalled. In their study, Greenberg, Yap and team set out to explore this process by looking at the gene Fos.

First  described  in neuronal cells by Greenberg and colleagues in 1986, Fos is expressed within minutes after a neuron is activated. Scientists have taken advantage of this property, using Fos as a marker of recent neuronal activity to identify brain cells that regulate thirst,  torpor , and many other behaviors.

Scientists hypothesized that Fos might play a critical role in learning and memory, but for decades, the precise function of the gene has remained a mystery.

To investigate, the researchers exposed mice to new environments and looked at pyramidal neurons, the principal cells of the hippocampus. They found that relatively sparse populations of neurons expressed Fos after exposure to a new experience. Next, they prevented these neurons from expressing Fos, using a virus-based tool delivered to a specific area of the hippocampus, which left other cells unaffected.

Mice that had Fos blocked in this manner showed significant memory deficits when assessed in a maze that required them to recall spatial details, indicating that the gene plays a critical role in memory formation.

The researchers studied the differences between neurons that expressed Fos and those that did not. Using  optogenetics  to turn inputs from different nearby neurons on or off, they discovered that the activity of Fos-expressing neurons was most strongly affected by two types of interneurons.

Neurons expressing Fos were found to receive increased activity-dampening, or inhibitory, signals from one distinct type of interneuron and decreased inhibitory signals from another type. These signaling patterns disappeared in neurons with blocked Fos expression.

“What’s critical about these interneurons is that they can regulate when and how much individual Fos-activated neurons fire, and also when they fire relative to other neurons in the circuit,” Yap said. “We think that at long last we have a handle on how Fos may in fact support memory processes, specifically by orchestrating this type of circuit plasticity in the hippocampus.”

Imagine the day

The researchers further probed the function of Fos, which codes for a transcription factor protein that regulates other genes. They used single-cell sequencing and additional genomic screens to identify genes activated by Fos and found that one gene in particular, Scg2, played a critical role in regulating inhibitory signals.

In mice with experimentally silenced Scg2, Fos-activated neurons in the hippocampus displayed a defect in signaling from both types of interneurons. These mice also had defects in theta and gamma rhythms, brain properties thought to be critical features of learning and memory.

Previous studies had shown that Scg2 codes for a neuropeptide protein that can be cleaved into four distinct forms, which are then secreted. In the current study, Yap and colleagues discovered that neurons appear to use these neuropeptides to fine-tune inputs they receive from interneurons.

Together, the team’s experiments suggest that after a new experience, a small group of neurons simultaneously express Fos, activating Scg2 and its derived neuropeptides, in order to establish a coordinated network with its activity regulated by interneurons.

“When neurons are activated in the hippocampus after a new experience, they aren’t necessarily linked together in any particular way in advance,” Greenberg said. “But interneurons have very broad axonal arbors, meaning they can connect with and signal to many cells at once. This may be how a sparse group of neurons can be linked together to ultimately encode a memory.”

The study findings represent a possible molecular- and circuit-level mechanism for long-term memory. They shed new light on the fundamental biology of memory formation and have broad implications for diseases of memory dysfunction.

The researchers note, however, that while the results are an important step in our understanding of the inner workings of memory, numerous unanswered questions about the newly identified mechanisms remain.

“We’re not quite at the answer yet, but we can now see many of the next steps that need to be taken,” Greenberg said. “If we can better understand this process, we will have new handles on memory and how to intervene when things go wrong, whether in age-related memory loss or neurodegenerative disorders such as Alzheimer’s disease.”

The findings also represent the culmination of decades of research, even as they open new avenues of study that will likely take decades more to explore, Greenberg added.

“I arrived at Harvard in 1986, just as my paper describing the discovery that neuronal activity can turn on genes was published,” he said. “Since that time, I’ve been imagining the day when we would figure out how genes like Fos might contribute to long-term memory.”

Additional authors include Noah Pettit, Christopher Davis, M. Aurel Nagy, David Harmin, Emily Golden, Onur Dagliyan, Cindy Lin, Stephanie Rudolph, Nikhil Sharma, Eric Griffith, and Christopher Harvey.

The study was supported by the National Institutes of Health (grants R01NS028829, R01NS115965, R01NS089521, T32NS007473 and F32NS112455), a Stuart H.Q. and Victoria Quan fellowship, a Harvard Department of Neurobiology graduate fellowship, an Aramont Fund.

Share this article

You might like.

Sociologist Sherry Turkle warns against growing trend of turning to AI for companionship, counsel

Entomologist says there is much scientists don’t know about habitats, habits, impacts on their environments

Experts at the Salata Institute outline tensions between global and local priorities

College accepts 1,937 to Class of 2028

Students represent 94 countries, all 50 states

Pushing back on DEI ‘orthodoxy’

Panelists support diversity efforts but worry that current model is too narrow, denying institutions the benefit of other voices, ideas

So what exactly makes Taylor Swift so great?

Experts weigh in on pop superstar's cultural and financial impact as her tours and albums continue to break records.