The Brain Chemistry of Memory

The Brain Chemistry of Memory

 
 
 

Summary

 

The brain chemistry of memory refers to the complex biochemical processes and neurotransmitters that underpin the encoding, storage, and retrieval of memories in the human brain. Memory is fundamentally categorized into short-term and long-term types, with distinct neurobiological mechanisms driving each. Short-term memory, or working memory, enables individuals to temporarily hold and manipulate information, while long-term memory encompasses the more durable storage of knowledge and experiences. Understanding these processes is crucial as they provide insights into cognitive functions and the implications of memory-related disorders. At the core of memory formation are neurotransmitters such as glutamate, acetylcholine, dopamine, and serotonin, which facilitate communication between neurons. Glutamate plays a key role in synaptic plasticity, a process essential for learning and memory consolidation, while acetylcholine is critical for attention and memory retrieval. Research has established that disruptions in neurotransmitter levels can significantly impair memory functions, highlighting the intricate relationship between brain chemistry and cognitive health, particularly in conditions like Alzheimer's disease and other neurodegenerative disorders. Moreover, the emotional context of memory formation is vital; the arousal theory posits that stronger emotional experiences lead to enhanced memory retention. The interplay between neurotransmitters and emotional arousal is evidenced by phenomena such as flashbulb memories, where intense emotional experiences result in vivid recollections. This suggests that not only is the biochemical composition of memory important, but the emotional context also plays a significant role in how memories are encoded and recalled. Controversies surrounding the brain chemistry of memory primarily revolve around the extent to which neurotransmitters influence different memory types and the varying impacts of stress on memory retrieval and consolidation. While acute stress can enhance memory formation, it may hinder the ability to recall those memories later. This nuanced relationship between neurotransmitter activity, emotional states, and cognitive processes underscores the complexity of memory and the need for continued research in this dynamic field.
 
 

Overview of Memory Types

 

Memory can be broadly categorized into different types based on the processes of encoding, storage, and retrieval. The two primary categories of memory are short-term memory and long-term memory.
 

Short-Term Memory

 

Short-term memory, often referred to as "working memory," is a temporary storage system that holds a limited amount of information for a brief period. Researchers have identified that the capacity and duration of short-term memory can be manipulated using various strategies[1][2]. This memory system allows individuals to organize, process, and utilize information, which is essential for cognitive tasks[3].
 

Long-Term Memory

 
Long-term memory encompasses information that is stored more permanently.
 

Explicit Memory

 

Explicit memory, also known as declarative memory, involves memories that can be consciously recalled and articulated. This type of memory is primarily encoded by structures in the brain such as the hippocampus and the entorhinal cortex[4][5]. Explicit memory is crucial for recalling facts and events, and its retrieval often relies on the coordinated efforts of various brain regions, including those within the limbic system[4].
 
 

Implicit Memory

 
In contrast to explicit memory, implicit memory refers to memories that are acquired and recalled unconsciously. Research suggests that the cerebellum, basal ganglia, motor cortex, and various areas of the cerebral cortex play significant roles in the storage and retrieval of implicit memories[6]. Implicit memory is often associated with procedural learning and skills, demonstrating that not all memory processes require conscious awareness.
 
 
 
 

Memory Processes

 

The formation of memories involves a complex interplay of brain structures and biochemical processes. Memory formation begins in the hippocampus, which is located in the temporal lobes of the brain[1][2]. This region is critical for the retrieval of memories, aided by the coordinated activity of neurons, neurotransmitters, and synapses throughout various brain regions[1][3]. Each memory encompasses four essential components: gathering, encoding, storing, and retrieving information, highlighting the intricacy of memory processing in the human brain[2][3].
 
 
 
 

Neurotransmitters Involved In Memory

 
 

The process of memory formation is intricately linked to various neurotransmitters that play critical roles in encoding, consolidation, and retrieval of memories. Key neurotransmitters implicated in memory include epinephrine, dopamine, serotonin, glutamate, and acetylcholine[7][8][9].
 
 

Emotional Impact on Memory

 
The relationship between emotion and memory is underscored by the arousal theory, which posits that stronger emotional experiences lead to stronger memory formation. This is because strong emotions trigger the release of neurotransmitters and hormones that enhance memory consolidation[10][11]. The phenomenon of flashbulb memories, where vivid recollections of significant events occur, exemplifies this connection between emotional arousal and enhanced memory retention[10].
 
 
 

Brain Regions Associated with Memory

 
 
 
Memory is a complex cognitive function that involves several key brain regions, each playing distinct roles in the encoding, storage, and retrieval of information. The primary areas associated with memory include the hippocampus, amygdala, cerebellum, and prefrontal cortex.
 
 
 

The Hippocampus

 
The hippocampus is a crucial structure for memory formation, particularly in the context of long-term memory. It is part of the hippocampal formation, which also includes the dentate gyrus and the subiculum. These components are situated in the interior of the temporal lobe and are organized in a manner reminiscent of the letter C. Together, they represent the main areas of the brain implicated in the development of long-term memories[12][13][4]. The hippocampus is extensively studied for its role in retrieval mechanisms as well as the acquisition of memories[14].
 
 

The Amygdala

 
 
The amygdala is another significant brain region involved in memory, particularly in enhancing the encoding of memories associated with emotional experiences. It appears to facilitate deeper encoding of events that are emotionally arousing, thereby influencing the strength and vividness of memories[15][16]. This emotional aspect of memory encoding underscores the amygdala's importance in both memory formation and retrieval, especially for autobiographical memories[17].
 
 
 
 

The Prefrontal Cortex

 

The prefrontal cortex is essential for working memory and plays a critical role in maintaining task-relevant information temporarily. It is often associated with rehearsal processes during memory tasks, where its activity is heightened during delay periods[18][19]. Recent research suggests that the prefrontal cortex may not simply act as a storage area for long-term memory encoding; rather, it might provide top-down signals that help modulate encoding in posterior sensory and association areas, where actual working memory representations are held[18][19][20]. This nuanced understanding of the prefrontal cortex's function highlights its pivotal role in the integration and management of cognitive processes related to memory.
 

