Department of Pharmacy, Mahatma Jyotiba Phule Rohilkhand University, Bareilly, Uttar Pradesh, India-243006.
Learning and memory are fundamental cognitive processes governed by dynamic neurobiological mechanisms that support adaptation, decision-making, and survival. These processes are mediated by synaptic plasticity, neurogenesis, neurotransmitter activity, and increasingly recognized epigenetic regulations. In recent years, natural compounds have gained prominence for their potential neuroprotective effects in enhancing cognitive performance and combating memory impairment. Centella asiatica, a traditional medicinal herb widely used in Ayurvedic and Chinese medicine, has emerged as a promising nootropic and neuroprotective agent due to its potent antioxidant, anti-inflammatory, and cognition-enhancing properties. Learning and memory are intricate cognitive processes that enable us to acquire, consolidate, and retrieve information. Learning and memory loss impact cognitive functions, often resulting from aging or neurodegenerative diseases. However, memory loss, or the inability to retrieve previously learned information, is a pervasive and debilitating phenomenon that affects millions worldwide.
Learning should not be conceptualized merely as a reaction to environmental stimuli; instead, it is an evolution in that reaction prompted by environmental stimuli. Memory is characterized as the retention of the acquired information, which, naturally, must be amenable to retrieval through some mechanism. The process of learning is essential for the formation of memory traces. Non-Invasive Brain Stimulation (NBS) is a valuable tool for: Studying neuroplasticity: Understanding how the brain adapts and changes, especially in relation to memory and learning. Enhancing memory functions: Improving memory in both healthy individuals and those with brain injuries. Research Applications: Many studies have used NBS to explore learning and memory dynamics in: Brain-injured individuals: Understanding how NBS can help improve cognitive function after brain damage. Healthy individuals: Investigating how NBS can enhance memory and learning capabilities. In short, NBS is a powerful tool for both research and potential therapeutic applications in improving memory and learning [1]. The elucidation of fundamental neuropsychological mechanisms and neurobiological elements, as well as the determination of the applicability of this knowledge in diagnosing and rehabilitating learning and memory impairments across various patient demographics, alongside the appraisal of non-invasive brain stimulation (NBS) for enhancement purposes in cognitively healthy individuals, has constituted the principal aims of investigations centered on NBS in the domains of learning and memory. Motor sequences represent a critical component of numerous daily activities, including writing, typing, verbal communication, knitting, and the performance of musical instruments. The acquisition of motor skills is typically achieved through the mechanism of repetitive practice. Generally, there is a marked enhancement in performance during the initial stages of training, while subsequent practice sessions tend to yield gradual and incremental advancements in proficiency [2]. Brain Regions Involved in Motor Sequence Learning: Cerebellum: Motor coordination, Basal ganglia: Movement control, Supplementary motor area (SMA): Motor planning, Motor and premotor cortices: Motor control. Recently hippocampus also plays a role in motor sequence learning by: Associating temporally discontinuous information: Linking events across time [3]. These brain regions work together to enable motor sequence learning [4]. In studies on amnesia, the hippocampus is typically associated with explicit learning; nevertheless, during sequence learning, hippocampus responses have been observed whether the sequential knowledge was implicit or apparent. Cognitive functioning is made up of a myriad of smaller parts. You can order these parts in a number of ways. Among the most intriguing subjects in modern neuroscience are the definition of learning, the locations of memories, and the kind of changes in the brain that occur during memory formation. The characteristic of learning in neural networks are capacity to encode, store, and retrieve information; learning itself is defined as a long-lasting Behavioral shift resulting from experiences. The ability to learn and recall is essential for individuals to do their daily responsibilities [5]. The hippocampus, prefrontal cortex, striatum, and amygdala are among the interrelated brain regions whose development is hampered by early life stress (ELS) [6]. Among them, the most repeatable results in those exposed to ELS1, include abnormal hippocampal function and reduced hippocampal volume. Previous studies have examined the effects of several types of ELS on mouse Behavioral outcomes, including spatial learning; however, two systematic reviews lacked a meta-analysis and were qualitative in nature. Meta-analysis has not been widely used, even though it is regularly used in therapeutic settings. One way to think of learning is as a process that produces world information, and memory is the capacity to hold onto that knowledge.[7] The brain's hippocampus and temporary lobe are home to long-term memory, whereas the prefrontal cortex is home to short-term memory. Several factors, including stress, aging, and emotions, might impact a person's capacity for learning and memory. These factors help to reconcile conflicting results in mouse preclinical studies. Actually, there are just two meta-analyses that we are aware of that look at how ELS affects rodent behaviour, one of which measures pain sensitivity [8]. Memory is the capacity to hold onto the knowledge that is acquired through the process of learning. The brain's prefrontal cortex contains short-term memory, whereas the hippocampus and temporary lobe contain long-term memory. Learning and memory can be impacted by a number of factors, including stress, aging, and emotions [9]. Age is a factor in the neurodegenerative diseases Alzheimer’s. Clinically the illness is indicated by a decline in learning and memory. When a person has dementia, their ability to learn and remember things is diminished [10]. Learning includes classical and instrumental conditioning, episodic memory, economic decision-making, motor learning. New Framework: A common framework was developed to understand context in learning, leading to a Bayesian model where context is inferred. This approach reveals two key components: Proper learning: Development and updating of memories, Apparent learning: Time-varying changes in memory expression [11]. Learning refers as the ability to change behaviour based on part expression whereas memory is a process of remembering. Memory is classified into two parts i.e. short-term memory and long-term memory. Short term memory remains for shorter period whereas long term memory exists for longer period of time (day to years) [12]. Consolidation is the process through which a newly created memory (short term memory) gets solidified in its original brain circuitry and so become a long-term memory Behavioral tagging has been used to prove that recognition memories enhance in early adult rats, but it has no effect on older rats. Here, we looked at how weak training of spatial object preference affected object location memory consolidation and persistence in young adult and elderly rats when treated with a standardized Centella asiatica related with novelty [13]. Consolidation occurs during sleep and involves the