How is the beginning of an episodic memory encoded in the brain?

How is the beginning of an episodic memory encoded in the brain?

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before asking how information is stored, I need to understand

  1. how does episode start and end are determined by the brain ?
  2. how do i remember a movie ?

can you suggest a link to article addressing this issue


We don't have a full understanding of how episodic recall really happens in the brain, but there are theoretical approaches to understanding memory that are supported (but not shown definitively - it is really difficult to design appropriate experiments that are not beyond current technological capabilities) by experimental evidence. These approaches don't require any sort of hard "start" or "end" signal for episodic memory to work. In these approaches, an episodic memory is thought of as a sequence of brain states that correspond to previously experienced states.

The sequence occurs because connectivity promotes the network to progress from State A to State B to State C, etc. Additionally, all of the states consisting of that one "connected" memory are also associated, so that they prime one another.

To recall, you don't need to start at State A - you can start anywhere in the chain, and just recalling State C will prime you to also recall State A and B, so you can mentally "rewind" the memory a bit (we have no idea how exactly this type of conscious control works), even though it progresses most clearly in the A->B->C sequence.

The point of entry that allows you to initially get in to this chain might not be part of that episodic memory, either. For example, maybe you see a cat, and this leads to to an episodic memory of one event you shared with your own cat 5 years ago.

Brains are very dynamic, they do not behave like a feed-forward computation you might implement in a simple computer program. It is possible that there are "start" or "end" signals for episodic memories that we haven't found yet, but they may not be necessary at all.

For some further reading you could look for references on attractor networks, pattern separation and pattern completion, and theories of memory formation.

The book by Dayan and Abbott on theoretical neuroscience is also a good approach to some of the more basic background and includes an introduction to biologically-inspired models of learning and memory.

How is the beginning of an episodic memory encoded in the brain? - Biology

There are multiple types of memory:

  1. Episodic: Episodic memories are what most people think of as memory and include information about recent or past events and experiences, such as where you parked your car this morning or the dinner you had with a friend last month. The recollection of experiences is contingent on three steps of memory processing: encoding, consolidation/storage and retrieval. The hippocampus and surrounding structures in the temporal lobe are important in episodic memory and are part of an important network called the default mode network, which includes several brain areas including frontal and parietal regions and has been implicated in episodic memory functioning.
  2. Semantic: Semantic memory refers to your general knowledge including knowledge of facts. For example, your knowledge of what a car is and how an engine works are examples of semantic memory.
  3. Remote: The memory of events that occurred in the distant past is a type of episodic memory referred to as remote or long term memory. The underlying anatomy of remote memory is poorly understood, in part because testing this type of memory must be personalized to a patient’s autobiographical past. What is known is that, like semantic memory, remote memory eventually becomes independent of the hippocampus and appears to be “stored” more broadly in the neocortex. Likely because of this unique neuroanatomy, remote episodic memories do not tend to be as severely disrupted as recent episodic memories in neurodegenerative diseases (e.g., Alzheimer’s disease).
  4. Working: Working memory is used to describe the process where one “holds on” and manipulates to small bits of current information in mind, like a telephone number. Though commonly referred to as short term memory, working memory is actually more closely related to attention and falls under the domain of executivefunction. The capacity of our working memory is limited, allowing us to keep only a few bits of information in mind at one time. Working memory involves the frontal cortex and parietal lobe.

Each type uses a different network in the brain, and therefore, one type can be affected by disease or injury while another type functions normally.

Another dimension

When the cognitive neuroscientist Endel Tulving coined the term “episodic memory” in a book chapter in 1972, he observed that recalling the content of memories was linked to a strong subjective sense of where and when an episode took place. The where component has been a focus of neuroscientific research for decades. In 1971, University of College London neuroscientist John O’Keefe discovered place cells, neurons in the hippocampus that fire in response to an animal being in specific locations. He shared the Nobel Prize in Physiology or Medicine with the Mosers in 2014 for their discovery of grid cells in the MEC, and several studies published since suggest that grid cells help the hippocampus generate place cells during memory formation.

How the brain encodes the when of memories has received far less attention, notes Andy Lee, a cognitive neuroscientist at the University of Toronto. “Space is something we see, it’s easy to manipulate. . . . It’s somewhat easier for us to grasp intuitively,” he says. “Time is much harder to study.”