The Cerebellum

 
While the cerebellum is primarily known for its involvement in motor control, it also plays a role in certain types of memory, particularly procedural memory. This type of memory relates to the skills and tasks that require practice and refinement, such as riding a bicycle or playing a musical instrument. The cerebellum helps coordinate these actions and contributes to the automaticity of learned behaviors, thereby influencing memory retention and recall in a more indirect manner[21][22].
 
 
 

Mechanisms of Memory Formation

 
 
Memory formation is a complex process that involves various neurobiological mechanisms, primarily centered around synaptic plasticity and the role of neurotransmitters.
 

Synaptic Plasticity

 
 
Synaptic plasticity is fundamental to memory formation and refers to the ability of synapses—the connections between neurons—to strengthen or weaken over time, in response to increases or decreases in their activity. This process is a key component of neuroplasticity, which encompasses broader changes in neural circuitry. Research has shown that the modifications of synaptic transmission result in stronger or weaker connections between individual synapses, ultimately contributing to the overall function of memory[23][24][25]. Mechanisms that enable synaptic modification include synaptic vesicle release and recycling, neurotransmitter receptor trafficking, and cell adhesion. Each of these plays a crucial role in the adjustments made at synapses during learning and memory processes[23][26].
 
 
 
 

Role of Neurotransmitters

 

Neurotransmitters are critical for encoding, consolidating, and retrieving memories. They influence various aspects of memory processing and can dictate how well memories are formed and recalled. For instance, glutamate is particularly important in the formation of long-term memories, as it is involved in long-term potentiation (LTP)—a process that strengthens synaptic connections when they are repeatedly activated[27]. The equipotentiality hypothesis suggests that different brain regions can compensate for damaged areas, supporting the brain's adaptability in memory function[28][29].
 

Memory Types

 
Memory can be categorized into different types, including sensory, short-term, and long-term memory. Sensory memory briefly retains sensory information, while short-term memory has a limited capacity and duration, functioning like a temporary storage area for information[30]. Understanding the mechanisms behind these types of memory can provide insights into how we learn and retain information, as well as how various conditions may affect memory function.
 
 

Molecular and Cellular Changes in Memory

 

Memory formation involves complex molecular and cellular changes in the brain, influenced by various neurotransmitters. These changes affect the encoding, consolidation, and retrieval of memories through specific biochemical pathways[28][9].
 

Neurotransmitter Influence

 
Different neurotransmitters play critical roles in memory processes. For instance, decreased levels of serotonin (5-HT) have been shown to impair memory consolidation that depends on protein synthesis, indicating that certain neurotransmitters are essential for specific memory tasks[31]. Moreover, research indicates that while short-term and long-term memories require the activation of second messenger kinases, working memory necessitates the activity of phosphatases. This suggests that there is a molecular switch that prevents information from working memory from being stored as long-term memory[32][8].
 

Autobiographical Memory and Its Mechanisms

 
Autobiographical memory, a subset of explicit memory, consists of both episodic and semantic elements related to oneself. This memory system is intricately connected to conscious experience and self-perception. Theoretical models propose that autobiographical memories are transient constructs stored within a self-memory system that includes an autobiographical knowledge base aligned with the current goals of the individual[33][25].
 

Stress and Memory

 
Interestingly, stress can have dual effects on memory. While acute stress at the time of learning may enhance the formation of robust memories, it can severely impair the retrieval of those memories later on[34]. This highlights the nuanced relationship between stress and memory, suggesting that the same biochemical processes can yield different outcomes depending on the context of memory formation and recall.
 
 

Impact of Neurotransmitter Imbalances on Memory

 

Neurotransmitters play a critical role in the processes of memory encoding, consolidation, and retrieval. These chemical messengers facilitate communication between neurons, allowing the brain to function effectively in storing and recalling information[28][11]. An imbalance in neurotransmitter levels can significantly impair memory function, leading to various cognitive deficits[28][35].
 

Key Neurotransmitters Involved in Memory

 

Acetylcholine

 

Acetylcholine (ACh) is particularly important for memory and learning. It is involved in muscle contractions as well as cognitive processes[25]. In conditions such as Alzheimer's disease, the loss of cholinergic neurons results in decreased levels of ACh, which is strongly correlated with the cognitive decline observed in affected individuals[36][37]. Drugs that aim to increase ACh levels can help mitigate some symptoms of memory impairment associated with this disease[36].
 

Glutamate

 
Glutamate is another neurotransmitter critical for memory formation and retrieval. It facilitates synaptic plasticity, a mechanism essential for learning and memory[7][20]. Abnormal glutamate signaling has been implicated in neurodegenerative diseases, affecting cognitive function[28][20].
 

Dopamine and Noradrenaline

 
The dopamine and noradrenaline neurotransmitter systems also contribute to age-related memory impairment, influencing both the motivation to remember and the ability to focus on tasks[38]. Dysregulation of these neurotransmitters can lead to difficulties in encoding new memories and retrieving existing ones[38].
 

Other Neurotransmitters

 
Serotonin and GABA (gamma-aminobutyric acid) also play roles in memory processes, albeit in more complex ways. Research suggests that serotonin loss may directly contribute to cognitive decline rather than being a mere symptom of neurodegenerative diseases like Alzheimer's[37]. GABA, being an inhibitory neurotransmitter, helps regulate excitatory signals in the brain, which is crucial for maintaining balance in cognitive processes[39].
 
 
 
 

Consequences of Neurotransmitter Imbalance

 

When neurotransmitter levels are imbalanced, as seen in various neurodegenerative disorders, the resulting cognitive dysfunction can lead to memory deficits and other related symptoms[3][35]. In Alzheimer's disease, for example, the depletion of acetylcholine severely impacts the ability to encode new memories, demonstrating how critical these chemical messengers are to cognitive health[40][25]. Furthermore, neuroinflammation associated with neurotransmitter imbalances exacerbates cognitive decline, highlighting the intricate relationship between brain chemistry and memory[41]
. Understanding the roles of neurotransmitters in memory is vital for developing therapeutic strategies aimed at treating memory impairments and associated neurodegenerative diseases.
 
