Glutamatergic synapses are structurally and biochemically complex because of multiple plasticity processes: long-term potentiation, long-term depression, short-term potentiation and scaling

Abstract

Synapses are complex because they perform multiple functions, including at least six mechanistically different forms of plasticity. Here, I comment on recent developments regarding these processes. (i) Short-term potentiation (STP), a Hebbian processthat requires small amounts of synaptic input, appearsto make strong contributions to some forms of working memory. (ii) The rules for long-term potentiation (LTP) induction in CA3 have been clarified: induction does not depend obligatorily on backpropagating sodium spikes but, rather, on dendritic branch-specific N-methyl-D-aspartate (NMDA) spikes. (iii) Late LTP, a process that requires a dopamine signal (and is therefore neoHebbian), is mediated by trans-synaptic growth of the synapse, a growth that occurs about an hour after LTP induction. (iv) LTD processes are complex and include both homosynaptic and heterosynaptic forms. (v) Synaptic scaling produced by changes in activity levels are not primarily cell-autonomous, but rather depend on network activity. (vi) The evidence for distance-dependent scaling along the primary dendrite is firm, and a plausible structural-based mechanism is suggested.Ideas about the mechanisms of synaptic function need to take into consideration newly emerging data about synaptic structure. Recent superresolution studies indicate that glutamatergic synapses are modular (module size 70 -80 nm), as predicted by theoretical work. Modules are trans-synaptic structures and have high concentrations of postsynaptic density-95 (PSD-95) and a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor. These modules function as quasi-independent loci of AMPA-mediated transmission and may be independently modifiable, suggesting a new understanding of quantal transmission.This article is part of the themed issue 'Integrating Hebbian and homeostatic plasticity.'

Integrating Hebbian and homeostatic plasticity: the current state of the field and future research directions

“…A simulation study of recurrently connected networks suggests that such fluctuations can stabilize network activity by constitutively restoring the spine size distribution close to the physiological steady-state distribution, while ongoing Hebbian plasticity forms and maintains cell assemblies [44,45]. In addition to changes in the structural size of synapses, the properties and activation of NMDA receptors within a synapse have been implicated in monitoring overall changes to activity levels [46].…”

“…Numerous homeostatic plasticity mechanisms (synaptic scaling, changes to the balance between excitation and inhibition, changes in excitability, spine size fluctuations; [99]) and Hebbian mechanisms (short-term plasticity, shortterm potentiation, LTP, LTD [46]) have been described. These mechanisms have largely been studied in isolation and there is limited understanding of how these mechanisms may interact.…”

Integrating Hebbian and homeostatic plasticity: introduction

“…The paper by Lisman [2] lays the groundwork for what we understand about Hebbian plasticity. The paper by Turrigiano [3] sets out the nature of homeostatic plasticity and synaptic scaling as well as reminiscing on the difficult birth of the first paper on this topic!…”

“…The Lisman position paper makes clear at the start the scope of the problem with which scientists are faced in understanding plasticity; it is argued that the synapse supports six types of plasticity, three of which might be described as Hebbian (short-term potentiation (STP), LTP and long-term depression (LTD)) and two homeostatic (synaptic scaling-and distance-dependent scaling). The other form of plasticity is late phase LTP, which, it is argued, is not strictly Hebbian [2] and concerns structural changes at the synapse. The Turrigiano position paper explains the requirement for a homeostatic plasticity mechanism that continually tunes the synapses in the neuronal circuit to maintain neurons at their firing rate set points.…”

Exercise during abstinence normalizes ultrastructural synaptic plasticity associated with nicotine‐seeking following extended access self‐administration

“…These types of changes are thought to occur through a Hebbian form of long‐term potentiation (LTP) and happen within seconds or minutes following activity‐dependent neuronal activation (Fauth & Tetzlaff, ). However, some of the changes observed here, particularly the elongation of synapses, were likely mediated by nicotine self‐administration and abstinence given that we obtained the tissue immediately after the test session and these changes require several hours or days to occur (Lisman, ). The elongation of synapses is likely slower because the processes needed for the integration of additional AMPARs, namely the growth of presynaptic boutons, the enlargement of the PSD, and protein synthesis (Lisman, ), take time.…”