Despite the thorniness of the subject, researchers have established in the last decade or so “that the brain has multiple ways to tell time,” says Dean Buonomano, a behavioral neuroscientist at the University of California, Los Angeles, and author of the 2017 book Your Brain is a Time Machine. Time is integral to many biological phenomena, from circadian rhythms to speech perception to motor control or any other task involving prediction, Buonomano adds.

One of the biggest breakthroughs in understanding time as it relates to episodic memory came a few years after Tsao completed his internship, when the late Boston University neuroscientist Howard Eichenbaum and colleagues published evidence of “time cells” in the hippocampus of rats. Hints of time-sensitive cells in the hippocampus had been trickling out of labs for a couple of years, but Eichenbaum’s study showed definitively that certain cells fire in sequence at specific timepoints during behavioral tasks: a rat trained to associate a stimulus with a subsequent reward would have one hippocampal neuron that peaked in activity a couple hundred milliseconds after the stimulus was presented, another that peaked in activity a few hundred milliseconds after that, and so on—as if the hippocampus were somehow marking the passage of time.

The findings, which are beginning to be extended to humans thanks to work by Lee’s group and a separate team at the University of Texas Southwestern, among others, generated interest in the representation of time alongside space in episodic memories. Yet it was unclear what was telling these cells when to fire, or what role, if any, they played in the representation of time passing within and between individual episodic memories. For Marc Howard, long fascinated by questions about the physical nature of time and the brain’s perception of it, the puzzle was a captivating one.

In the years leading up to Eichenbaum’s paper, Howard and his postdoc Karthik Shankar had been developing a mathematical model based on the idea that the brain could create a proxy for the passage of time using a population of “temporal context cells” that gradually changes its activity. According to this model, all neurons in this population become active following some input (a sensory stimulus, for example), and then relax, one by one, creating a gradually decaying signal that is unique from moment to moment. Then, during memory formation, the brain converts this signal into a series of sequentially firing “timing cells,” which log moments within a memory. The same framework could also work to tag entire episodes according to the order in which they took place.

The specific mathematical details of the model—in particular, the use of an operation called a Laplace transform to describe how temporal context cells compute time, and the inversion of that transform to describe the behavior of the hypothesized timing cells—nicely recapitulated several known features of episodic memory, such as the fact that it’s easier to remember things that happened more recently than things that happened a long time ago. And after hippocampal time cells, with their sequential firing patterns, were described in 2011, Howard, by then at Boston University, was gratified to see that they seemed to possess many of the properties he and Shankar had predicted for their so-called timing cells.

But the first piece of the puzzle was still missing. No one had identified the gradually evolving set of temporal context neurons needed to produce the time signal in the first place, Howard says. “We waited a long time for somebody to do the experiment—really just moving the electrodes over to the LEC and looking for it.”

Sleep for preserving and transforming episodic memory

Sleep is known to support memory consolidation. Here we review evidence for an active system consolidation occurring during sleep. At the beginning of this process is sleep's ability to preserve episodic experiences preferentially encoded in hippocampal networks. Repeated neuronal reactivation of these representations during slow-wave sleep transforms episodic representations into long-term memories, redistributes them toward extrahippocampal networks, and qualitatively changes them to decontextualized schema-like representations. Electroencephalographic (EEG) oscillations regulate the underlying communication: Hippocampal sharp-wave ripples coalescing with thalamic spindles mediate the bottom-up transfer of reactivated memory information to extrahippocampal regions. Neocortical slow oscillations exert a supraordinate top-down control to synchronize hippocampal reactivations of specific memories to their excitable up-phase, thus allowing plastic changes in extrahippocampal regions. We propose that reactivations during sleep are a general mechanism underlying the abstraction of temporally stable invariants from a flow of input that is solely structured in time, thus representing a basic mechanism of memory formation.

Episodic memory

Author Note: Steven Lee Douglas, Iveta Rukere, Teather Smith, Lenka Valentine, Department of Psychology, Shepherd University

Correspondence concerning this article should be addressed to Steven Lee Douglas, Iveta Rukere, Teather Smith, Lenka Valentine, Department of Psychology, Shepherd University, Shepherdstown, West Virginia 25443.