 

References

 
Reference [1]
Title: Inside the Science of Memory | Johns Hopkins Medicine
Url: https://www.hopkinsmedicine.org/health/wellness-and-prevention/inside-the-science-of-memory
Highlights: You can, however, manipulate your short-term memory by increasing the capacity and duration. There are two strategies to do this: Because you can organize, process and use information from short-term memory, researchers coined the terms “working memory” or “short-term working memory” and use them interchangeably. There are two main types of long-term memory: There are four parts to every memory: Your brain has a very specific strategy for gathering, encoding, storing and retrieving memories. It involves the coordinated efforts of neurons (nerve cells), neurotransmitters, synapses and many different brain regions. Memories form in your hippocampus. This is a part of a larger structure (temporal lobes). The temporal lobe sits behind your temples. You have a temporal lobe (and hippocampus) on each side of your head. They help with memory retrieval. Other parts of your brain participate in memory processes:
 
 
Reference [2]
Title: Alzheimer's Disease: Symptoms & Treatment - Cleveland Clinic
Url: https://my.clevelandclinic.org/health/diseases/9164-alzheimers-disease
Highlights: You can, however, manipulate your short-term memory by increasing the capacity and duration. There are two strategies to do this: Because you can organize, process and use information from short-term memory, researchers coined the terms “working memory” or “short-term working memory” and use them interchangeably. There are two main types of long-term memory: There are four parts to every memory: Your brain has a very specific strategy for gathering, encoding, storing and retrieving memories. It involves the coordinated efforts of neurons (nerve cells), neurotransmitters, synapses and many different brain regions. Memories form in your hippocampus. This is a part of a larger structure (temporal lobes). The temporal lobe sits behind your temples. You have a temporal lobe (and hippocampus) on each side of your head. They help with memory retrieval. Other parts of your brain participate in memory processes:
 
 
Reference [3]
Title: Neurotransmitter receptors and cognitive dysfunction in Alzheimer's ...
Url: https://pmc.ncbi.nlm.nih.gov/articles/PMC3371373/
Highlights: You can, however, manipulate your short-term memory by increasing the capacity and duration. There are two strategies to do this: Because you can organize, process and use information from short-term memory, researchers coined the terms “working memory” or “short-term working memory” and use them interchangeably. There are two main types of long-term memory: There are four parts to every memory: Your brain has a very specific strategy for gathering, encoding, storing and retrieving memories. It involves the coordinated efforts of neurons (nerve cells), neurotransmitters, synapses and many different brain regions. Memories form in your hippocampus. This is a part of a larger structure (temporal lobes). The temporal lobe sits behind your temples. You have a temporal lobe (and hippocampus) on each side of your head. They help with memory retrieval. Other parts of your brain participate in memory processes:Cognitive dysfunction is one of the most typical characteristics in various neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease ...
 
 
 
Reference [4]
Title: Neurotransmitter Roles in Synaptic Modulation, Plasticity and ...
Url: https://pmc.ncbi.nlm.nih.gov/articles/PMC2849868/
Highlights: Long term memory represents the final stage in the information-processing model where informative knowledge is stored permanently (the idea of memory permanences will be discussed in a later section). Memories we have conscious storage and access to are known as explicit memory (also known as declarative memory) and are encoded by the hippocampus, the entorhinal cortex, and the perihinal cortex which are important structures in the limbic system. The limbic system represents a set of brain structures located on both sides of the thalamus, immediately beneath the cerebral cortex, and is important for a variety of functions including emotion, motivation, long-term memory, and olfaction.THE HIPPOCAMPUS The hippocampal formation is made up of a group of substructures including the hippocampus, the dentate gyrus, and the subiculum all of which are located in the interior of the temporal lobe organized in a similar shape to a letter C. Together these structures represent the main areas of the brain associated with the formation of long term memories.
 
 
 
Reference [5]
Title: Ch. 7: Synaptic Plasticity | McGovern Medical School
Url: https://med.uth.edu/nba/nso/table-of-contents-2/cellular-and-molecular-neurobiology/ch-7-synaptic-plasticity/
Highlights: Long term memory represents the final stage in the information-processing model where informative knowledge is stored permanently (the idea of memory permanences will be discussed in a later section). Memories we have conscious storage and access to are known as explicit memory (also known as declarative memory) and are encoded by the hippocampus, the entorhinal cortex, and the perihinal cortex which are important structures in the limbic system. The limbic system represents a set of brain structures located on both sides of the thalamus, immediately beneath the cerebral cortex, and is important for a variety of functions including emotion, motivation, long-term memory, and olfaction.
 
 
 
Reference [6]
Title: An Expanded Narrative Review of Neurotransmitters on Alzheimer's ...
Url: https://link.springer.com/article/10.1007/s12035-024-04333-y
Highlights: In contrast to the memory systems covered above related to explicit encoding and retrieval memory processes, implicit memory as discussed in the previous section refers to memories that are acquired and recalled unconsciously. Modern research has suggested that the cerebellum, the basal ganglia (a group of subcortical structures associated with voluntary motor control, procedural learning, and emotion as well as many other behaviors), the motor cortex, and various areas of the cerebral cortex (Dharani, 2014) are related to the storage and retrieval of implicit memory. THE AMYGDALAYou can, however, manipulate your short-term memory by increasing the capacity and duration. There are two strategies to do this: Because you can organize, process and use information from short-term memory, researchers coined the terms “working memory” or “short-term working memory” and use them interchangeably. There are two main types of long-term memory: There are four parts to every memory: Your brain has a very specific strategy for gathering, encoding, storing and retrieving memories. It involves the coordinated efforts of neurons (nerve cells), neurotransmitters, synapses and many different brain regions. Memories form in your hippocampus. This is a part of a larger structure (temporal lobes). The temporal lobe sits behind your temples. You have a temporal lobe (and hippocampus) on each side of your head. They help with memory retrieval. Other parts of your brain participate in memory processes:
 
 
Reference [7]
Title: Parts of the Brain Involved with Memory - OpenEd CUNY
Url: https://opened.cuny.edu/courseware/lesson/52/student/?section=5
Highlights: . Greater activation of the amygdala predicting higher probabilities of accurate recall provides evidence illustrating how association with an emotional response can create a deeper level of processing during encoding, resulting in a stronger memory trace for later recall.There also appear to be specific neurotransmitters involved with the process of memory, such as epinephrine, dopamine, serotonin, glutamate, and acetylcholine.
 
