Long-Term Potentiation and Long-Term Depression

Synaptic plasticity, the ability of chemical synapses to strengthen or weaken, has long been postulated to be a mechanistic basis of memory. Long-term potentiation (LTP), one form of synaptic plasticity, is defined as a persistent increase in the strength of synaptic transmission, whereas long-term depression (LTD) is the opposite—a persistent decrease in the strength of synaptic transmission. Both LTP and LTD are typically induced artificially with trains of electric stimulation applied to presynaptic neurons, and the resulting change in postsynaptic strength is monitored over time. At the receptor level, there are forms of LTP and LTD that are dependent on the neurotransmitter glutamate activating the N-methyl-d-aspartate (NMDA) receptor. This is important because the NMDA receptor can be thought of as the physical instantiation of the Hebb learning rule. It serves as a coincidence detector, as it becomes active when sufficient input from a presynaptic neuron causes the postsynaptic neuron to fire an action potential. There are also non-glutamate and non-NMDA forms of both LTP and LTD. How LTP and LTD relate to memory in awake behaving animals has been examined three different ways: (a) demonstrations of changes in synaptic physiology due to memory formation (learning), (b) attempts to interfere with memory formation by saturating plasticity using stimulation protocols that induce LTP or LTD, and (c) attempts to block memory formation and LTP or LTD by pharmacological or genetic manipulations. There is a plethora of evidence for LTP- and LTD-like mechanisms overlapping with typical memory formation. Following the detailed characterization of LTP and LTD at the molecular, receptor, synaptic, and behavioral levels in nonhuman animal models, clinical researchers began successfully using noninvasive transcranial magnetic stimulation techniques, which result in LTP- and LTD-like changes, in people with substance use, neurological, and psychiatric disorders.