strengthening and reorganization of previously acquired episodic memories. These recollections are contextual in nature, with particular intertwined with more generic attribution like time and location. [14]. We expected that the environment in which a memory is stored would play an important role in the Consolidation process while people slept. We employed a spatial memory task and analysed memory shifts during a 10 hours period that could have included sleep or wakefulness to test this hypothesis. These finding provide more evidences that context – binding plays a critical role in the Consolidation of memories while we sleep [15]. Rats auditory fear conditioning is a common tool for researches interested in learning, memory and emotional responses. In spite of efforts to standardized and improved testing procedures, there remain a wide range of response to test anxiety from one person to the next. Here, we investigated whether behaviour during training and the expression of AMP receptor after long term memory formation in the amygdala could predict freezing during test, with the goal of better understanding which factors can account for this inter- individual heterogenicity. We found substandard individual difference in the ability of outbred male rats to generalize their conditioned fear to novel situation [16]. Synaptic connections between neurons that are part of a memory engram are more common and stronger than connections with neurons not part of the engram. Strengthening of synapses by mechanisms of synaptic plasticity contributes to both the formation of memory engrams and their reactivation during memory recall . Human brain slices: Obtained from surgery (e.g., epilepsy or tumours removal) for electrophysiological recordings. Targeted intracellular recordings: To study human neurons and synapses physiologically [17]. Alzheimer's disease, also known as dementia. A neurodegenerative disorder characterized by: Cognitive impairment, memory loss, poor judgment. Global Impact over 13 million people affected worldwide. Increasing incidence, with 50% of people aged 60-80 expected to suffer by 2030. Causes and Mechanisms: Neuronal damage due to exogenous or endogenous factors, Calcium overload, oxidative stress, and inflammation contribute to disease progression. Treatment Challenges: Neuroprotection is a key strategy, Current treatments (e.g., benzodiazepines, cholinesterase inhibitors) have limitations (side effects, tolerance, short half-life). Novel neuroprotective agents are needed to address this global challenge. [18]. Due to the challenges of nerve regeneration, neuroprotection is a key strategy to the ameliorate Alzheimer diseases. Currently, neuroprotective agents such as benzodiazepines and cholinesterase inhibitors are used clinically for Alzheimer diseases treatment, but their side effects limit their long-term use. For example, benzodiazepines can cause rapid tolerance, and cholinesterase inhibitors have a short half-life. Therefore, the search for novel neuroprotective agents remains a global challenge [19]. Learning and memory are cognitive functions that encompass a variety of subcomponents. These components can be structured in different ways. Declarative Memory. A type of memory that includes: Semantic memory (general knowledge), episodic memory (personal experiences). Key features of it are: Compromised in amnesic individuals, Associated with hippocampus and medial temporal lobe structures. Declarative memory plays a crucial role in our ability to recall and retain information. The brain's capacity to alter its connections and activity in response to internal or external stimuli is known as brain plasticity. In fact, synaptic plasticity facilitates learning and memory processes by altering the structure of spines, dendrites, and axons as well as the intensity and effectiveness of synaptic communication between neurons. Astrocytes are glial cells that round blood arteries and devour synapses. Among their many roles are the control of synaptic processes and the uptake and clearance of neurotransmitters like glutamate and gamma aminobutyric acid. Additionally, microglial cells are essential for regulating neural plasticity. Throughout the brain parenchyma, there is a specific population of tissue-resident macrophages [20]. The brain's powerful processing capacity relies on: Neuronal microcircuits, synaptic connectivity patterns [21]. And types of memory are: sensory memory (brief, unconscious), short-term memory (limited capacity), long-term memory (infinite capacity) [22].
Learning
Learning can be understood as a process that leads to the acquisition of knowledge or skills, while memory refers to the ability to retain and recall that acquired information. Long-term memory is primarily associated with the hippocampus and temporal lobe of the brain, whereas short-term memory is linked to the prefrontal cortex. Several factors such as stress, aging, and emotions can significantly influence both learning and memory [9]. The term ‘learning’ may be defined in various ways, such as "the process of acquiring insight or skills" or "the act of taking lessons and practicing abilities." Definitions typically aim to capture the essential characteristics of a concept or category. Depending on the theoretical framework, definitions may serve causal, functional, or structural purposes and may even be used for explanation, prediction, or evaluation. For a theory of learning to be meaningful, it must clearly explain what "learning" actually means. This helps people understand exactly what the theory is talking about and what it applies to. Sometimes, the meaning of terms in a theory is not directly stated because it’s assumed to be obvious or well-known. But when it comes to learning, it's important to be specific. Some people think that just seeing a change in behaviours is not enough to say that learning has happened. In fact, a change in behaviours is not always necessary or enough to prove that learning took place. Instead, we need to find some kind of internal change in the organism—something inside the brain or body that happened as a result of experience. For example, Lachman (1997) says learning is the process behind behaviours, not the behaviours itself. So, if someone behaves differently, that might be a result of learning—but it’s not the same thing as learning. Other researchers describe this internal change in different ways. Some talk about it in general terms (like "some kind of internal change"), while others are more specific and say it involves mental processes like forming associations between ideas [23]. Because behaviours can be affected by many things besides learning—like mood, tiredness, or outside forces—it’s not always a reliable sign that learning has happened. Learning Types Based on Regularities. Non-associative learning: Behaviour change due to repeated exposure to a single stimulus (e.g., getting used to a loud noise). Classical conditioning (Pavlovian conditioning): Behaviour change due to the relationship between two stimuli (e.g., associating a bell with food). Instrumental learning: Behaviour change due to the relationship between a behaviour and its consequences (e.g., rewards or punishments). Cognitive Definitions of Learning: Focus on mental constructs (knowledge, representations, associations) that cause behaviours changes. These constructs are hard to verify because they're non-physical. In short, learning can be categorized based on the type of regularity or relationship involved, and cognitive definitions focus on the underlying mental changes that drive behaviours [24].