 
Reference [8]
Title: Parts of the Brain Involved with Memory – Psychology
Url: https://pressbooks-dev.oer.hawaii.edu/psychology/chapter/parts-of-the-brain-involved-with-memory/
Highlights: There also appear to be specific neurotransmitters involved with the process of memory, such as epinephrine, dopamine, serotonin, glutamate, and acetylcholine ( ...Figure 1. Research in our laboratory has determined that the molecular mechanisms that underlie working memory are antagonistic for short- and long-term memory. We have discovered that while short- and long-term memory requires activation of second messenger kinases, working memory requires phosphatase activity. This molecular switch may represent the means by which information held in working memory is not stored more long-term. Further, this research indicates that drugs which activate protein kinases to improve short- or long-term memory may have detrimental effects on working memory.
 
 
Reference [9]
Title: Role of Neurotransmitters in Memory - JoVE
Url: https://www.jove.com/science-education/v/18188/role-of-neurotransmitters-in-memory
Highlights: The role of neurotransmitters in memory is multifaceted, influencing the encoding, consolidation, and retrieval of memories through their action ...
 
 
 
Reference [10]
Title: Neurochemistry and Molecular Neurobiology of Memory | SpringerLink
Url: https://link.springer.com/10.1007/978-0-387-30405-2_19
Highlights: Glutamate is the most prominent neurotransmitter in the brain and has been intimately linked to LTP and LTD. Approximately half of the synapses (and nearly all ...
 
 
 
Reference [11]
Title: Neurotransmitters and Memory: Cholinergic, Glutamatergic ...
Url: https://www.sciencedirect.com/science/article/abs/pii/B978012408139000002X
Highlights: Synaptic plasticity is essentially the process of neuroplasticity occurring at the single-cell level. It is the modification of neural circuitry through the malleability of the individual synapse. There is a large body of research that has elucidated the intricate workings of the synapse, uncovering how it makes modifications to the strength or efficacy of synaptic transmission as a response to stimuli, which may present itself in a myriad of forms). These modifications of synaptic transmission result in stronger or weaker connections between individual synapses, which collectively add up to the effect of neuroplasticity. Research has been able to provide insights into the underlying molecular mechanisms that allow synaptic modification to occur. Key mechanisms such as synaptic vesicle release and recycling, neurotransmitter receptor trafficking, and cell adhesion have all been implicated in synaptic plasticity, and an overview of their roles is given below.The final main group of memory under the category of explicit memory is known as Autobiographical memory. This memory system is made up of both episodic, and semantic aspects of memory and is a collection of memories specifically related to the self. This could be how you look, your height, specific meaningful points in your life, or the general idea of your concept of self. The specific locations where this type of memory are stored and accessed are especially controversial due to the close relationship between autobiographical information and conscious experience. Conway and Pleydell-Pearce (2000) suggested a model describing autobiographical memories as transitory mental compositions stored within a self-memory system containing an autobiographical knowledge base and current goals of the working self
 
 
Reference [12]
Title: Parts of the Brain Involved with Memory | Introduction to Psychology
Url: https://courses.lumenlearning.com/suny-hvcc-psychology-1/chapter/parts-of-the-brain-involved-with-memory/
Highlights: There also appear to be specific neurotransmitters involved with the process of memory, such as epinephrine, dopamine, serotonin, glutamate, and acetylcholine ( ...It is also believed that strong emotions trigger the formation of strong memories, and weaker emotional experiences form weaker memories; this is called arousal theory (Christianson, 1992). For example, strong emotional experiences can trigger the release of neurotransmitters, as well as hormones, which strengthen memory; therefore, our memory for an emotional event is usually better than our memory for a non-emotional event. When humans and animals are stressed, the brain secretes more of the neurotransmitter glutamate, which helps them remember the stressful event (McGaugh, 2003). This is clearly evidenced by what is known as the flashbulb memory phenomenon. Watch IT Learn more about flashbulb memories in this brief video. https://youtube.com/watch?v=mPhW9bUI4F0
 
 
 
Reference [13]
Title: Changes in Neurotransmitter Extracellular Levels during Memory ...
Url: https://www.ncbi.nlm.nih.gov/books/NBK3921/
Highlights: These results indicate that glutamate may be one transmitter that conveys the effects of vagal activation on brain systems involved in memory formation.Furthermore, glutamate and glutamate receptors are involved in long-term memory formation as well as in long-term potentiation, a process believed to underlie ...These results indicate that glutamate may be one transmitter that conveys the effects of vagal activation on brain systems involved in memory formation. The ...The release of acetylcholine in different brain areas appears to be involved in processes of attention, detection of novelty or saliency, and during the ...
 
 
Reference [14]
Title: Therapeutics of Neurotransmitters in Alzheimer's Disease
Url: https://journals.sagepub.com/doi/full/10.3233/JAD-161118
Highlights: Along with ACh, glutamate is an ionic form of glutamic acid which is the excitatory neurotransmitter involved in the learning and memory process ...
 
