Natural patterns of activity and long-term synaptic plasticity

Abstract

Long-term potentiation (LTP) of synaptic transmission is traditionally elicited by massively synchronous, high-frequency inputs, which rarely occur naturally. Recent in vitro experiments have revealed that both LTP and long-term depression (LTD) can arise by appropriately pairing weak synaptic inputs with action potentials in the postsynaptic cell. This discovery has generated new insights into the conditions under which synaptic modification may occur in pyramidal neurons in vivo. First, it has been shown that the temporal order of the synaptic input and the postsynaptic spike within a narrow temporal window determines whether LTP or LTD is elicited, according to a temporally asymmetric Hebbian learning rule. Second, backpropagating action potentials are able to serve as a global signal for synaptic plasticity in a neuron compared with local associative interactions between synaptic inputs on dendrites. Third, a specific temporal pattern of activity--postsynaptic bursting--accompanies synaptic potentiation in adults.

Figure 1

Two models for induction of synaptic modifications in the hippocampus. (a) Conventional model for induction of LTP. A ‘strong’ input (large number of synchronously active afferent input fibers) produces a local dendritic depolarization that unblocks NMDA receptors. Synaptically released glutamate in neighboring excitatory synapses, concurrently active with the strong input, can activate the NMDA receptor providing the necessary Ca²⁺ signal for induction of LTP. (b) New model for induction of synaptic modifications based on backpropagating action potentials. In this scenario, postsynaptic action potentials provide a global signal in the neuron, allowing all synapses onto this neuron to be modified, according to their exact timing relative to the postsynaptic action potentials (temporally asymmetric Hebbian learning rule). Postsynaptic bursting signals potentiation in recently active synapses.