Type of learning
Types of learning are: Associative learning – Classical conditioning, Operant conditioning, non-associative learning – Habituation, Sensitization, priming, reflexes, Observational learning.
Associative memory types classical and operant
Associative memory is the storage and retrieval of information through association with other information. Associative memory involves providing two stimuli close together in time in order to teach a relationship between them, as opposed to habituation and sensitization, when a response to a single stimulus alters as a result of experience. The two primary forms of associative learning are operant and classical conditioning.
Classical conditioning
One important person in the history of associative learning is Dr. Ivan Pavlov. In 1904, Russian physiologist Pavlov got the Nobel Prize in Physiology or Medicine for his research on the physiology of digestion. But his greatest contribution is the discovery of classical conditioning, which even has his name because it is commonly referred to as "Pavlovian conditioning." He made this entirely by accident while researching the canine digestive tract. His research focused on how much saliva was produced by dogs when they were shown food as opposed to non-food items, and he found that, predictably, canines salivated when food was offered to them. But he also saw something odd: the dogs started to salivate before the food was even offered, for instance, when they heard the study assistants walking down the corridor to deliver the food. When consistently combined with the display of food, these audio cues now caused salivation. His most significant contribution, however, is the discovery of classical conditioning, which is so well-known that it bears his name: "Pavlovian conditioning." While studying the digestive system of dogs, he made this completely by mistake. He investigated the amount of saliva generated by dogs when they were shown food versus non-food things and discovered that, as expected, they salivated when food was presented to them. Nevertheless, he also saw something strange: the dogs began to drool before the food was even presented, for example, when they heard the study assistants coming down the hallway to bring the food. These auditory cues now induced salivation when paired regularly with food presentation. Therefore, the only way to distinguish between a conditioned response and an unconditioned response in this case, salivation is the timing for their occurrence, with conditioned responses occurring after the conditioned stimulus but before the unconditioned stimulus. Classical conditioning is the fundamental for many types of fear learning. The phrase "fear memory" refers to a broad category of paradigms where a neutral stimulus and a scary stimulus are associated. Self-report is a useful tool for studying fear in human subject’s research [25].
Operant conditioning
Operant conditioning relies on linking actions to consequences, unlike classical conditioning, which links stimuli. In operant conditioning, behaviours is modified by its outcome, such as a rat pressing a lever for food. Operant conditioning involves learning through consequences, like rewards or punishments, as seen in the lever-pressing rat experiment. The same kind of operant behaviour, meanwhile, may be more recognizable to you if you use positive reinforcement to teach your pet dog new tricks. Your dog will be more likely to repeat a behaviour if you reward him with a treat each time, he performs an action that you find attractive. On the other hand, punishments are acts that make the behaviour less likely to happen again. Negative reinforcement, which involves taking away an undesired stimulus and having the effect of increasing the likelihood of a behaviour, is sometimes mistaken for punishment. The usage of alcohol to reduce social anxiety is a typical illustration of negative reinforcement. The person associates social environments with alcohol consumption because it reduces their anxiety. Positive punishment, in which the conduct is reduced by adding something to the surroundings, is another option. Giving kids additional assignments when they don't finish the allocated work is one example 25].
Non-associative learning: habituation and sensitization
Non-associative learning is type of non-declarative or implicit memory and refers to newly learned behaviour through repeated exposure to an isolated stimulus. A single stimulus may be presented once or several times in non-associative learning. Sensitization and habituation are the two primary forms of non-associative learning. A reduced response to a stimulus after repeated exposure is referred to as habituation. A person who relocates from a small town to a bustling city serves as an illustration. Initially, the noise from the traffic could keep the person wake up at night. After a few days, though, the person may easily fall asleep and no longer notices the sounds. An excessive reaction to a stimulus following repeated presentation is referred to as sensitization. Intense and/or unpleasant stimuli are necessary for sensitization to take place. The constant ringing of a phone becomes increasingly irritating over time [25].
Habituation: When an innocuous stimulus is seen repeatedly, the response becomes less pronounced and eventually vanishes, a phenomenon known as habituation. A habituation reaction happens when stimuli do not cause harm or a sense of reward. Habituation is a type of learning when an organism learns to respond less or not at all to a stimulus after repeated exposures. The organism basically learns to quit reacting to a stimulus that is no longer biologically meaningful. For instance, organism any become accustomed to frequent, loud noises when they realize there will be no negative effects [26].
Habituation: When an innocuous stimulus is seen repeatedly, the response becomes less pronounced and eventually vanishes, a phenomenon known as habituation. A habituation reaction happens when stimuli do not cause harm or a sense of reward. Habituation is a type of learning when an organism learns to respond less or not at all to a stimulus after repeated exposures. The organism basically learns to quit reacting to a stimulus that is no longer biologically meaningful. For instance, organism any become accustomed to frequent, loud noises when they realize there will be no negative effects [26].
