The search for the molecular and cellular mechanisms of learning and memory has been largely guided by Hebb’s rule, postulated in 1949. This rule proposes that the synaptic connection is strengthened when pre- and postsynaptic neurons are activated simultaneously. In recent years, genetic experiments in adult animals that increased coincidence detection of the NMDA (N-methyl-D-aspartate) receptor, a key molecular switch in the implementation of Hebb’s rule, resulted in improved learning and memory, substantially validating the Hebb’s rule in memory formation in the brain.
The NMDA receptor functions as a molecular coincidence detector, detecting the release of glutamate from presynaptic neurons and the depolarization of postsynaptic neurons. This unique feature makes it essential for the induction of various forms of synaptic plasticity, such as long-term potentiation (LTP) and long-term depression (LTD).
In a groundbreaking study, transgenic mice overexpressing the NR2B subunit of the NMDA receptor in the forebrain showed an increase in the duration of ion channel opening and the amplitude of the NMDA receptor current peak, improving the detection of coincidence signals (TSIEN, 2000). . This improvement in NMDA function resulted in a notable increase in LTP in response to high-frequency stimulation and improved performance on six different behavioral tasks.
These “gain-of-function” experiments demonstrate that increased NMDA receptor-mediated coincidence detection can, in fact, improve both learning and memory in adult animals, convincingly linking Hebb’s rule to learning and memory. (TSIEN, 2000).
Reference :
TSIEN, Joe Z. Linking Hebb’s coincidence-detection to memory formation. Current Opinion in Neurobiology, vol. 10, no. 2, p. 266-273, 2000.
