- Memory refers to the neurological processes that are used to encode, store, retain, and retrieve information from the perceived world and our own introspection.
- The hippocampus has been recognized as playing a vital role in formation of declarative memory in particular, which describes the synthesis of episodic memory (i.e. your personal memory) and semantic (or factual) memories.
- Different types of memory require the involvement of different brain regions/structures. (Table 1)
- The hypothesis that if two neurons are active at the same time, the synaptic efficiency of the appropriate synapse will be strengthened, lead to the development of the Long Term Potentiation model.
- According to the notion that learning and memory are mediated by changes in the strength of synapses in neural circuits, neural activity during learning gives rise to long-term changes in synaptic strength, which is both necessary and sufficient for memories to be stored and later retrieved.
- If one or more axons connected to a dendrite bombard it with a rapid series of stimulation, which leaves the synapses more responsive to new input of the same type for minutes, days, or weeks.
- LTP has several characteristics – LTP is input-specific; simultaneous stimulation by multiple axons produces LTP considerably larger than does repeated stimulation by only one axon; LTP is an associative process.
- The biochemical mechanism of LTP involves AMPA and NMDA receptors, which are types of glutamatergic ion channels that exist on dendritic membranes, where the binding of glutamate occurs (glutamate is an excitatory neurotransmitter).
- If reading is not your thing and you want to learn more about LTP, watch the video at the bottom of the article (2 minutes).
What is Memory?
Memory can be considered as an organically-based activity in which information from the perception of the external world or introspection results in an alteration of neural pathways (i.e., encoding; Klein, 2015). These pathways are established and are usually subject to considerable and ongoing modification in various cortical regions (i.e., storage; Klein, 2015). These pathways must be causally linked to changes in an organism’s behaviour (mental and/or physical) at some point in time following their acquisition (i.e., retrieval; Klein, 2015). This definition is sufficiently general to encompass most contemporary views of memory. However, there are issues and controversies that it does not directly address. Is memory conscious or unconscious? Is memory a process or a substance? Is it malleable or stable? Despite these issues and controversies, most neuroscientists subscribe, with minor reservations, to the above definition. Simply, memory refers to the neurological processes that are used to encode, store, retain, and retrieve information from the perceived world and our own introspection.
Though the above definition of memory is adequate, there is yet another problem with it. There are approximately 68 billion neurons inside the human brain. Does memory occur in every neuron? Or just a select few? Where exactly does memory occur? These are questions that have been a major focus of contemporary work in the field of neuroscience.
The Physical Representation of Memory
The collection of neuronal changes representing memory is commonly known as the engram – a physical representation of something that has been learnt (Thompson, 1976). Most modern neuroscientists argue that the engram is the changes at the synapses between neurons, and that memory depends on these changes in the hippocampus. There are several areas of the brain that play a part in consolidation of several forms of memory (see Table 1), but the hippocampus has been recognized as playing a vital role in formation of declarative memory in particular, which describes the synthesis of episodic memory (i.e. your personal memory) and semantic (or factual) memories (Lynch, 2004). We are able to make these determinations when we compare healthy human brains to pathological human brains.
In 1953, Henry Molaison (also known as H. M.) was suffering from chronic seizures which was unaffected by every available antiepileptic drug. As a last-resort treatment option for H.M., a surgeon removed his hippocampus and nearby structures of the medial temporal cortex from both hemispheres (Scoville & Milner, 1957). The surgery was effective in removing the patient’s epilepsy, but it also resulted in anterograde amnesia (difficulties in forming new memories). This explicitly identified the importance of the role of the hippocampus and temporal lobe structures in memory (Lynch, 2004). Recently, non-invasive methods using direct brain imaging techniques such as magnetic resonance imaging (MRI) and positron emission tomography (PET) characterised blood flow and oxygen use in the hippocampus and identified fluctuations in these parameters during learning tasks (Lynch, 2004), which indicates that the hippocampus is active while learning new information.