Sensitization: The strengthening of the response that occurs after repeated exposure to a potent and damaging stimulus is known as sensitization. The hypersensitivity to a slight touch after an application that might cause harm to the rat is a good illustration of sensitization [5]. Sensitization is non – associative form of learning in which the loudness of a response steadily increases as the stimulus is presented again. In addition to the recurrent stimulus, sensitization is frequently accompanied by an improvement in responsiveness to a whole class of stimuli. In the process of sensitization, a stimulus to one pathway strengthens the reaction in another. Using Aplysia as an example, repeated exposure to a painful stimulus may increase sensitivity to loud noises [27].
Triggering (priming)
Its purpose is to make it easier to recognize inputs, such recently encountered words and objects, by drawing on prior experiences. The cerebral connections created by commonly used events become more noticeable in this way. The word fragment test, which asks a participant to fill in the missing letters of a word, is used to assess how the triggering action affects implicit memory [28].
Observation learning
Observational learning offers benefits in: High-risk situations: Learning from others' experiences without personal risk, Unfamiliar settings: Gaining insights without trial and error. Social Learning Contexts: Playgrounds: Children learn by observing peers, Schools: Observational learning is common in educational settings. Developmental Differences, Children's sensitivity: Highly influenced by others' behaviours [29]. Age-related variations: Differences in processing and using observed information. Computational Modelling: Reinforcement learning: Driven by prediction errors, Prediction errors: Key learning signals reflecting outcome expectations. Research Findings: Age-related differences: Linked to temporal processing variations. Learning rates: Quantify prediction error impact on behaviour [30].
Spatial learning
Memory and spatial learning are assessed using a variety of well-known animal activities. Using either positive environmental variables (like food, water, and shelter) or negative environmental factors (such loudness, bright light, air blast, or submersion in water), these experiments indicate that an animal may learn to navigate a maze. The Morris water maze, the radial arm maze, the win-shift and spontaneous alternation tests in the T and Y mazes, the novel object identification test, and other methods are used in spatial variants to assess spatial learning and memory [31]. Many theories and experiments have been conducted to examine the function of synapses in learning and memory since it was discovered that nerve cells communicate with one another at their synaptic connections. The synaptic plasticity and memory (SPM) hypothesis are the current term used to describe this idea. This mechanism is supported by data from learning-related synaptic changes, environmental enrichment, and visual experience manipulation. [32]. According to cognitive theories, learning is the earning involves mental processes like knowledge creation, acquisition, organization, and retrieval. Constructivism views learning as a personal construction of knowledge based on experiences. Learning capacity is shaped by prior knowledge and understanding. Knowledge processing involves mental activities like coding, rehearsal, and memory storage. According to constructivism, learning is a subjective process of building knowledge from experiences [33].
Emotion and learning
Enhance cognition: Improve information processing, decision-making, and creative problem-solving. Boost memory: Serve as strong retrieval cues for long-term memory and enhance recall. Increase motivation: Strengthen motivation to put effort into learning tasks [34]. Positive emotions enhance cognitive processes crucial for learning, such as information processing, decision-making, and creative problem-solving. Research shows that pleasant emotions improve memory, motivation, and learning outcomes. Emotions play a significant role in learning, with positive emotions boosting cognitive functions and motivation [35].
New Evidence on Emotion's Influence on Learning and Memory
The impact of emotion on learning and memory has been the subject of numerous recent studies. Emotional impacts on learning are still up for debate, despite the fact that it is well recognized that emotions have an impact on memory recall and retention. Research shows positive emotions enhance learning and academic success through self-motivation and satisfaction. Confusion, a state of cognitive dissonance, can stem from conflicting information and impact emotions; the former is heightened while the latter is triggered at a low level of anger or annoyance. Motivated pupils attempt to gain new understanding by putting in greater cognitive effort in response to their bewilderment. Learning is enhanced when this is explained in greater detail. Furthermore, stress is a negative emotional state that, depending on its intensity and duration, can either improve or worsen memory and learning [36].
Understanding the factors that influence emotional effects on learning and memory is crucial
In the section above, neuroimaging methods for analysing how the brain reacts to emotional stimuli during WM processing that results in LTM were discussed. The experimental design and suitable technique should take into account the six important elements that are presented in this section.
Individual Differences
Numerous studies have documented a variety of individual variances in emotional processing as well as a multitude of factors. These consist of sex, intellectual capacity, and personality traits. Furthermore, personality factors like neuroticism and extraversion, as well as sex hormones, seem to affect how people react to emotional stimuli and how they interpret emotions. Reducing erroneous results due to individual differences can be achieved by balancing experimental cohorts by sex and doing appropriate screening with psychological testing [37].
Age-Related Differences
According to studies, older persons have a larger acquaintance with the psychological stress and emotional experiences than younger adults do. As a result, they process emotions more positively and have better emotional control [38].
