Memory, in general, can be broken down into different forms, being divided according to the functions it serves and the duration for which it holds. Neurobiologically, to qualify as a "memory," an input must both "cause enduring changes in the nervous system, and be affected by emotional and motivational 'sets'" (1).What is meant in that description is that a memory has to have some root in the brain, must induce some change so that the nervous system undergoes some physical change in addition to the ontological change brought about by being in the class of things affected by the input, and must, in turn, affect other forms of behavior. No memories are ever neutral from a behavioral standpoint.
The main functional division among memories is between so-called ""declarative" and "procedural" memories. The former consists of what are termed "episodic" or "semantic" memories. Declarative memories are formed by events, and are brought back in specific contexts and with distinct meanings. "Procedural Memories," on the other hand, include classical conditioning and the acquiring of skills. Central Pattern Generators that form as a result of teaching or practice are procedural memories and they are formed independently of the "I-function." (1).Some scientists refer to this phenomenon as "implicit memory," claiming that "people's behavior objectively indicates memory while they are not aware of it" (2).Animals without the "I-function" can still experience memories, based on their outward behavior. The most studied case of this phenomenon is the Aplysia's gill withdrawal (1).
The most commonly invoked distinction among memories, however, is the split between short and long-term memories. Short term memory immediately follows exposure to an input and decays rapidly, while long term memory has both unlimited capacity and slow decay. The difference between the two lies in types "neural plasticity," the idea that synaptic connections between neurons are malleable. In the former case, no long-term changes occur, while in the latter, there is a fundamental change in neural structure to correspond with the changes in input. In cases of facilitation, where there is less input required to get a desired output, or a case in which "memory" makes the task easier to perform.
Any temporal increase in synaptic potential is the result of changes in the presynaptic transmitter release, although additional messengers are active in inducing long-term change through phosphorylation and the synthesis of new proteins. Some believe that short-term memory may be the product of temporary changes in the shape of neuron spines (3).
The causes of neurobiological changes associated with learning are divided into several types. Habituation refers to the development of pathways among neurons. It comes about through an influx of calcium from the presynaptic side, resulting in a reduction of the membrane potential of the post-synaptic neuron. In Aplysia, both short-term and long-term habituation have been demonstrated, although without repeated inputs, the nervous system can become dishabituated. Habituation weakens synaptic connections, requiring less input to transmit messages, while Sensitization strengthens them. Sensitization involves Serotonin as an "intermediary agent" between neurons and occurs later in development, as well as in classical conditioning. Sensitization seems to be the way in which general patterns are "fixed" in the brain that are resilient to change from various inputs. Neither requires the synthesis of new proteins, which is required in long-term memory (3).
Neurons subjected to repeated inputs can result in Long-Term Potentiation, a phenomenon which allows neurons to fire for long periods of time. It occurs in the hippocampus, as well as in the cerebral cortex, and both are thought to be necessary for memory formation, retention, and recall. In contrast to sensitization and habituation, LTP affects the post-synaptic neuron and uses glutamate as a neurotransmitter, which are received by NMDA receptors. Nitric Oxide, which is different from laughing gas, Nitrous Oxide, functions as a retrograde messenger, and its blockage can interfere with LTP, and, most likely with memory. In addition to LTP, protein synthesis is required to form memories which is, itself, dependent on acetylcholine (1).
Understanding the mechanisms of brain formation and of neural plasticity are important in understanding the aging process, both as the neurological set forms, and as it declines. While conventional wisdom holds that the nervous system is extremely plastic, or malleable, in youth and relatively static as one ages, this is not necessarily the case. While the brain of an infant is more amenable to changes, the reason is that many pathways have yet to form, LTP has not taken effect, nor has it been habituated or sensitized. The neurochemical mechanism involved in regulating plasticity can affect connections between neurons later in life.
The hippocampus is a part of the brain of vital importance for learning and memory, and its biochemical composition is necessary for memories to form. Importantly, it is affected by aging and Alzheimer's Disease. Its role is to recognize spatial relations, as well as to influence the limbic system through communication with the neocortex and the amygdala (4). Interestingly, if the amygdala is removed or rendered inoperable, one can develop Kluver-Bucy syndrome which is characterized by the hypersexuality and personality withdrawal associated with Alzheimer's (1), suggesting that behavioral modifications in Alzheimer's are a result of the inability of the hippocampus to communicate with the amygdala.
