Figure 1
Presynaptic spread of retrograde signals associated with the induction of LTP. (A) Schematic diagram showing the direction of spread of potentiation signals in the presynaptic cytoplasm after induction of LTP at hippocampal synapses in cell cultures (see ref. 137). The site of induction of LTP is marked by the dotted circle. Retrograde signal(s) associated with the induction of LTP (black arrow) may trigger another presynaptic cytosolic signal that propagates throughout the presynaptic cytoplasm (red arrow) and may affect other synapses in close vicinity (black arrow). (B) Three potential mechanisms of retrograde signaling associated with LTP at hippocampal CA1 synapses. Correlated pre- and postsynaptic activity results in postsynaptic Ca2+ influx through NMDA receptors and a cascade of events that lead to three potential forms of retrograde signaling: Secreted factors (e.g., neurotrophins) are released via exocytosis and diffuse across the synaptic cleft to activate presynaptic receptors. Membrane-permeant factors (e.g., NO) directly diffuse from the postsynaptic cytoplasm to the presynaptic cell. Changes in the postsynaptic membrane proteins convey signals in the postsynaptic cytoplasm to the presynaptic cell via their physical linkages to presynaptic membrane receptors. All three forms of retrograde action may modulate presynaptic release machinery, vesicle recycling and refilling, and trigger cytosolic signals (X) for long-range presynaptic propagation of the potentiation signal. Retrograde transport of endocytic vesicles containing internalized neurotrophin–receptor complexes can also propagate the retrograde signal to other parts of the presynaptic neuron.