The expression of long-term potentiation: reconciling the preists and the postivists

Abstract

Long-term potentiation (LTP) of excitatory synaptic transmission in the hippocampus has been investigated in great detail over the past 40 years. Where and how LTP is actually expressed, however, remain controversial issues. Considerable evidence has been offered to support both pre- and postsynaptic contributions to LTP expression. Though it is widely held that postsynaptic expression mechanisms are the primary contributors to LTP expression, evidence for that conclusion is amenable to alternative explanations. Here, we briefly review some key contributions to the ‘locus’ debate and describe data that support a dominant role for presynaptic mechanisms. Recognition of the state-dependency of expression mechanisms, and consideration of the consequences of the spatial relationship between postsynaptic glutamate receptors and presynaptic vesicular release sites, lead to a model that may reconcile views from both sides of the synapse.

The related neuronal endosomal proteins NEEP21 (Nsg1) and P19 (Nsg2) have divergent expression profiles in vivo

“…These processes are dependent on the induction of long term depression (LTD) and long term potentiation (LTP) (Malenka & Bear, 2004; Sweatt, 2016). In LTP, AMPA receptors are recruited to the synapse and inserted into the membrane (Jurado, 2014; MacDougall & Fine, 2014). At the molecular level, NEEP21 has been shown to facilitate recycling of the AMPAR subunit GluR2 in hippocampal slices, and reduction of NEEP21 levels leads to a decrease in the surface levels of GluR2 containing synapses (Steiner et al, 2005).…”

Vesicular Synaptobrevin/VAMP2 Levels Guarded by AP180 Control Efficient Neurotransmission

“…In agreement with this interpretation, slices from AP180 À/À mice showed increased paired-pulse facilitation (PPF) of fEPSPs ( Figure 3D), a parameter for short-term presynaptic plasticity (Catterall and Few, 2008). Short-term plasticity (STP) induced by theta burst stimulation, another well-established parameter of presynaptic plasticity (Catterall and Few, 2008;Zucker and Regehr, 2002), was likewise increased (Figures 3E and S2C), whereas postsynaptic long-term potentiation (LTP) (Bliss and Collingridge, 2013;MacDougall and Fine, 2014) was unchanged ( Figures 3E and S2C). The latter is consistent with the exclusive presynaptic localization of AP180 ( Figures 1A-1D) and the absence of significant alterations in postsynaptic GluR1 levels (AP180 À/À = 98% ± 24% of WT, N = 3).…”

Structural Components of Synaptic Plasticity and Memory Consolidation

“…Interestingly, even in the mature hippocampus, .75% of all spines are small dendritic spines with head diameters of ,0.6 mm. These small spines are more prone to rapid formation and elimination depending on age and the conditions of activation Harris 2007, 2011;Macdougall and Fine 2014).…”

“…Within minutes following the induction of LTP, silent synapses, which are commonly found in the developing nervous system, undergo activation by the insertion or functional modification of AMPA receptors (AMPARs) (Edwards 1991;Isaac et al 1995;Liao et al 1995;Durand et al 1996;Petralia et al 1999;Malinow et al 2000;Malinow and Malenka 2002;Groc et al 2006;Hanse et al 2009;Macdougall and Fine 2014). Initially, potentiation (or depression) can be sustained by these changes in glutamate receptor properties and composition, but longerlasting potentiation (or depression) involves structural alterations in spines and synapses in both the "immature" (Engert and Bonhoeffer 1999;Maletic-Savatic et al 1999;Ostroff et al 2002;Lang et al 2004;Matsuzaki et al 2004;Nagerl et al 2004Nagerl et al , 2007Kopec et al 2006) and "mature" hippocampus (Van Harreveld and Fifkova 1975;Trommald et al 1996;Chen et al 2004;Nagerl et al 2004;Popov et al 2004;Zhou et al 2004;Stewart et al 2005;).…”