A protein synthesis and nitric oxide-dependent presynaptic enhancement in persistent forms of long-term potentiation

Abstract

Long-term potentiation (LTP) is an important process underlying learning and memory in the brain. At CA3-CA1 synapses in the hippocampus, three discrete forms of LTP (LTP1, 2, and 3) can be differentiated on the basis of maintenance and induction mechanisms. However, the relative roles of pre-and post-synaptic expression mechanisms in LTP1, 2, and 3 are unknown. Neurotransmitter release in the expression of LTP1, 2, and 3 was measured via FM 1 -43 destaining from CA3 terminals in hippocampal slices from male Wistar rats (7 -8 wk). No difference in vesicle turnover rate was observed for LTP1 up to 160 min following induction by one train of theta-burst stimulation (1TBS). A presynaptic enhancement was found for LTP2 at 160 min after induction by 4TBS, and for LTP3 at both 80 and 160 min after induction by 8TBS. Inhibition of nitric oxide (NO) signaling blocked both LTP2 and LTP3 maintenance and the associated enhanced release. LTP2 maintenance and its presynaptic expression were dependent on protein synthesis, but not gene transcription. LTP3 maintenance was dependent on both translation and transcription, but like LTP2, the enhanced release only required translation. These data considerably strengthen the mechanistic separation of LTP1, 2, and 3, supporting a model of multiple, discrete forms of LTP at CA3-CA1 synapses rather than different temporal phases.

Dynamics of Multiple Trafficking Behaviors of Individual Synaptic Vesicles Revealed by Quantum-Dot Based Presynaptic Probe

“…After challenging with glycine-induced synaptic potentiation (Gly-SP) protocol (Fig. 3A) [22], the rate of FM 4-64 destaining, which is known to be a reliable indicator for presynaptic release probability [21], [23], was accelerated, indicating that the presynaptic functions were enhanced by the Gly-SP(Fig. S5).…”

Long-term potentiation: Peeling the onion

“…In addition it has been proposed that the properties of LTP change over time. For instance, a widely held model suggests that at some point after the induction of LTP (>1 hour), protein synthesis is required to maintain the potentiation (Johnstone and Raymond, 2011; Reymann and Frey, 2007; Schuman et al, 2006). However it should be noted that, although rarely cited, there have been a number of well controlled studies that have failed to find any dependence of LTP on protein synthesis up to 8 hours after the induction (e.g., (Abbas et al, 2009; Villers et al, 2012).…”

Expression mechanisms underlying long-term potentiation: a postsynaptic view, 10 years on

“…For instance, protein synthesis is thought to be required for the maintenance of LTP at some point (approx. 1 h) following induction [8][9][10]. Although rarely cited, there are also a number of very well-controlled studies that have found no effect of protein synthesis inhibition for up to 8 h following the tetanus [11,12].…”