Cooperation between independent hippocampal synapses is controlled by glutamate uptake.

Localized action of released neurotransmitters is the basis for synaptic independence. In the hippocampal neuropil, where synapses are densely packed, it has been postulated that released glutamate, by diffusing out of the synaptic cleft, may also activate postsynaptic receptors at neighboring synapses. Here we show that neighboring excitatory synapses on hippocampal CA1 pyramidal cells can cooperate in the activation of postsynaptic receptors through the confluence of released glutamate, and that this cooperation is controlled by glutamate uptake. Furthermore, glutamate transporters control temporal interactions between transmitter transients originating from the same axon. Thus, cooperative interactions between excitatory synapses are modulated in space and time by glutamate uptake.