Table 1. Types of Memory and Their Associated Brain Region
|Type of Learning/Memory||Brain Areas|
|Habituation – the process of growing accustomed to a situation or stimulus||Basal ganglia|
|Spatial learning – the process by which we acquire a mental representation of our environment||Hippocampus|
Posterior parietal cortex
|Emotional memory – the memory of experiences that evoked an emotional reaction||Amygdala|
|Recognition memory – the ability to identify a familiar stimulus or a situation that you have encountered previously||Hippocampus|
|Working memory – keeps track of what you are doing in the moment||Hippocampus |
|Motor skills – skills that enable the movements and tasks we do every day. Fine motor skills are those that require a high degree of control and precision in the small muscles of the hand (such as using a fork). Gross motor skills use the large muscles in the body to allow for balance, coordination, reaction time, and physical strength so that we can do bigger movements, such as walking and jumping.||Striatum|
|Sensory memory (visual, auditory) – a very brief memory that allows you to retain an impression of and for your brain to start processing what you see, feel, touch etc.||Various cortical structures|
|Classical conditioning – a type of learning process that happens unconsciously.||Cerebellum|
Cajal (1911) originally hypothesized that information storage relies on changes in strength of synaptic connections between active neurons. A synapse is a small pocket of space between two neurons, where information/messages are passed on from one neuron to the next in order relay communicate. Hebb (1949) supported this hypothesis and proposed that if two neurons are active at the same time, the synaptic efficiency of the appropriate synapse will be strengthened. This research sparked enormous effort being channelled into understanding the mechanism by which strengthening of synaptic connections can be achieved, which led to the development of a model called long-term potentiation (LTP; Bliss & Lomo, 1973). This tremendous amount of attention was fuelled to a large degree by the widely held hypothesis that learning and memory are mediated by changes in the strength of synapses in neural circuits (Sigurdsson et al., 2007). According to this hypothesis, neural activity during learning gives rise to long-term changes in synaptic strength, which is both necessary and sufficient for memories to be stored and later retrieved (Lynch, 2004). Simply, if one or more axons connected to a dendrite bombard it with a rapid series of stimulation, which leaves the synapses more responsive to new input of the same type for minutes, days, or weeks.
LTP is a persistent increase in synaptic strength and shows three properties that have made it an attractive candidate for a cellular basis of learning and memory (Kalat, 2015):
LTP is input-specific, which is likely to increase the storage capacity of neural circuits that are capable of LTP (Sigurdsson et al., 2007). If some of the synapses between neurons have been highly active and others have not, only the active synapses become strengthened.
Nearly simultaneous stimulation by multiple axons produces LTP considerably larger than does repeated stimulation by only one axon.
LTP is associative in that its induction typically requires coincident pre-and postsynaptic activity, making it suitable for encoding associations in the external world (Sigurdsson et al., 2007). Pairing a weak input with a strong input results in an enhancement of later responses to the weak input. In some cases, an almost completely inactive synapse before LTP becomes effective afterwards.
The opposite change, long-term depression (LTD), an extensive decrease in response at a synapse, occurs for axons with a history of minimal activity. This is a compensatory process – as one synapse strengthens, another weakens (Kalat, 2015). If learning produced only strengthening of synapses, the brain would require extraordinary amounts of energy due to consistent brain activity of all regions. Taken together, these properties lend face validity to the hypothesis that LTP and LTD-like changes underlie learning and memory (Sigurdsson et al., 2007).
Biochemical Mechanisms of LTP and LTD
Thus far, we know that LTP is a term that is used to describe the strengthening of the synapse between neurons, resulting in a greater likelihood of post-synaptic firing. But how exactly do the synapses become strengthened? Determining how LTP and LTD occur has been challenging because each neuron has thousands of synapses. Isolating the chemical changes at any one synapse is difficult, and it takes large amounts of creative and patient research. However, in recent history, physiological and biochemical changes at the synapse have since been described. Initial studies in rats, which were later confirmed in humans, suggested that the induction of LTP requires activation of both α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors in the postsynaptic neuron (Bear & Malenka, 1994; Sweatt, 1999), which leads to postsynaptic calcium entry and activation of calcium-dependent kinases.
AMPA and NMDA receptors are types of glutamatergic ion channels that exist on dendritic membranes, where the binding of glutamate (glutamate is an excitatory neurotransmitter) occurs that allows for the influx of sodium and calcium, depolarising the neuron, leading to an action potential. The figures below describe the exact process of how the pre-synaptic and post-synaptic neuron interact to undergo LTP.
The axon releases glutamate, which binds to AMPA and NMDA receptors. While glutamate is bound to the AMPA receptor, sodium enters the post-synaptic neuron through the open channel. At the NMDA receptor, glutamate binds but fails to open the channel, which is blocked by magnesium ions.
Intense Neuronal Firing and Entry of Calcium
If one or more AMPA receptors have been repeatedly stimulated, enough sodium enters the post-synaptic neuron to depolarise it. This depolarisation displaces the magnesium ion at the NMDA receptor, through which sodium and calcium enter. This greatly depolarises the post-synaptic neuron.