 
 
Reference [15]
Title: Physiology, Neurotransmitters - StatPearls - NCBI Bookshelf
Url: https://www.ncbi.nlm.nih.gov/books/NBK539894/
Highlights: Intriguingly, flux-independent NMDAR signaling has been linked to Alzheimer’s disease while BDNF has been linked to epilepsy, which could make preNMDARs potential therapeutic targets (McNamara and Scharfman, 2012; Dore et al., 2021). Moreover, the synapse-type-specific regulation could potentially be leveraged for drug specificity. While many questions surrounding preNMDARs are yet to be answered, Lituma et al. provide exciting new evidence to unveil the secret life of NMDARs. References - The emergence of NMDA receptor metabotropic function: insights from imagingFrontiers in Synaptic Neuroscience 8:20.https://doi.org/10.3389/fnsyn.2016.00020 - PSD-95 protects synapses from β-amyloidCell Reports 35:109194.https://doi.org/10.1016/j.celrep.2021.109194 -Neurotransmitters are endogenous chemicals that allow neurons to communicate with each other throughout the body. They enable the brain to ...
 
 
Reference [16]
Title: Neurotransmission: The secret life of memory receptors - eLife
Url: https://elifesciences.org/articles/71178
Highlights: THE HIPPOCAMPUS The hippocampal formation is made up of a group of substructures including the hippocampus, the dentate gyrus, and the subiculum all of which are located in the interior of the temporal lobe organized in a similar shape to a letter C. Together these structures represent the main areas of the brain associated with the formation of long term memories.
 
 
Reference [17]
Title: What Happens To The Brain in Alzheimer's Disease?
Url: https://www.alzinfo.org/what-happens-to-the-brain-in-alzheimers-disease/
Highlights: THE HIPPOCAMPUS The hippocampal formation is made up of a group of substructures including the hippocampus, the dentate gyrus, and the subiculum all of which are located in the interior of the temporal lobe organized in a similar shape to a letter C. Together these structures represent the main areas of the brain associated with the formation of long term memories.
 
 
 
Reference [18]
Title: Neurobiology of Memory - an overview | ScienceDirect Topics
Url: https://www.sciencedirect.com/topics/neuroscience/neurobiology-of-memory
Highlights: The hippocampus is one of the most extensively studied brain regions with regard to retrieval mechanisms (as well as acquisition processes). In general, the ...
 
 
Reference [19]
Title: Dopamine and fear memory formation in the human amygdala
Url: https://www.nature.com/articles/s41380-021-01400-x
Highlights: . The amygdala seems to facilitate encoding memories at a deeper level when the event is emotionally arousing.
 
 
Reference [20]
Title: influence of neurotransmitters on memory and learning
Url: https://www.researchgate.net/publication/329773687_INFLUENCE_OF_NEUROTRANSMITTERS_ON_MEMORY_AND_LEARNING
Highlights: . The amygdala seems to facilitate encoding memories at a deeper level when the event is emotionally arousing.
 
 
 
Reference [21]
Title: Protons are a neurotransmitter that regulates synaptic plasticity in ...
Url: https://www.pnas.org/doi/10.1073/pnas.1407018111
Highlights: Another widely held view of prefrontal cortex function is that it encodes task relevant information in working memory (Baddeley, 2003). Many studies have shown greater amounts of prefrontal cortex activity during delay periods in working memory tasks demonstrating prefrontal rehearsal processes leading to the transition of information from short term working memory to long term memory (Wilson et al., 1993; Levy & Goldman-Rakic, 2000). More recent work evaluating greater prefrontal activity during working memory task delays suggest the activity of the prefrontal cortex during these delay periods may not be neural signatures of long term memory encoding, but may actually be top-down signals that influence encoding in posterior sensory and association areas where the actual working memory representations are maintained (Lara & Wallis, 2015). NEUROTRANSMITTERS. The amygdala seems to facilitate encoding memories at a deeper level when the event is emotionally arousing.
 
 
Reference [22]
Title: The Chemistry of Memory - Neuroscience News
Url: https://neurosciencenews.com/memory-rna-neuroscience-8025/
Highlights: Another widely held view of prefrontal cortex function is that it encodes task relevant information in working memory (Baddeley, 2003). Many studies have shown greater amounts of prefrontal cortex activity during delay periods in working memory tasks demonstrating prefrontal rehearsal processes leading to the transition of information from short term working memory to long term memory (Wilson et al., 1993; Levy & Goldman-Rakic, 2000). More recent work evaluating greater prefrontal activity during working memory task delays suggest the activity of the prefrontal cortex during these delay periods may not be neural signatures of long term memory encoding, but may actually be top-down signals that influence encoding in posterior sensory and association areas where the actual working memory representations are maintained (Lara & Wallis, 2015). NEUROTRANSMITTERS. The amygdala seems to facilitate encoding memories at a deeper level when the event is emotionally arousing.
 
 
 
Reference [23]
Title: Neurotransmitters: What they are, functions, and psychology
Url: https://www.medicalnewstoday.com/articles/326649
Highlights: Another widely held view of prefrontal cortex function is that it encodes task relevant information in working memory (Baddeley, 2003). Many studies have shown greater amounts of prefrontal cortex activity during delay periods in working memory tasks demonstrating prefrontal rehearsal processes leading to the transition of information from short term working memory to long term memory (Wilson et al., 1993; Levy & Goldman-Rakic, 2000). More recent work evaluating greater prefrontal activity during working memory task delays suggest the activity of the prefrontal cortex during these delay periods may not be neural signatures of long term memory encoding, but may actually be top-down signals that influence encoding in posterior sensory and association areas where the actual working memory representations are maintained (Lara & Wallis, 2015). NEUROTRANSMITTERS. The amygdala seems to facilitate encoding memories at a deeper level when the event is emotionally arousing.Neurotransmitters are chemical messengers in the nervous system. They influence mood, muscle movement, heart rate, and many other functions.
 
 
 
Reference [24]
Title: 8.2 Parts of the Brain Involved in Memory - Open Text WSU
Url: https://opentext.wsu.edu/psych105/chapter/8-3-parts-of-the-brain-involved-in-memory/
Highlights: The main parts of the brain involved with memory are the amygdala, the hippocampus, the cerebellum, and the prefrontal cortex.
 
 
Reference [25]
Title: Cognitive neuroscience perspective on memory: overview and ...
Url: https://www.frontiersin.org/journals/human-neuroscience/articles/10.3389/fnhum.2023.1217093/full
Highlights: The paper highlights the role of different brain regions, such as the prefrontal cortex in working memory and the hippocampus in declarative memory. The paper ...
 