In 1957, Scoville and Milner wrote a paper on “HM” who at the age of 27 years old had major brain surgery where doctors removed portions of his brain in an attempt to relieve serious seizures he suffered due to his epilepsy. According to the reports, surgery was successful in reducing the number of seizures he was having to the level that they could treat his remaining seizures with medication. What makes the case of “HM” so well known is that by removing the parts of the brain that included the hippocampus, he was no longer capable of storing short term memories. He was able to remember long term memories (LTM) from before his surgery but could no longer retain short term memory (STM). He was able to retain semantic memories (Baddeley, 1966) but could no longer record episodic memory (Tulving, 1972). In 1994 Tulving wrote about “KC” a young Canadian who in a serious motor accident damaged his temporal lobe. He lost all of his episodic memory. He was able to remember places but not what happened in those locations.

In 1977, Brown and Kulik, published research on Flashbulb Memory. They researched how well subjects could remember the assassination of President John F Kennedy in 1993. They determined that subjects had a stronger ability to remember details around where they were and what they were doing when they heard the news that the President was dead. They were not able to remember great details about what they were doing the day before. Neisser (1982) challenged earlier findings with questioning where people were when Pearl Harbor was attacked. His own memory recalled that he was at a baseball game at the time. This however is not possible since baseball season is over before December 8 th . He could remember elements of news reports of the attack but not where he was at the time. Additional studies have been done on Flashbulb Memory using the Challenger explosion (McCloskey, Wible, and Cohen, 1988 Neisser and Harsch, 1992) and the terrorist attacks on 9/11 (Talarico and Rubin, 2003). In all of these studies, subjects were able to retain a great deal of information regarding the actual events but were not able to remember perfect details on what they were doing or where they were at the time. Another interesting factor that played a role in making proper retrieval possible is referred to as Confabulation (Wade & Tavris, 2011). The “Conditions of Confabulation” tell that a memory of an event can be influenced by other people’s memories that someone had overheard over time. In the case referred to here, a family member heard the same story so many times about someone else in the family knocking down a wall that they eventually believed that they had actually been there, when in fact they were not.

A person’s ability to pull from their Long Term Memory depends on how the memory was stored in the beginning. A method of memory retrieval was developed called “Material-induced Organization (Bower, Clark, Lesgold and Winzenz,, 1969) where common associations are used to enhance our memory. In a research experiment they determined that when grouping words together that had apparent relationships (i.e. boy/girl orange/fruit) the subjects were able to recall 100% of 112 words after 4 sets of study and recall. They were allowed to study the words for 1 minute and then given 5 minutes to recall them. After 4 attempts they were able to recall 100% of the words. In a second control group they used word groups that held little obvious relationship. At the end of the 4 sets of study and recall, this group was not able to achieve higher than 60% recall. The more pieces available that are associated with an original memory the more reliable that memory will be.

The Power of Suggestion

To show how easily memory can be tainted, Lotus, Miller and Burns (1978) conducted a visual experiment with 30 slides depicting a Datsun car going through a stop sign (a 2 nd control group saw as yield sign) and hitting a pedestrian. In questioning the participants as to what they could recall, suggestions were made in the questions in an attempt to mislead and distort their memory. By asking the control group that saw a stop sign, “When the car went through the yield sign, did it hit the pedestrian?” as many as 59% failed to answer correctly and could not recall the stop sign and replaced the memory with the suggestion made in the question.

In a study by Ceci and Bruck (1995), they found that the younger a child is the easier it is to change what they believe by using suggestive leading questions. In their research in a courtroom setting they found that it is possible to repeatedly suggest something has happened to a child and eventually the child will believe the suggestion was real. To what degree they are able to understand what they recall from the false information depends on their age. Studies found that the older the children are the less likely they will accept the false memories as their own. In a study by Poole and Lamb (1998) a little girl thought her privates referred to her elbows when the induced memory was regarding a visiting adult having touched children inappropriately.