Memory research
Baddeley (1997) reports on the work of Tulving in the development of a memory systems model where there are multiple dissociable memory systems, each with its own unique type of code. These memory systems are perceptual, procedural, semantic, and episodic. Tulving’s model has been associated with considerable application of memory function to the education and learning process. Many researchers have distinguished among various types or forms of memory. For instance, recalling someone’s name is different from recognizing it and visual memories differ from auditory memories. Recently, many researchers have distinguished between recollection of everyday experiences, explicit memory, and non-conscious effects of past experiences on subsequent behaviour, implicit memory. Although concepts of memory systems are still evolving, converging evidence from psychology and neuroscience points toward at least five major systems which include episodic memory, semantic memory (together referred to declarative memory), perceptual representation system, procedural memory, and working memory [39]. As reported by Baddeley, Tulving explained in 1983 how the episodic memory stem is responsible for the explicit recollection of incidents that occurred at a particular time and place in one’s personal past. Damage to the inner parts of the temporal lobes, including the hippocampal formation, greatly impairs the acquisition of new episodic memories. Individuals with amnesic syndromes produced by damage to the medial temporal region invariably have serious impairments of episodic memory. They are unable to remember ongoing events in their day-to-day lives and perform poorly on laboratory tests that require episodic memory [40].
Memory consolidation
Memory consolidation begins with a gene expression-dependent phase lasting hours or days, known as cellular consolidation. The initial phase of memory storage, cellular consolidation, is fragile and relies on gene expression are not fully processed and stable after this initial phase: although considered consolidated according to molecular interferences, these memories are still undergoing a great deal of processing that culminates with a network rearrangement that is accompanied by a decline in the critical role of the hippocampus [41]. If the hippocampus is inactivated or lesioned during this phase, the memories are lost. This process lasts for weeks in animals and up to years in humans and it is known as the system of consolidation. [42]. Memory Formation and Engram Cells: Learning alters neuron physiology: Creating memory traces that encode experiences, Engram cells: Specific neurons storing memory traces, Memory traces: Molecular and cellular changes encoding experiences. Consolidation and Memory Storage: Consolidation: Stabilizing memories after acquisition, Neural circuits and neurons: Collectively forming the memory engram, Memory engram: The overall collection of molecular and cellular memory traces [43].
Type of memory
Memory plays a vital role in day-to-day living. It reduces hazards, preserves experiences, and enables us to engage with the world and other people. Memory formation is broken down into three primary steps by neuroscientists: The first is encoding, which is the process of first registering and gathering data. The first is encoding, which is the initial registration and data collection procedure. The technique of storing encoded data in memory to maintain it and produce a continuous record of it is the second element. The last stage of memory formation is called retrieval, and it is defined as recalling or reminding oneself of the store's facts. According to the type of knowledge and the amount of time that has passed, memory is usually classified into two groups. Depending on how long it lasts, memory is categorized as either short-term or long-term. Long-term memory can be classified as either declarative or non-declarative. Declarative memory is a type of memory system that includes events or facts and a conscious element. Four primary categories can be used to analyse non-declarative memory: priming, Associative learning, including classical conditioning (Pavlovian conditioning), non-associative learning habits and sensitivities, and abilities and habits, like riding or driving [44]. Types of memory are: Sensory memory, short term memory and long-term memory. And short-term memory types are: explicit memory and implicit memory. Explicit memory types are: episodic memory and semantics memory.
Sensory memory: iconic memory
Sensory memory is the capacity to temporarily store the enormous amounts of information that people encounter on a daily basis [45]. There are three different kinds of sensory memory: echoic, iconic, and haptic. Information obtained through sight is stored in the iconic memory, information obtained through aural stimuli is stored in the echoic memory, and information obtained through touch is stored in the haptic memory. The ability to temporarily store the vast amounts of information that people come into contact with on a daily basis is known as sensory memory. The majority of scientific studies have been on iconic memory; there is relatively little data on echoic and haptic memory. Thus, providing iconic memory as a paradigm of sensory memory is adequate for an introductory review given the objectives of this essay and the fact that it is intended for a higher education audience [46].
Short-Term Memory
Temporary storage: Holding information for processing. Information modification: Manipulating information for cognitive tasks. Executive function: Overseeing complex cognitive subroutines Information transfer: Between sensory storehouses, short-term memory, and long-term memory. Cognitive activities: Learning, thinking, comprehension, and problem-solving. Working memory: A mechanism for temporarily storing and modifying information. Functions of Short-Term Memory: Processing information: From sensory data and long-term memory. Generating new information: Through reasoning and deductions. Organizing and overseeing: Executive system managing complex cognitive subroutines. Importance of Short-Term Memory: Critical for learning: Temporarily storing and processing new information. Essential for cognitive tasks: Thinking, comprehension, and problem-solving. Key component of executive function: Overseeing and managing cognitive processes [46].
Long- term memory
Declarative memory includes episodic and semantic memory, involving conscious recall. Implicit memory involves unconscious retention of skills and aptitudes. Types of Long-Term Memory: Declarative (Explicit) Memory. Episodic memory: Recalling specific events and experiences. Semantic memory: Storing factual knowledge and general information [48]. Non-Declarative (Implicit) Memory. Procedural memory: Skills and habits. Associative memory: Learning through associations. Non-associative memory: Habituation and sensitization. Priming: Activating certain associations or memory [46]. Individuals within a population transmit information primarily through social learning, which is the ability to learn from others, as long as the information is retained long enough for others to replicate it. Additionally, when combined with the capacity to gather data from the vast majority of people in a population [47]. Certain characteristics and habits may be passed down from one generation to the next as a result of long-term memory of socially taught features, giving rise to a new kind of heredity called cultural inheritance. The growth of local cultural customs that can last for many generations can then be promoted by this [48]. Therefore, it is crucial to conduct study on long-term social memory, which is the preservation of socially learnt traits across time [49]. Because they can remember familiar, non-kin people after a lengthy period of time—sometimes even decades—mammals are known to develop long-term social memory (LTSM). A strong social memory was thought to be advantageous, particularly in fluid social systems, and this LTSM appears to be situated in the hippocampus [50].