 
 
Reference [26]
Title: How are memories formed? - Queensland Brain Institute
Url: https://qbi.uq.edu.au/memory/how-are-memories-formed
Highlights: Memory is the reactivation of a specific group of neurons, formed from persistent changes in the strength of connections between neurons.Synaptic plasticity is essentially the process of neuroplasticity occurring at the single-cell level. It is the modification of neural circuitry through the malleability of the individual synapse. There is a large body of research that has elucidated the intricate workings of the synapse, uncovering how it makes modifications to the strength or efficacy of synaptic transmission as a response to stimuli, which may present itself in a myriad of forms). These modifications of synaptic transmission result in stronger or weaker connections between individual synapses, which collectively add up to the effect of neuroplasticity. Research has been able to provide insights into the underlying molecular mechanisms that allow synaptic modification to occur. Key mechanisms such as synaptic vesicle release and recycling, neurotransmitter receptor trafficking, and cell adhesion have all been implicated in synaptic plasticity, and an overview of their roles is given below.
 
 
Reference [27]
Title: What is synaptic plasticity? - Queensland Brain Institute
Url: https://qbi.uq.edu.au/brain-basics/brain/brain-physiology/what-synaptic-plasticity
Highlights: Synaptic plasticity is essentially the process of neuroplasticity occurring at the single-cell level. It is the modification of neural circuitry through the malleability of the individual synapse. There is a large body of research that has elucidated the intricate workings of the synapse, uncovering how it makes modifications to the strength or efficacy of synaptic transmission as a response to stimuli, which may present itself in a myriad of forms). These modifications of synaptic transmission result in stronger or weaker connections between individual synapses, which collectively add up to the effect of neuroplasticity. Research has been able to provide insights into the underlying molecular mechanisms that allow synaptic modification to occur. Key mechanisms such as synaptic vesicle release and recycling, neurotransmitter receptor trafficking, and cell adhesion have all been implicated in synaptic plasticity, and an overview of their roles is given below.Synaptic plasticity is change that occurs at synapses, the junctions between neurons that allow them to communicate.
 
 
Reference [28]
Title: Neurotransmitters: What They Are, Functions & Types
Url: https://my.clevelandclinic.org/health/articles/22513-neurotransmitters
Highlights: - Timmusk, T.; Palm, K.; Metsis, M.; Reintam, T.; Paalme, V.; Saarma, M.; Persson, H. Multiple promoters direct tissue-specific expression of the rat BDNF gene. Neuron 1993, 10, 475–489. [Google Scholar] [CrossRef] - Vashishta, A.; Habas, A.; Pruunsild, P.; Zheng, J.J.; Timmusk, T.; Hetman, M. Nuclear factor of activated T-cells isoform c4 (NFATc4/NFAT3) as a mediator of antiapoptotic transcription in NMDA receptor-stimulated cortical neurons. J. Neurosci. 2009, 29, 15331–15340. [Google Scholar] [CrossRef] - Volpicelli, F.; Caiazzo, M.; Greco, D.; Consales, C.; Leone, L.; Perrone-Capano, C.; Colucci D’Amato, L.; di Porzio, U. Bdnf gene is a downstream target of Nurr1 transcription factor in rat midbrain neurons in vitro. J. Neurochem. 2007, 102, 441–453. [Google Scholar] [CrossRef] [PubMed] - Aid, T.; Kazantseva, A.; Piirsoo, M.; Palm, K.; Timmusk, T. Mouse and rat BDNF gene structure and expression revisited. J. Neurosci. Res. 2007, 85, 525–535. [Google Scholar] [CrossRef] [PubMed]Synaptic plasticity is essentially the process of neuroplasticity occurring at the single-cell level. It is the modification of neural circuitry through the malleability of the individual synapse. There is a large body of research that has elucidated the intricate workings of the synapse, uncovering how it makes modifications to the strength or efficacy of synaptic transmission as a response to stimuli, which may present itself in a myriad of forms). These modifications of synaptic transmission result in stronger or weaker connections between individual synapses, which collectively add up to the effect of neuroplasticity. Research has been able to provide insights into the underlying molecular mechanisms that allow synaptic modification to occur. Key mechanisms such as synaptic vesicle release and recycling, neurotransmitter receptor trafficking, and cell adhesion have all been implicated in synaptic plasticity, and an overview of their roles is given below.Acetylcholine plays a role in muscle contractions, memory, motivation, sexual desire, sleep and learning. Imbalances in acetylcholine levels ...Neurotransmitters are your body's chemical messengers. They carry messages from one nerve cell across a space to the next nerve, muscle or gland cell.The final main group of memory under the category of explicit memory is known as Autobiographical memory. This memory system is made up of both episodic, and semantic aspects of memory and is a collection of memories specifically related to the self. This could be how you look, your height, specific meaningful points in your life, or the general idea of your concept of self. The specific locations where this type of memory are stored and accessed are especially controversial due to the close relationship between autobiographical information and conscious experience. Conway and Pleydell-Pearce (2000) suggested a model describing autobiographical memories as transitory mental compositions stored within a self-memory system containing an autobiographical knowledge base and current goals of the working self
 
 
 
Reference [29]
Title: Parts of the Brain Involved with Memory | Introduction to Psychology
Url: https://courses.lumenlearning.com/waymaker-psychology/chapter/parts-of-the-brain-involved-with-memory/
Highlights: Synaptic plasticity is essentially the process of neuroplasticity occurring at the single-cell level. It is the modification of neural circuitry through the malleability of the individual synapse. There is a large body of research that has elucidated the intricate workings of the synapse, uncovering how it makes modifications to the strength or efficacy of synaptic transmission as a response to stimuli, which may present itself in a myriad of forms). These modifications of synaptic transmission result in stronger or weaker connections between individual synapses, which collectively add up to the effect of neuroplasticity. Research has been able to provide insights into the underlying molecular mechanisms that allow synaptic modification to occur. Key mechanisms such as synaptic vesicle release and recycling, neurotransmitter receptor trafficking, and cell adhesion have all been implicated in synaptic plasticity, and an overview of their roles is given below.
 