Working memory (WM) provides temporary storage and manipulation of information that is necessary for cognition. Even though working memory has limited capacity at any given time, it has immense memory content in the sense that it acts on the brain’s nearly unlimited inventory of lifetime long-term memories. Using simulations, it has been shown that large memory content and functionality of working memory emerge spontaneously if the spike-timing nature of neuronal processing is taken into account. At this point, memories are represented by extensively overlapping groups of neurons that exhibit stereotypical time-locked spatiotemporal spike-timing patterns. These patterns are called polychromous patterns, and synapses that are forming polychromous neuronal groups (PNGs) are subject to associative synaptic plasticity in the form of both long-term and short-term spike-timing dependent plasticity. While long-term increased effectiveness is essential in PNG formation, short-term plasticity can temporarily strengthen the synapses of selected PNGs and lead to an increase in the spontaneous reactivation rate of these PNGs. This increased reactivation rate results in high interspike interval variability and irregular, yet systematically changing, elevated firing rate profiles within the neurons of the selected PNGs. (Szatmáry & Izhikevich, 2010)

Long Term Memory and Sleep Connection

Scientists in Germany conducted a research that examined the possible role of sleep in converting new experiences to longterm memory. Volunteers were placed in a rose-scented room where they played a computer version of a card game Memory. They had to remember locations of paired cards that were flashed on the screen for a few seconds. Later, while they were sleeping, researchers exposed the volunteers to rose fragrance, because odors can trigger memories. Volunteers performed better at the game when exposed to the scent during slow-wave sleep, and the brain imaging during slow-wave sleep showed that the scent cue activated the hippocampus, which is a region linked with memory (Choi, 2007).

Biology of Memory

The biology of memory refers to the biological changes that occur to the brain as memories are created. Memories fall into two categories: long-term and short-term. Biological changes occur in the brain each time a memory is created, however those changes are different depending on the kind of memory. The kinds of biological changes to the brain that occur involve both chemical and structural changes at the level of synapses – the point where a transmission of a nerve impulse from one nerve cell to another occurs.

In the case of short-term memory the brain neurons are temporarily altered. Studies have shown that brain neurons show an increase or decrease in readiness to release neurotransmitter molecules (chemical substances that transmit nerve impulses across a synapse – the space between nerve cells) into a synapse for a short amount of time when an animal is developing a short-term memory.

When developing a long-term memory lasting structural changes occur in the brain. It is believed that these changes take time to develop fully. This time period is called consolidation and can last several weeks or years in human beings. While the exact biochemical and molecular changes involved have not been defined, it is believed that through stimulation receiving brain neurons become more receptive to the next signal that comes a long and the brain structure is altered allowing for dendrite growth and an increase in the number of synapses.

Human memory is a complex phenomenon, and involves several areas of the brain. Short-term memory mostly takes place in the frontal and pre-frontal parts of the brain. The hippocampus and the cortical structures around it are mostly responsible for long-term memories. The hippocampus thus plays a fundamental role in episodic, semantic and spatial memory. Emotional memory appears to involve another structure of the limbic system besides the hippocampus. This structure is the amygdala. Procedural memory, such as knowing how to ride a bike, does not appear to involve the hippocampus at all. Instead, procedural memory appears to be associated with modifications in the cerebellum, the basal ganglia, and the motor cortex.

It is also believed that hormones can also affect the brain’s ability to store memories. Hormones released by the adrenal glands during stress and emotional arousal can enhance memory, however extreme amounts can have the opposite effect. No one knows exactly how the brain stores information, how different memory circuits link up to one another or how information is located and retrieved by the brain. There is still much to be learned about the biology of the brain.

How We Remember

Information must be encoded in order to be remembered. This is done by encoded information. An example of effortful encoding is studying. Rehearsing is also an effective technique for remembering information. There are three significant ways of rehearsing information in order create lasting memories: Maintenance rehearsal (rote memorization), elaborative rehearsal (making associations between already stored information and new information), and deep processing (the process of meaning rather than simply the physical or sensory features of a stimulus).

Reading, reciting and reviewing are examples of elaborate and deep processing and more effective tools for encoding information than just reading and rereading or studying alone. Retrieval practice such as testing also increases the ability of persons to recall information that has been memorized. In addition to elaborative rehearsal, deep processing and strategies such as reading reciting and reviewing, people who want to increase their ability to remember use formal strategies or tricks to help encode information in order to store and retain it. These are called mnemonic devises.