Explicit memory/declarative memory
Explicit memory is the term used to describe information that can be consciously recalled. Semantic memory and episodic memory are the two Flavors of declarative memory. As shown below, factual knowledge is preserved in semantic memory, whereas personal experiences are stored in episodic memory. Declarative memory's brain process has been thoroughly investigated in both humans and animals [51]. This hypothesis holds that learning and assimilating new knowledge depend heavily on the hippocampus and other medial temporal lobe structures, which face the inner portion of the temporal lobe. The process of solidifying memories after learning, like as you sleep, is called consolidation. According to research on individuals with significant MTL injury, these MTL structures may not only be involved, but also crucial for idiosyncratic (unpredictable) learning and connection bits of information. have significant effects on hippocampus function and declarative memory, as does the hormone estrogen (greater declarative memory is linked to higher levels) [52].
Non- declarative /implied memory
Long-term memory stores information for extended periods, categorized into declarative and non-declarative types. Information retained for long periods is known as long-term memory, which includes explicit and implicit memory. Implicit memory encompasses all unconscious memories as well as particular abilities or skills. There are four types of implicit memory: procedural, associative, non-associative, and priming. Non-declarative, or implicit, memory is one type that enables the development of habits and motor skills. Examples of previously taught skills and knowledge that are said to as unconscious are riding a bike or operating a motor vehicle. With experience, many cognitive, motor, and perceptual skills begin to be stored in implicit memory after first being stored in explicit memory. Despite having significant memory loss for people and events, patients with substantial damage to the hippocampus and temporal cortex can nevertheless read music, play the piano, and lead the choir without losing track of their actions. Nine Triggering, procedural, associative, and non-associative memory are the four subgroups of non-declarative memory that are identified [53]. on-declarative (implicit) memories refer to unconscious learning through experience, such as habits and skills formed from practice rather than memorizing facts; these are typically acquired slowly and automatically in response to sensory input associated with reward structures or prior exposure with in our daily lives [54].
Semantic memory
Declarative memory includes episodic and semantic memory, enabling concept representation and manipulation. Human language abilities facilitate sharing and combining conceptual knowledge. Therefore, as Binder and Desai show, “humans use conceptual knowledge for much more than merely interacting with objects. All of human culture, including science, literature, social institutions, religion, and art, is constructed from conceptual knowledge” [55]. Semantic memory in adults has typically been viewed as a relatively fixed reposition of acquired facts about the word, concepts, and symbols. This fixed concepted of sematic memory has been heavily contested in recent decades, with researchers proposing an adaptive system that can adapt to changing circumstances and tasks, as well as perceptual and sensory motor input from the environment. This paper reviews classical and contemporary computational models of semantic memory under the broad categories of network (free associated – based), feature (property generation forms – based) and distributional semantic (natural language corpus- based) models2; discusses knowledge representation (localist vs. distributed representation) of learning and memory (error – free/driving learning [56].
Episodic memory
The ability to precisely and clearly recall distinct experiences or events is known as episodic memory. Among memory systems, episodic memory is unique due to its clear association with time and a feeling of self. People frequently consult a neurologist for a clinical assessment of a memory problem when they struggle to recall information in this clear, declarative way. Three steps make up episodic memory conceptually: encoding, consolidation, and retrieval. While "encoding" refers to the allocation of cognitive resources to the processing of information via attentional mechanisms, "consolidation" refers to the mental archiving of knowledge in a way that makes later retrieval easier. The process of remembering this knowledge is referred to as "retrieval." [57].
Procedural memory
Procedural memory directs behaviour subconsciously, retrieving executive and motor abilities. Procedural learning automates complex tasks through repetition, enhancing performance. Procedural memory: Retrieving executive and motor abilities. Procedural learning: Developing rote skills through repetition. Automation: Enhancing performance through practice [46]. The portion of memory involved in retrieving the motor and executive abilities required to complete a task is known as procedural memory. This executive system, which typically operates subconsciously, directs action. Procedural memories are automatically retrieved when needed to carry out intricate processes involving intellectual and physical skills. [58].
Working memory
Working memory impairment are one of the several neurobehavioral changes linked to traumatic stress disorder. Despite the therapeutics importances, chronic or reactive working memory deficiencies have not been thoroughly explored in rodent models of traumatic stress disorder [58]. In this study, male and female rats are subjected to foot shock, which induces a posttraumatic stress state, and their ability to remember odor pairs associated with trauma is tested using the odor span task. By 3 weeks following the acute stress, animals who have been subjected to foot shock show signs of developing chronic deficiencies in working memory. Working memory performances in male’s rats was further reduced after being exposed to a trauma-paired olfactory cue may also be predicated by anxiety- like behaviours associated with the PTSD-like phenotype [59]. Studies in which parietal areas were stimulated by researchers have produced somewhat conflicting finding. Both tDCS and TMS investigations have shown this to be true. While some TMS studies reports enhancement STM [60].
Temporal memory
The ability to learn, store, and retrieve knowledge about distinct personal experiences that arise in day-to-day living is known as episodic memory. These memories often include details about the event, time, and location. Recollections typically encompass specifics about the incident, including context [61].
Extending memory
These changes suggest that our understanding of memory has to be rethought. The finest example of this discrepancy is the way we use the terms "memory" and "memories" differently. In general, recollections of past events are called "memories" and are considered to be more representational and subjective. However, the word "memory" is now used to refer to the generic storage of information, which includes information stored in digital devices, DNA, and neurochemical processes. The widespread belief that memory is individualized, subjective, and static is very different from modern science [22].