Since Protein synthesis and effective use of neurotransmitters are essential for neural plasticity, NMX norepinepherine is a global modulating protein that regulates neural plasticity in the hippocampus and in other parts of the brain. It allows the hippocampus to maintain plasticity throughout development and to allow connections to harden. CREB, a binding protein, has activator and repressor proteins, which are active in learning and in forgetting, respectively. The CREB activator has been demonstrated to be essential in long-term procedural memory in mice, such as the formation of pattern generation. CREB demonstrates that the brain is actively involved in forming new memories and in forgetting, suggesting that neural plasticity is caused by the limbic system as much as it contributes to the brain's self-constituting ability (5).
It is important to remember, however, that not all neurons exhibit plasticity. However, many of those that do are involved in changes in one's cognitive state since any global changes brought about in age are the function of physical or chemical changes in the brain. Understanding what neurons exhibit plasticity, and for what reasons, gives insight into the changes brought about in the aging process.
Alzheimer's Disease (AD) is perhaps the most dramatic manifestation of cognitive decline in the elderly, and its mechanisms illuminate how short and long term, declarative and procedural memories can fail. Given the role the hippocampus plays in memory formation and storage, it should not be surprising that it is adversely affected. Parenthetically, chronic alcohol abuse over time can also induce similar damage to the hippocampus, although not to the same degree (6).AD is thought to be primarily genetic, although environmental factors contribute to its expression. Mutations in the PS-1 gene can interrupt intracellular calcium signaling (7), for example, by affecting NR3A - a subunit of NMDA receptors that, along with glutamate, inhibits excessive calcium uptake (8).Without this communication, it is hard to maintain the pathways forged in the plastic stages. Environmental factors that affect Alzheimer's possible include the lack of Estrogen which helps regulate plasticity and maintain connections among nerves (9).Stress may also contribute to AD since Alzheimer's patients had elevated levels of cortisol, a stress hormone (10).It is not clear whether the high levels of cortisol are causes of brain decline or a product of the difficulty in performing basic tasks.
One study of the hippocampus affected by AD concluded that the largest change in the AD brain is the decrease in the number of synapses and in the area of synaptic contact (11).In aging patients not affected by AD, the size of the synapse increases, the synapse to neuron ratio declines (each neuron does less), and the number of synapses consequently falls. However, in patients with Alzheimer's Disease, the size of the synapses can increase by up to 17% while the number of synapses can decline by as much as 60% in the hippocampus (11).
One possible reason for the increased disassociation among neurons in AD patients may be the disruption of the amyloid precursor protein. Without this protein, plaques develop in the AD brain, effectively blocking communication across synapses. Loss of this protein also causes drops in acetylcholine and glutamate, which are necessary for Long-term potentiation. In addition to disrupting the procedural memory dependent on the hippocampus, AD acts against the formation of new memories and interferes with recall (12).
The number of hypotheses suggesting possible causes of Alzheimer's Disease suggests that there is not a single neurotransmitter, protein, or gene for the disease, and they reveal the myriad factors that go into memory. Common threads in the investigations are the centrality of the hippocampus, the importance of glutamate and acetylcholine, and the importance of neural plasticity in forming and retaining memories. In elderly adults without Alzheimer's Disease, there is great possibility for variation in cognitive ability, both in "crystallized" memory - retention of long-term data, and in "fluid" intelligence - intellectual capacity which likely falls under the heading of procedural memory. While there is a greater decline in fluid intelligence, which is consistent with our understanding of the role of the hippocampus, education can block decline of crystallized intelligence, presumably by maintaining inputs to critical parts of the brain (13).
Much of the research into memory and into aging suggests that the "I-function" is irrelevant to much learning, especially procedural learning, and may even be a function of it since the sense of self that characterizes the "I-function" tends to suffer the deleterious consequences of AD. At the same time, the limbic system is integral to memory, and the limbic system is affected by one's sense of self. Freely chosen steps intended to boost memory, such as educating oneself or reducing stress, themselves suggest that the self is involved in forging memories. While learning and memory storage clearly has a strong neurobiological bent, and does not require us to postulate the "I-function" to explain how it is possible that we remember, but the I-function is at the very least a by-product of the brain's ability to from memories, and can also affect the faculty of memory that helps give rise to it. Our understanding of the self, and of the relationship between the brain and behavior is benefited by studying memory in its formation and its decline.
2)5 March 199: Lecture 18.,
3) Synaptic Plasticity,
4) Brain Mechanisms of Memory ,
5) CREB and Memory ,
6) Learning, Memory, and Emotion ,
7) PS1 Potentiates IP ,
8) Ressearchers Identify Function of Brain Receptor ,
9) Estrogen Could Play Significat Role in Alzheimer's ,
10) Stress and Alzheimer's ,
11) Atrophy of CA1 hippocampal synapses in aging adults ,
12) Geary, James. "Should we just say no to smart drugs?" Time 5 May 1997.,
13) Bachman, Laura. "Aging and Intellectual perfromance among educated older adults ,
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