Why We Forget

Forgetting isn’t really a bad thing, it is actually a phenomenon. Imagine if you remembered every detail of every minute of our lives. Failing to remember something doesn’t mean the information is gone forever. Sometimes the information is there only we cannot access it. Other reasons we forger is something called repression, which is where we push a memory out of reach, because we do not want the feelings associated with the feelings.

A classic experiment, conducted to study the interference in forgetting. The experiment was conducted with only two subjects, they we both taught the same thing. After learning, one group slept while the other preformed their normal routine. The results showed the group who slept, retained more information longer. Two types of interference are proactive interference and retroactive interference (Loftus, 1980).

Decay theory is information in the memory that eventually disappears if the information is not accessed. The term decay theory was first coined by Edward Thorndike in his book “The Psychology of Learning” in 1914. This simply states that if a person does not access and use the memory representation they have formed the memory trace will fade or decay over time. One of the biggest criticisms of decay theory is that it cannot be explained as a mechanism and that is the direction that the research is headed.

Childhood Amnesia

Childhood amnesia, despite being a universal human experience, was only first formally studied in 1893 by the psychologist Caroline Miles in her article “A study of individual psychology”, published in the American Journal of Psychology. In 1904 G. Stanley Hall noted the phenomenon in his book Adolescence, but it was Sigmund Freud who offered one of the first, most famous, and most controversial descriptions and explanations of childhood amnesia when he tied the phenomenon in with psychoanalysis. Childhood amnesia is the inability to remember the events and experiences that occurred during the first three years of life. Sigmund Freud’s theories of psychosexual development are highly intertwined with childhood experiences. In what is now published as The Standard Edition of the Complete Psychological Works of Sigmund Freud, Freud theorized that childhood amnesia is the result of the mind’s attempt to repress memories of traumatic events that, according to Freud, necessarily occur in the psychosexual development of every child. This would lead to the repression of the majority of the memories of the first years of life. Freudian theory, including his explanation for childhood amnesia, has been criticized for extensive use of anecdotal evidence rather than scientific research, and said to frequently permit multiple interpretations.


Ashcraft, M., & Radvansky, G. (2010). COGNITION. Upper Saddle River: Prentice Hall.

Loftus, E.F. (1980). Memory, Reading, MA: Addison-Wesley

Wade, C., & Tavris, C. (2011). Psychology. Upper Saddlie River: Prentice Hall.

Molecular basics

Interacting with a new thing triggers a cascade of molecular events. These molecular events lead to the formation of new memories. Changes that may occur at molecular level include

  • Modification of synapses
  • Creation of new synapses
  • Modification of proteins
  • New protein synthesis
  • Activation of gene expression

According to some studies, high central nervous systems levels of acetylcholine aid in memory encoding during wakefulness. Whereas low levels of acetylcholine during sleep aid in proper consolidation of memories.

The ability of the brain to create or destroy neural synapses is termed as synaptic plasticity. Synaptic plasticity is the basis for learning. In learning experience, the reactions that are favored are reinforced and unfavorable reactions are weakened. So, the synaptic modifications can operate either way. In the short-term, synaptic changes may include modifications of pre-existing proteins leading to strengthening or weakening of a neural connection. In the long-term, entirely new synaptic connections may form.


The anatomical evidence just described suggests functional distinctions between medial temporal regions that are confirmed by substantial evidence from studies on the effects of selective damage to these areas and by characterizations of the firing properties of neurons in these areas.

Perirhinal and Lateral Entorhinal Cortex

Substantial evidence from studies on animals indicates that neurons in the perirhinal cortex and lateral entorhinal cortex are involved in the representation of and memory for individual perceptual stimuli. Electrophysiological studies on monkeys and rats performing simple recognition tasks have shown that many cells in the perirhinal cortex exhibit enhanced or suppressed responses to stimuli when they re-appear in a recognition test (Suzuki and Eichenbaum, 2000). Complementary studies in animals with damage to the perirhinal cortex indicate that this area may be critical to memory for individual stimuli in the delayed nonmatching to sample task in rats (Otto and Eichenbaum, 1992) and monkeys (Suzuki et al, 1993). These and other data have led several investigators to the view that the perirhinal cortex is specialized for identifying the strength of memories for individual stimuli (Brown and Aggleton, 2001).