LTP at the Post-Synaptic Neuron
The entry of calcium into the post-synaptic neuron activates a protein called CaMKII, which further releases a protein called CREB. CREB enters the nucleus of the neuron and alters the expression of several genes. These altered gene expressions usually result in an increase in AMPA and NMDA receptors at the post-synaptic neuron, strengthening the future responsiveness to glutamate. LTP can also result in an increase in more dendritic branches and spines – forming additional synapses with the same axon, as well as creating phosphate groups that bind to AMPA receptors, making them more responsive (Kalat, 2015). LTP at the post-synaptic neuron reflects an increase in responsiveness. LTP can last up to years – long enough to account for long-term memory (Miller et al., 2010).
LTP at the Pre-Synaptic Neuron
LTP can also occur at the pre-synaptic neuron. A retrograde transmitter (usually nitric oxide) from the post-synaptic neuron will travel back to the pre-synaptic neuron under extensive stimulation. Consequently, the pre-synaptic neuron will decrease its threshold for producing action potentials, increase the release of glutamate, and release glutamate from more sites on the axon terminal (Kalat, 2015). LTP at the pre-synaptic neuron reflects increased activity.
If reading is not your thing and you want to learn more about LTP, watch this video below!
Latest From Instagram
Bear, M. F., & Malenka, R. C. (1994). Synaptic plasticity: LTP and LTD. Current opinion in neurobiology, 4(3), 389-399.
Bliss, T. V., & Lømo, T. (1973). Long‐lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. The Journal of physiology, 232(2), 331-356.
y Cajal, S. R. (1911). Histologie du système nerveux de l’homme & des vertébrés: Cervelet, cerveau moyen, rétine, couche optique, corps strié, écorce cérébrale générale & régionale, grand sympathique (Vol. 2). A. Maloine.
Hebb, D. O. (1949). The first stage of perception: growth of the assembly. The Organization of Behavior, 4, 60-78.
Kalat, J. W. (2015). Biological psychology. Cengage Learning.
Klein, S. B. (2015). What memory is. Wiley Interdisciplinary Reviews: Cognitive Science, 6(1), 1-38.
Lynch, M. A. (2004). Long-term potentiation and memory. Physiological reviews, 84(1), 87-136.
Miller, C. A., Gavin, C. F., White, J. A., Parrish, R. R., Honasoge, A., Yancey, C. R., … & Sweatt, J. D. (2010). Cortical DNA methylation maintains remote memory. Nature neuroscience, 13(6), 664-666.
Sigurdsson, T., Doyère, V., Cain, C. K., & LeDoux, J. E. (2007). Long-term potentiation in the amygdala: a cellular mechanism of fear learning and memory. Neuropharmacology, 52(1), 215-227.
Squire, L. R. (1986). Mechanisms of memory. Science, 232(4758), 1612-1619.
Sweatt, J. D. (1999). Toward a molecular explanation for long-term potentiation. Learning & Memory, 6(5), 399-416.
Thompson, R. F. (1976). The search for the engram. American Psychologist, 31(3), 209.
Featured Image Credit adike/Shutterstock
More from the NeuroBlog
How can Neurofilament light concentrations help in Diagnosis?
Overview In May 2022, I attended a conference in Syndey, Australia. The conference was targeted mainly for psychiatrists and neuropsychiatrists. I was able to attend this lovely conference through my company called Monarch Mental Health Group. On the first day, the conference kicked off by an invited keynote speaker. This speaker was a psychiatrist, and…
Execessive Neural Noise in Developmental Dyslexia?
Overview Developmental dyslexia (reading disabilities/disorders, or decoding-based reading disorder) is a neurodevelopmental disorder with multiple potential underlying genetic, neural, and cognitive factors.Past models have not been very successful at integrating key neural and behavioural features of dyslexia with common neural processes, until Hancock et al. (2017) proposed their dyslexia model. Dyslexia risk genes indicate two…
Debunking Popular Neuromyths: Do You Use Your Entire Brain?
It is the summer of 2014 on Earth’s Northern hemisphere and the movie Lucy is hitting theatres. The official promotional posters and movie trailers contain the tagline “The average person uses 10% of their brain capacity. Imagine what she could do with 100%.” Lucy becomes the second most successful debut for a French action film,…
1 thought on “How Do You Store Memories?”