 
 
Reference [30]
Title: Role of Neurotransmitters in Memory - JoVE
Url: https://www.jove.com/science-education/18188/role-of-neurotransmitters-in-memory
Highlights: The role of neurotransmitters in memory is multifaceted, influencing the encoding, consolidation, and retrieval of memories through their action ...equipotentiality hypothesis: some parts of the brain can take over for damaged parts in forming and storing memories flashbulb memory: exceptionally clear recollection of an important eventAn imbalance in neurotransmitter levels can lead to memory deficits. For instance, in Alzheimer's disease, reduced levels of acetylcholine, a ...An imbalance in neurotransmitter levels can lead to memory deficits. For instance, in Alzheimer's disease, reduced levels of acetylcholine ...
 
 
 
Reference [31]
Title: Long-Term Plasticity of Neurotransmitter Release - PubMed Central
Url: https://pmc.ncbi.nlm.nih.gov/articles/PMC6238218/
Highlights: equipotentiality hypothesis: some parts of the brain can take over for damaged parts in forming and storing memories flashbulb memory: exceptionally clear recollection of an important event
 
 
Reference [32]
Title: Therapeutics of Neurotransmitters in Alzheimer's Disease - PMC
Url: https://pmc.ncbi.nlm.nih.gov/articles/PMC5793221/
Highlights: Memory is a vital human process. You use it for problem-solving, like answering a question on a test. It helps you plan and navigate through familiar and unfamiliar places. It involves your language development (remembering someone’s name, for example). Your memory also helps with reasoning, like avoiding things that previously caused you harm. As you get older, your memory may not work as quickly as it used to. This is a normal part of aging. But sometimes, underlying conditions can affect how well the parts of your brain responsible for memory function. A healthcare provider can help you if you have any questions about your memory. There are three main types of memory: Sensory memory types represent each of your senses: Advertisement Short-term memory has a limited capacity and duration. You can think of short-term memory as an exclusive VIP club. You can only stay there for a little bit before someone escorts you out.Glutamatergic neurotransmission is an important mechanism involved in learning and memory; therefore it is involved in establishing LTP, which is affected in AD ...
 
 
Reference [33]
Title: The role of serotonin in declarative memory: A systematic review of ...
Url: https://www.sciencedirect.com/science/article/pii/S0149763422002184
Highlights: Globally lowered 5-HT levels impair protein synthesis-dependent memory consolidation. Resulting memory deficits are material specific; object recognition and ...
 
 
 
Reference [34]
Title: Synaptic Plasticity - an overview | ScienceDirect Topics
Url: https://www.sciencedirect.com/topics/psychology/synaptic-plasticity
Highlights: Figure 1. Research in our laboratory has determined that the molecular mechanisms that underlie working memory are antagonistic for short- and long-term memory. We have discovered that while short- and long-term memory requires activation of second messenger kinases, working memory requires phosphatase activity. This molecular switch may represent the means by which information held in working memory is not stored more long-term. Further, this research indicates that drugs which activate protein kinases to improve short- or long-term memory may have detrimental effects on working memory.
 
 
Reference [35]
Title: Neurotransmitter receptors and cognitive dysfunction in Alzheimer's ...
Url: https://www.sciencedirect.com/science/article/abs/pii/S0301008212000214
Highlights: The final main group of memory under the category of explicit memory is known as Autobiographical memory. This memory system is made up of both episodic, and semantic aspects of memory and is a collection of memories specifically related to the self. This could be how you look, your height, specific meaningful points in your life, or the general idea of your concept of self. The specific locations where this type of memory are stored and accessed are especially controversial due to the close relationship between autobiographical information and conscious experience. Conway and Pleydell-Pearce (2000) suggested a model describing autobiographical memories as transitory mental compositions stored within a self-memory system containing an autobiographical knowledge base and current goals of the working self
 
 
 
Reference [36]
Title: Learning and memory under stress: implications for the classroom
Url: https://www.nature.com/articles/npjscilearn201611
Highlights: Stress around the time of learning is thought to enhance memory formation, thus leading to robust memories, stress markedly impairs memory retrieval.
 
 
Reference [37]
Title: Decoding Alzheimer's disease: acetylcholine and dopamine ...
Url: https://academic.oup.com/braincomms/article/8003435
Highlights: The depletion of neurotransmitters in their projecting areas not only impairs the function of affecting regions but also reduces the ...
 
 
Reference [38]
Title: Acetylcholine: Working on Working Memory - Science
Url: https://www.science.org/doi/10.1126/scitranslmed.3003583
Highlights: Alzheimer's dementia is associated with the loss of cholinergic neurons that produce acetylcholine, but drugs that increase acetylcholine levels at the ...
 
 
Reference [39]
Title: Lower Brain Serotonin Levels Linked to Dementia
Url: https://neurodegenerationresearch.eu/2017/10/lower-brain-serotonin-levels-linked-to-dementia/
Highlights: New research suggests serotonin loss may be a key player in cognitive decline, rather than a side-effect of Alzheimer's disease.
 
 
Reference [40]
Title: Neurotransmitters and Memory Aging | USC Gerontology
Url: https://gero.usc.edu/2024/03/22/neurotransmitters-memory-aging/
Highlights: The noradrenaline and dopamine neurotransmitter systems are involved in age-related memory impairment in different ways.
 
 
 
Reference [41]
Title: Neurotrophic Factor BDNF, Physiological Functions and Therapeutic ...
Url: https://www.mdpi.com/1422-0067/21/20/7777
Highlights: BDNF plays an important role in proper growth, development, and plasticity of glutamatergic and GABAergic synapses and through modulation of neuronal ...
 
 
 
 
 
 

---

 
 
 

What happens in the Brain?

Memory isn’t a single "thing" but a process—a dance of neurons, chemicals, and electrical signals. When sensory inputs hit the brain, triggering neurons to fire. These firings form temporary patterns, and if they’re strong or repeated, they get etched in as memories. Chemically, this starts with neurotransmitters like glutamate, the brain’s main excitatory signal.