Parahippocampal and Medial Entorhinal Cortex

The parahippocampal cortex and MEA may be specialized for processing spatial context. Although perirhinal and lateral entorhinal neurons have poor spatial coding properties, parahippocampal and medial entorhinal neurons show strong spatial coding (Hargreaves et al, 2005). Correspondingly, though object recognition is impaired after perirhinal damage, object-location recognition is deficient after parahippocampal cortex damage in rats (Gaffan et al, 2004) and monkeys (Alvarado and Bachevalier, 2005). Similarly, perirhinal cortex damage results in greater impairment in memory for object pairings whereas parahippocampal cortex lesions result in greater impairment in memory for the context in which an object was presented (Alvarado and Bachevalier, 2005).


Recent studies using sophisticated signal detection analysis have shown that, as in humans, in rodents recognition memory is supported by a combination of familiarity for previously experienced stimuli and recollection of specific episodes involving those stimuli, and the recollective component of recognition memory depends on the hippocampus (Fortin et al, 2004 Sauvage et al, 2008). In addition, corresponding to the commonly held view that episodic recollection involves memory for the spatial and temporal context of specific experiences, several investigators have argued that animals are indeed capable of remembering the context in which they experienced specific stimuli, and that this capacity also depends on the hippocampus (Clayton and Dickinson, 1998 Day et al, 2003). For example, Ergorul and Eichenbaum (2004) developed a task that assesses memory for events that involve the combination of an odor (‘what’), the place in which it was experienced (‘where’), and the order in which the presentations occurred (‘when’). On each of a series of events, rats sampled an odor in a unique place along the periphery of a large open field. Then, memory for when those events occurred was tested by presenting a choice between an arbitrarily selected pair of the odor cups in their original locations. Analyses of the data on these choices plus other probe tests showed that rats normally use a combination of ‘where’ and ‘what’ information to judge ‘when’ the events occurred whereas rats with hippocampal damage cannot effectively combine ‘what’, ‘when’, and ‘where’ qualities of each experience to compose the retrieved memory. Figure 3 provides an illustration of this model.

A proposed functional organization of the medial temporal lobe memory system (Eichenbaum et al, 2007). Neocortical input regarding the object features (‘what’) converges in the perirhinal cortex (PRC) and lateral entorhinal area (LEA), whereas details about the location (‘where’) of objects converge in the parahippocampal cortex (PHC) and medial entorhinal area (MEA). These streams converge in the hippocampus, which represents items in the context in which they were experienced. Reverse projections follow the same pathways back to the parahippocampal and neocortical regions. Back projections to the PHC–MEA may support recall or context, whereas back projections to the PHC–LEA may support recall of item associations.

Consistent with these findings, many studies have shown that hippocampal neurons encode many features of events and the places where they occur (Eichenbaum, 2004). For example, in one study, rats performed a task in which they had to recognize any of nine olfactory cues placed in any of nine locations (Wood et al, 1999). As the location of the discriminative stimuli was varied systematically, cellular activity related to the stimuli and behavior could be dissociated from that related to the animal's location. Some hippocampal cells encoded particular odor stimuli, others were activated when the rat sampled any odor at a particular place, and yet others fired associated with whether the odor matched or differed from the earlier cue. However, the largest subset of hippocampal neurons fired only associated with a particular combination of the odor, the place where it was sampled, and the match–nonmatch status of the odor. Another study examined the firing properties of hippocampal neurons in monkeys performing a task in which they rapidly learned new scene–location associations (Wirth et al, 2003). Just as the monkeys acquired a new response to a location in the scene, neurons in the hippocampus changed their firing patterns to become selective to particular scenes.