Hippocampus’s role in learning and memory
The importance of the temporal lobe and hippocampus structures for declarative/associative memory is demonstrated by research in neuropsychology and neuroanatomy. The hippocampus, located in the temporal lobe and a crucial part of the limbic system, plays a crucial role in the formation, consolidation, and recall of episodic memories. 18. The hippocampus is a tri synapse that consists of the dentate gyrus (DG), cornu ammonia 3 (CA3), and CA1 components. Cajal published his famous diagram of the hippocampus formation's main cells, connections, and impulse traffic flow [62].
Epidemiology
Dementia risk can be reduced by addressing factors like eyesight loss, high cholesterol, and social isolation. Midlife interventions may have the biggest impact on preventing dementia later in life. 45% of dementia cases: Potentially preventable or delayed. 14 risk factors: Including new factors like failing eyesight and high LDL cholesterol. Midlife interventions: Most effective in reducing dementia risk [63].
Etiology
Different diseases of learning and memory
The primary and most typical presenting sign of Alzheimer disease is episodic short-term memory loss, with long-term memory remaining relatively intact. Alzheimer disease is the most prevalent form of dementia. Impaired problem-solving, judgment, executive functioning, disorganization, and lack of motivation follow short-term memory impairment, which leads to issues with multitasking and abstract thought [64].
Dementia
It is among the most prominent and common memory impairments. The cognitive processes have a declining and especially connected to forgetting. These people struggle to finish basic chores, demonstrating their incapacity for life’s demands.
Delirium in memory disorder
Delirium is an abruptly confused state characterized by changes in mental abilities. Disorientation results from the person ‘s inability to pay attention. In this context, delirium and dementia are mutually exclusive.
Encephalopathy
Major neurological alterations that alter how the brain function can result from brain inflammation. Seizures and fits can result from a severe lack of brain impulses. This goes along with the delirium like condition. The main cause of encephalitis is viruses. When specific neurological conjugation, such as Parkinsonism, weakness, the inability to maintain daily assessment functioning, tremors and vertigo are present it is interrupted. This can also be combined with the typical headache symptoms.[64]
Vascular
Vascular dementia that results in less blood flowing to the cerebellum and cerebral regions is the causes of this dementia. this form of dementia can be brought on by strokes and hand trauma, Planning and comprehending issues are evident.
Lewy bodies
The growth and accumulation of aberrant protein types known as Lewy bodies is specifically linked to the particular form of dementia. These aberrant accumulations memory space that results in declining brain functions.[65]
Frontotemporal
The frontal and temporal cortex of the brain are affected by these types of dementia. Which is the most prevalent variety. Typically, this kind of dementia shrinks brain nerve cells by affecting them. Although a usually affect people between the ages of 45 and 60, younger people can also have it. This is connected to aphasia, a condition marked by speech impairment. this could cause them to loss their anger easily and say improper things at the wrong time [65].
Alzheimer diseases
Alzheimer's disease impacts cognitive function, causing memory loss, language difficulties, and behavioural changes. The number of people living with AD in the US is projected to rise to 13.8 million by 2060. 1. 6.7 million: People 65+ living with AD in the US (2023).2. 13.8 million: Projected number of people with AD in the US by 2060. Clinical Manifestations: Cognitive decline: Memory impairment, aphasia, dysarthria. Behavioural changes: Personality changes, executive dysfunction [66].
Nutritional deficiencies
Vitamin B12, Folate and Omega-3fatty acids are essential for neuronal function.
Pathophysiology of learning and memory
Complex cognitive processes involving a variety of brain circuits, neurotransmitters, and chemical reactions are involved in learning and memory. They depend on how well information is encoded, stored, and retrieved by the brain. The pathophysiology of learning and memory loss is caused by changes in the structure and function of neural networks, which can be brought on by age, brain trauma, neurodegenerative illnesses, or neurochemical imbalances. It has been proposed that Aβ can regulate ion channel activities and is necessary for neuronal health. Aβ is created by the progressive cleavage of the necessary membrane protein amyloid precursor protein (APP). NFTs are filamentous inclusions in the degenerative neurons of AD and other tauopathy neurodegenerative disorders [67].
Physiology of learning and memory
Several research covering a wide range of topics. The cellular and molecular processes that underlie brain development memory and acquisition have been the subject of extensive study. Both neural activity (neuronal firing) and neuronal plasticity (the growth of new axons, dendrites and synapses) are central to current theoretical frame work for learning and memory [68]. The neural mechanisms by which we take in new information and store it in memory are still a mystery, as is the brain’s structure with respect to learning and forgetting. The phenomenon of long-term potentiation has recently been proved to be associated with the establishment of new synapses and it is widely believed that long term depression is one of the best and most accepted models of the learning and memory formation [69]. Stress and cognitive processes are regulated at multiple level by activating different parts of the brain. Despite the facts that a complete picture cannot yet be established, we now have a fundamental understanding of the brain regions involved in stress reactions and cognitive functions, their neuroanatomical and neurofunctional linkages and the participation of neuro messengers, injury to certain parts of the brain such as the hippocampus, amygdala, medical septum, neocortex can have long lasting effects on Synaptics efficiency, impairing learning and memory [70].
Pharmacotherapy
Classification Of Drugs Affecting Learning and Memory-
Nootropics influence the central nervous system's neuronal metabolism to improve cognitive processes. The classification of nootropics varies, with some distinguishing between cognitive enhancers and brain metabolism boosters. Key Aspects: Definition: Nootropics stimulate cognitive processes like memory and learning. Etymology: Derived from Greek words "nöos" (think) and "tropein" (direct). Classification: No standard method, varying definitions and categorizations. Types of Nootropics: Cognitive enhancers: Improve memory, learning, and focus. Brain metabolism boosters: Enhance neuronal function and energy [71].
