In neuroscience research, long-term potentiation (LTP) refers to the persistent strengthening of synapses based on recent activity patterns. This phenomenon is widely considered to be one of the main cellular mechanisms of learning and memory. Since it was first discovered in the rabbit hippocampus in 1966, LTP has been a hot topic in neuroscience research.
"Neuroscientists continue to delve deeper into LTP, trying to delineate how memory formation works."
By the end of the 19th century, it was widely recognized in the scientific community that the number of neurons in the adult brain (approximately 100 billion) did not increase with age. This has prompted scientists to explore how memories are formed without the generation of new neurons. Spanish neuroanatomist Santiago Ramón y Cajal proposed at the time that memory might be achieved by strengthening connections between existing neurons. In 1949, Donald Hebb further elaborated on this theory, emphasizing that interconnected cells can undergo growth and metabolic changes.
"Let us assume that repeated active activity tends to induce lasting changes in cells, thereby enhancing their stability."
LTP was first observed by Terje Lomo in 1966 in an experiment conducted in Oslo, Norway. By stimulating synapses in the hippocampus of rabbits, he observed long-term potentiation of early synaptic responses. Subsequently, Timothy Bliss, in collaboration with Lomo, first characterized long-term potentiation in detail in 1973. Subsequent research has continued to explore the basic biology of LTP and attempt to establish a causal relationship between it and behavioral learning.
"LTP manifests itself in different forms in different brain regions, depending on a variety of factors."
NMDA receptor-dependent LTP exhibits multiple properties, such as input specificity, associativity, cooperativity, and persistence. Input specificity means that once LTP is induced at one synapse, it does not spread to other synapses. Associativity refers to the phenomenon that when different pathways are stimulated simultaneously, both can induce LTP. Persistence refers to the fact that LTP can last from minutes to months, which distinguishes LTP from other forms of synaptic plasticity.
Early LTP (E-LTP) is independent of protein synthesis, whereas late LTP (L-LTP) requires both gene transcription and protein synthesis. The initiation of L-LTP involves multiple signaling pathways and requires a contingency of molecular events. The maintenance of L-LTP is associated with sustained protein synthesis, especially increased synthesis of the persistent kinase PKMζ, which is one of the key factors in the maintenance of long-term memory.
The retroactive signal hypothesis states that although the induction and expression of LTP occurs primarily in postsynaptic cells, some evidence suggests that it can also be expressed presynaptically. This process requires some kind of "retrospective messenger" to be transmitted from the postsynaptic cell to the presynaptic cell, which in turn leads to the expression part of the presynapse, such as the enhancement of the probability of neurotransmitter vesicle release.
Exploring the mechanism of long-term potentiation not only provides important clues for us to understand the nature of memory, but also inspires in-depth thinking about emotional and behavioral learning. When we look back on our own learning process, can we find the key to deepening our memory in LTP?