The combination of findings from the anatomy and functional characterizations in animal models are consistent with the anatomically guided hypothesis about the functional organization of the hippocampal system and suggest mechanisms by which the anatomical components of this system interact in support of the phenomenology of episodic recollection. After experience with a stimulus, the perirhinal and LEAs may match a memory cue to a stored template of the stimulus, reflected in suppressed activation that may signal the familiarity of previously experienced stimuli but does not provide information about where or when it was experienced. Outputs from perirhinal and LEAs back to neocortical areas may be sufficient to generate the sense of familiarity without participation of the hippocampus. In addition, during the initial experience, information about the to-be-remembered stimulus, processed by the perirhinal and LEAs, and about the spatial and possibly nonspatial context of the stimulus, is processed by the parahippocampal and MEAs, converge in the hippocampus. During subsequent retrieval, presentation of the cue may drive the recovery of object-context representations in the hippocampus that, through back projections, regenerates a representation of the contextual associations in parahippocampal and MEAs, which cascades that information back to neocortical areas that originally processed the item and contextual information. This processing pathway may constitute a principal mechanism for episodic recollection of unique events across species (Eichenbaum et al, 2007). Notably, there are also direct connections between perirhinal and parahippocampal cortex and between zones of the entorhinal cortex (Burwell et al, 1995 Suzuki and Amaral, 1994). One possibility is that these connections are strengthened over time after learning through reactivations that involve loops through the hippocampus, and these connections within cortical areas might support a gradual consolidation of memories in those cortical areas (Eichenbaum et al, 1999) this mechanism could explain why retrograde amnesia reaches farther back in time when damage to the MTL includes cortical areas in addition to the hippocampus (Rempel-Clower et al, 1996).

As described below, studies on humans have shown that a specific set of neocortical areas beyond the MTL also has important functions in episodic memory. Studies of the role in episodic memory of neocortical areas are far less developed in animals. However, recent evidence suggests that at least some cortical areas may also have a critical function in episodic memory in animals. In one such study, rats with damage to the prefrontal cortex were tested on recognition memory using signal detection analysis methods (Farovik et al, 2008). The results showed that damage to the prefrontal cortex results in a selective deficit in recollection with spared familiarity, similar to the effects of damage to the hippocampus. However, the detailed pattern of performance characterized in the signal detection analyses showed that the nature of the recollection impairment after prefrontal damage was different from that after hippocampal damage. Specifically, damage to the hippocampus resulted in forgetting of items previously seen in the study phase, whereas damage to the prefrontal cortex resulted in false-positive responses to items that were not seen in the study phase but were experienced in prior study lists. Thus, as in humans, the prefrontal cortex may have a selective function in episodic memory by monitoring and selecting retrieved memories.

Brain structures involved

Cognitive neuroscience has focused on examining what functions each brain region performs and which brain structures participate in the performance of each mental activity.

In the case of the formation of new episodic memories, the intervention of the medial temporal lobe is required. This structure includes the hippocampus , The region of the brain most involved with memory processes.

Without the intervention of the medial temporal lobe it would be possible to generate new procedural memories. For example, a person could learn to play the piano, ride a bicycle or write.

However, without intervention of the medial temporal lobe it would be impossible to remember the events experienced during the learning process. For example, a person might learn to ride a bicycle but he would not remember how he did it or what happened when he practiced.

On the other hand, the prefrontal cortex, specifically the part of the prefrontal cortex corresponding to the left cerebral hemisphere, is also involved in the generation of new episodic memories.

Specifically, the prefrontal cortex is responsible for carrying out the processes of semantic memory coding. Thus, people who have this damaged brain region are able to learn new information but often do so in the wrong way.

The most common is that subjects with the damaged prefrontal cortex are able to recognize an object they have seen in the past, but present difficulties in remembering where and when they saw it.

In this sense, several investigations have shown that the prefrontal cortex is in charge of organizing the information to facilitate a more efficient storage. In this way, it would fulfill a role within the scope of the executive function.

However, other studies suggest that the prefrontal cortex would be more involved in the development of semantic strategies that favor the codification of information, such as establishing meaningful relationships between already learned content and new information.

In summary, episodic memory appears to be played by two major brain structures: the medial temporal lobe and the prefrontal cortex. However, the operation and activity of the latter is somewhat more controversial today.

Exploring the principles of episodic memory

Susumu Tonegawa. PHOTO: RIKEN-MIT

“Since Ancient Greece, people have believed that memory is information that comes from what one experiences and then stores in the brain: that this experience, this episode, changes something physically and chemically in the brain,” explains Susumu Tonegawa. “The big question that we answered was: is this theory correct?”

