In the developing frog visual system, topographic refinement of the retinotectal projection depends on electrical activity. In vivo whole-cell recording from developing Xenopus tectal neurons shows that convergent retinotectal synapses undergo activity-dependent cooperation and competition following correlated pre- and postsynaptic spiking within a narrow time window. Synaptic inputs activated repetitively within 20 ms before spiking of the tectal neuron become potentiated, whereas subthreshold inputs activated within 20 ms after spiking become depressed. Thus both the initial synaptic strength and the temporal order of activation are critical for heterosynaptic interactions among convergent synaptic inputs during activity-dependent refinement of developing neural networks.

Early visual experience is essential in the refinement of developing neural connections. In vivo whole-cell recording from the tectum of Xenopus tadpoles showed that repetitive dimming-light stimulation applied to the contralateral eye resulted in persistent enhancement of glutamatergic inputs, but not GABAergic or glycinergic inputs, on tectal neurons. This enhancement can be attributed to potentiation of retinotectal synapses. It required spiking of postsynaptic tectal cells as well as activation of NMDA receptors, and effectively occluded long-term potentiation (LTP) of retinotectal synapses induced by direct electrical stimulation of retinal ganglion cells. Thus, LTP-like synaptic modification can be induced by natural visual inputs and may be part of the underlying mechanism for the activity-dependent refinement of developing connections.

Induction of long-term potentiation (LTP) of the synaptic connection between two hippocampal glutamatergic neurons in a neural network formed in cell culture resulted in a specific pattern of potentiation at other connections within the network. We found that potentiation propagated from the site of induction retrogradely to glutamatergic or GABAergic synapses received by the dendrites of the presynaptic neuron and laterally to those made by its axonal collaterals onto other glutamatergic cells. In contrast, synapses made by the same presynaptic neuron onto GABAergic cells were not affected, and there was no postsynaptic lateral or forward propagation to other synapses received or made by the postsynaptic neuron. In addition, there was no secondary propagation to synapses not directly associated with the presynaptic neuron. Both induction and propagation of LTP required correlated spiking of the postsynaptic cell as well as the activation of the NMDA subtype of glutamate receptors. Such selective propagation suggests the existence of a long-range cytoplasmic signaling within the presynaptic neuron, leading to a specific pattern of coordinated potentiation along excitatory pathways in a neural network.