Associative Long-term Depression Research Articles

Commissural synapses, but not mossy fiber synapses, in hippocampal field CA3 exhibit associative long-term potentiation and depression

When CA3 commissural afferents received low-frequency (weak) stimuli synchronized with a train of mossy fiber bursts (strong), associative long-term potentiation (LTP) was induced at mixed commissural and associational synapases on hippocampal CA3 pyramidal cells in vitro. In contrast, a weak mossy fiber input did not potentiate when given in phase with commissural/associational bursts. Furthermore, commissural/associational synapses receiving low-frequency stimuli out-of-phase with strong rhythmic mossy fiber input showed associative long-term depression (LTD), whereas mossy fiber synaptic strengths were not depressed when they received weak inputs out-of-phase with a strong commissural/associational input. Thus, both associative LTP and associative LTD can be induced at commissural/associational synapses, but not at mossy fiber synapses.

Associative long-term depression in the hippocampus induced by hebbian covariance

A brief, high-frequency activation of excitatory synapses in the hippocampus produces a long-lasting increase in synaptic strengths called long-term potentiation (LTP). A test input, which by itself does not have a long-lasting effect on synaptic strengths, can be potentiated through association when it is activated at the same time as a separate conditioning input. Neural network modelling studies have also predicted that synaptic strengths should be weakened when test and conditioning inputs are anti-correlated. Evidence for such heterosynaptic depression in the hippocampus has been found for inputs that are inactive or weakly active during the stimulation of a conditioning input, but this depression does not depend on any pattern of test input activity and does not seem to last as long as LTP. We report here an associative long-term depression (LTD) in field CA1 that is produced when a low-frequency test input is negatively correlated in time with a high-frequency conditioning input. LTD of synaptic strength is also produced by activating presynaptic terminals while a postsynaptic neuron is hyperpolarized. This confirms theoretical predictions that the mechanism for associative LTD is homosynaptic and follows a hebbian covariance rule.