Tonegawa, winner of the 1987 Nobel Prize in Physiology or Medicine, is the director of the RIKEN-MIT Laboratory for Neural Circuit Genetics at the Massachusetts Institute of Technology in Boston, USA. He is an expert on the neurological principles of learning and memory and was invited as a keynote speaker for the EMBO | EMBL Symposium ‘Probing Neural Dynamics with Behavioural Genetics’, which took place at EMBL Heidelberg in April. After finishing his lecture, he sits in an empty room one floor above the crowded foyer of the Advanced Training Centre and explains what has changed in his research field since his last visit to EMBL in 2010.

An important event for neuroscience in the last decade was finding proof of the engram theory, Tonegawa explains. This theory was formulated in 1904 by the German memory researcher Richard Semon in his book The Mneme. Semon used the word ‘engram’ to describe physical and chemical changes in the brain network that encode memories. In order for the engram theory to be correct, three principles must be fulfilled: brain cells must be activated by an experience, undergo lasting changes caused by this experience, and it must be possible to retrieve the memory of the experience. An encounter with a similar stimulus, like a smell, can reactivate the changed neurons and trigger the memory.

“Our lab found a population of cells in the hippocampus which satisfied these three conditions for specific memory: activation by experience, enduring changes in those cells and then reactivation of those cells,” says Tonegawa.

By artificially stimulating certain brain areas in a mouse, it was possible to trigger the memory of a negative experience the animal had undergone and cause a fear reaction. “Our key discovery here is that it is possible to artificially mimic a mental process,” Tonegawa explains. “The three conditions set out in the engram theory of memory are satisfied by our set of experiments: Semon’s engram theory is correct.”

This artificial triggering of memories also opens the door to medical applications, for example the stimulation of positive memories to fight depression. This, however, has only been tested in mice, as the process is still too invasive to be carried out in humans.

Studying memory engrams also shows that assumptions about Alzheimer’s disease need to be re-evaluated. It was believed that Alzheimer’s inhibits the brain’s ability to form memories. Research in mouse model organisms shows that memories can still be formed, but not retrieved. Artificial stimulation of marked engrams in the hippocampus triggered fear responses in mice with early Alzheimer’s disease, showing that a fear-based memory had been formed and could be accessed artificially.

“It’s possible that in the future there will be a new type of therapy that doesn’t depend on drugs,” says Tonegawa. “Chemical therapy works, but there are all these side-effects, and also patients vary in their susceptibility to certain medications. I’m sure that physical therapy would also have side-effects, but a different kind. Therefore it might be possible to combine chemical therapy with physical therapy, in a way that means more people can be treated.” As Tonegawa explains, this form of therapy would require further technological advancements in brain cell manipulation, based on fundamental memory research.

“It’s important that we show the public how important fundamental research is,” says Tonegawa. “We have to find out what’s going on in the brain, independently of potential applications. If you need to find a therapy for an abnormal brain, first you need to know how a normal brain works. That’s fundamental research, like most of the work done at EMBL. The value of fundamental research can never be emphasised enough. You can’t just come up with a new therapy by magic.”

Concluding remarks

Two decades of functional imaging have greatly enhanced our understanding of the cognitive neuroscience of ageing 86 . For episodic memory, the imaging findings confirm a key role of the hippocampus 87 , but also suggest that the importance of the hippocampus can only be understood in the context of a large-scale brain network (Table 1). This knowledge can guide attempts to strengthen memory in older adults by various forms of intervention. Past studies indicate a high degree of process and regional specificity of specific forms of intervention 88, 89 , suggesting that it is vital to tailor interventions in ageing to specifically influence the hippocampus/MTL. This can be achieved by means of cognitive interventions 90-92 and also through physical (exercise) interventions 93-95 . It is likely that a combination of cognitive and physical stimulation has the greatest potential to support memory and cognition 96 . Additional promising routes to support hippocampus-based memory functioning include stress 97 , dietary 98 and sleep 99 interventions. It is possible that interventions targeting regions in the extended episodic memory network, such as the prefrontal cortex or the dopamine system 100 , could also be effective and translate into strengthening of hippocampus-based episodic memory functioning.

Watch the video: Πώς μπορούμε να αναπτύξουμε νέους νευρώνες στον εγκέφαλο. TED (May 2022).