 
 

Process

 

• Encoding: Initial sensory input sparks activity in areas such as the auditory cortex and visual cortex.
• Consolidation: The hippocampus and amygdala tag it with context and emotion, deciding it’s worth keeping.
• Storage: Over time, it shifts to the neocortex for long-term hold.
• Retrieval: Later cues (repeated sensory inputs) reactivate the pattern.

 
 
 

Key chemicals

 

• Dopamine: Rewards attention, making happy moments stickier.
• Norepinephrine: Heightens alertness, etching stressful memories deeper.
• Acetylcholine: Sharpens focus, helping us tune into subtle cues.

 
 
 

Where Is Memory Stored?

 
 

Short-term Memory

 

Memory isn’t parked in one spot—it’s distributed. The hippocampus is the initial hub, acting like a switchboard for new memories. When sensory inputs hit the brain, the hippocampus binds the inputs from the sensory cortex with the sight (fusiform face area) and emotion (amygdala). Studies—like a 2015 one on rats—show hippocampal neurons firing in sync to encode events.

 
 

Long-term Memory

 
 
After consolidation (often during sleep), memories spread across regions of the neocortex :

• Visual memories: Occipital lobe.
• Auditory memories: Temporal lobe.
• Emotional weight: Amygdala.
• Abstract ties: Prefrontal cortex.

 

This spread explains why brain damage can wipe some memories but not others—there's no single "memory vault." A 2020 study mapped this in humans: cortical networks hold stable patterns years after the hippocampus fades from the equation.
 
 
 

Engram

 

An engram is the hypothetical physical trace of a memory, the idea that a specific neuron group "holds" it. Karl Lashley chased this in the 1950s, slicing rat brains to find it, but concluded it’s not one spot—memory’s too diffuse.


Modern takes are sharper. In 2012, MIT’s Tonegawa team used optogenetics (light to zap neurons) on mice, tagging cells active during a fear memory. Later, they reactivated those exact cells and—bam—the mice froze, reliving the fear. That’s engram territory: a memory tied to a specific neural circuit. Chemically, it’s about strengthening synapses (neuron connections) via proteins like CREB and calcium influxes, making those cells more likely to fire together again.


Engram might be a cluster of neurons in the sensory cortex linked to the fusiform (for the face), cemented by glutamate and dopamine. Over time, the engram adapts—new synapses form, old ones prune—keeping the memory alive but flexible.


However, engrams aren’t the whole story. They’re real—2023 studies keep finding them in mice and hints in humans—but memory’s also dynamic. It’s not just a fixed circuit; it’s a network that shifts with every recall. When the memory is recalled, we are not pulling a pristine file—we are rebuilding it, tweaking the engram with new data. This plasticity, driven by neurochemicals like BDNF (brain-derived neurotrophic factor), lets us track our memory across years.
 

So, memory’s a chemical symphony—glutamate, dopamine, and friends—stored in shifting networks, with engrams as the closest we’ve got to a "memory unit." 

 
The engram—those memory-holding neuron clusters—fits here too. It’s not one chain but a set of them, a stable pattern within the noise. In 2019, researchers zapped engram cells in mice and saw connected chains reactivate, suggesting memory lives in these linked groups. 
 
 

Time and Plasticity

 
 
Over time, the chain evolves. Early on, the hippocampus drives it, chaining sensory inputs into a fresh memory. After consolidation—helped by sleep and proteins like CREB—it shifts to cortical chains, spreading the load. When the memory is recalled, we are not using the exact same chain from the past; it’s a rebuilt version, with neuroplasticity (via BDNF and calcium signals) adding or trimming links. It’s less a fixed chain, more a chainmail—flexible, interconnected, resilient.
 
 
 
 

Memory as Networks and Loops 

 

The Basic Concept

 

If we imagine memory like a chain, each neuron is a link, firing in sequence to pass a signal along. This aligns with Donald Hebb’s famous 1949 idea: "Neurons that fire together wire together." When a specific sound triggers a neuron in the auditory cortex, it excites another in the hippocampus (context), then another in the fusiform face area (recognition), and so on. Chemically, glutamate drives this relay, strengthening synapses (the gaps between neurons) with each pass, forming a pathway.
 

In this sense, memory can feel like a chain—a series of neurons linked by activity. A 2017 study on mice showed this: researchers tracked a fear memory as a sequence of activated cells across the hippocampus and amygdala, lighting up in order when the memory was recalled. 
 
 

Beyond a Simple Chain: Networks and Loops

 

But memory’s not just a straight line—it’s more like a web with chains crisscrossing. Neurons don’t fire in a neat single-file march; they form circuits and loops. Take the hippocampus: it’s not just passing the baton—it’s talking back to the cortex, refining the memory. When the memory is recalled, the brain pings the prefrontal cortex ("this is like yesterday") and amygdala ("this matters"), creating a dynamic network.
 

Chemically, this complexity comes from more than glutamate. Dopamine reinforces the chain’s strength, while GABA (an inhibitory chemical) prunes irrelevant links, keeping the memory sharp. A 2021 study on human brain scans showed memory recall lights up multiple regions at once—temporal lobe, parietal lobe, prefrontal cortex—not a single chain but a chorus of chains firing together.
 
 
 
 

---

Understanding the stress response Chronic activation of this survival mechanism


The sympathetic nervous system functions like a gas pedal in a car. It triggers the fight-or-flight response, providing the body with a burst of energy so that it can respond to perceived dangers. The parasympathetic nervous system acts like a brake.



https://www.health.harvard.edu/staying-healthy/understanding-the-stress-response

Understanding the stress response - Harvard Health

---

Neuroanatomy, Amygdala

Qais AbuHasan; Vamsi Reddy; Waquar Siddiqui.


The circuit has been proposed as a substrate for the human ability to infer the intentions of others from their language, gaze, and gestures (Theory of mind and social cognition),[5] and helps with social interactions.

https://www.ncbi.nlm.nih.gov/books/NBK537102/