Cognitive enhancer: Piracetam, Modafinil.
Cholinergic drugs (Increases Acetylcholine): Donepezil, Rivastigmine.
Glutamatergic drugs: Memantine.
Dopamine drugs: Levodopa, Bromocriptine.
GABAergic drugs: Benzodiazepine (diazepam, lorazepam) [71].
Mechanism of learning and memory
Without directly binding to receptors or releasing neurotransmitters, nootropics increase the amount of glucose and oxygen that reach the brain, have ant hypoxic effects, and protect brain tissue against neurotoxicity. They also encourage the metabolism of phospholipids in neurohormonal membranes and have a beneficial impact on the synthesis of proteins and nucleic acids in neurons. Some nootropics have been found to improve erythrocyte flexibility, have an anti-aggregation effect, and affect the elimination of oxygen free radicals. This improves the rheological properties of the blood and boosts blood flow to the brain. Even though these medications have metabolic action, most nootropics require some time to start making an effect after a single administration. To improve brain metabolism, they need to be able to pass through the blood-brain barrier [72].
Memory enhancement
Memory enhancement is the process of improving memory in both healthy and diseased people by using behavioural, technical, or pharmaceutical means. In addition to focusing on categories like short- and long-term, declarative, non-declarative memory, etc., they also target the three primary components of the memory: encoding, storage, and retrieval. Some treatments for neurodegenerative diseases target the underlying illness, while others address the symptoms of memory loss. Different memory functions can occasionally be pushed in opposite ways by drugs that influence many physiological systems, such as the glucocorticoid, endocannabinoid, norepinephrine, dopamine, and serotonin systems. For instance, these drugs may improve memory creation while worsening retrieval, or vice versa. Therefore, deciding which functions need to be upgraded and then choosing the best strategy are crucial [73].
Treatment of learning and memory
The drugs which are used to enhance learning and memory are called nootropics. Another name of nootropics is smart drugs. There drugs help to improve and enhance memory, thinking, learning and alertness of an individual suffering from dementia. The mechanism of action of nootropics is alteration in availability neurochemicals supply of brain and enhancement of oxygen supply of brain or by the stimulation of nerve growth in brain [74]. Cognitive Training: Targeted exercises to improve memory, attention, and processing speed. Memory Aids: Tools like calendars, reminders, and notes to support memory. Compensatory Techniques: Strategies to work around memory deficits, such as using mnemonics. Pharmacological Interventions: Medications like cholinesterase inhibitors for Alzheimer's disease. Lifestyle Modifications: Regular exercise, social engagement, and cognitive stimulation. Therapies: Cognitive Behavioral Therapy (CBT): Helps individuals cope with cognitive difficulties. Memory Rehabilitation: Tailored programs to improve memory function. Neuropsychological Interventions: Targeted therapies to address specific cognitive deficits. Emerging Approaches: Neuroplasticity-Based Interventions: Techniques to promote neural adaptation and reorganization. Brain Stimulation: Methods like transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). Lifestyle Factors: Exercise: Regular physical activity supports cognitive health. Social Engagement: Social interaction and connection promote cognitive well-being. Cognitive Stimulation: Engaging in mentally stimulating activities [75]. Education and midlife and late-life cognitive stimulation.
Diagnosis
Clinical diagnosis
Taking a history (onset, course and functional effect of symptoms)
Medical and family history.
Cognitive assessments
MMSE stands for Mini- Mental State Examination.
Moca stands for Montreal Cognitive Assessment.
WMS or Wechsler Memory Scale.
Neuropsychological testing for attention, memory and executive function.
Imaging Methods
MRI: Identifies structural alterations such as atrophy of the hippocampus.
PET scans: To identify tau or amyloid buildup in Alzheimer’s disease.
Biomarkers: Examination of the tau protein and Aβ42 in cerebrospinal fluid
Biomarkers based on blood are a new field [76].
Latest drugs for learning and memory [77,78,79]
CONCLUSION
Learning and memory are fundamental cognitive processes that enable organisms to acquire, store, and retrieve information essential for adaptation and survival. These processes are complex and involve multiple brain regions, primarily the hippocampus, prefrontal cortex, and amygdala, each contributing uniquely to different types of memory such as spatial, declarative, and emotional memory. Neurotransmitters, synaptic plasticity, and molecular pathways, including long-term potentiation (LTP), play crucial roles in strengthening neuronal connections that underlie memory formation. Moreover, recent advances in neuroscience have highlighted the influence of epigenetic mechanisms, such as DNA methylation and histone modification, in regulating gene expression necessary for memory consolidation and retrieval. External factors like stress, aging, and neurodegenerative diseases can impair learning and memory, often by disrupting synaptic function and promoting oxidative stress. Conversely, certain neuroprotective agents, environmental enrichment, and cognitive training can enhance these processes. Understanding the intricate biological and molecular basis of learning and memory not only provides insight into brain function but also offers potential therapeutic strategies for cognitive disorders. Continued research in this field, especially in areas like neurogenesis and epigenetic modulation, holds promise for developing interventions to maintain and improve cognitive health throughout the lifespan.
REFERENCES
Madhuri*, Kamal Kishore Maheshwari, Epidemiology, Etiology, Pathysiology, Physiology, Pharmacotherapy, Treatment and Diagnosis, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 6, 3502-3524. https://doi.org/10.5281/zenodo.15719429
10.5281/zenodo.15719429
