ReviewAMPA receptor regulation during synaptic plasticity in hippocampus and neocortex
Highlights
► Many forms of synaptic plasticity depend on AMPAR regulation. ► Different forms of synaptic plasticity often tap into similar mechanisms of AMPAR regulation. ► Synaptic plasticity in hippocampus and neocortex share similarities, but also show differences. ► In particular, they display some differences in regulation of Ca2+-permeable AMPARs. ► The differences may reflect distinct functional requirement of these brain areas.
Introduction
Rapid activity-dependent mechanisms of synaptic plasticity, such as LTP and LTD, are believed to be central for the proper development of brain connectivity and for the coding and storage of memory. Because both LTP and LTD have innate built-in positive-feedback propensity, there is a requirement for global homeostatic plasticity mechanisms acting on a slower time scale to provide stability to the overall neuronal activity [1], [2]. Most of our understanding on synaptic plasticity mechanisms derives from hippocampal studies, in part because this structure is critical for memory formation, but also because synaptic plasticity is particularly robust in this area. Although multiple forms of LTP and LTD are expressed in the hippocampus, even at the same synapses [3], the most commonly studied form of LTP/LTD is NMDAR receptor (NMDAR)-dependent, and is predominantly studied at the Schaffer collateral to CA1 synapses. The mechanisms of LTP and LTD induced at the CA1 synapses are known to an extensive molecular detail, which mainly involve regulation of AMPARs [4], [5] (see Section 2.3). While many of the basic mechanisms of AMPAR regulation during synaptic plasticity in the hippocampus apply to synapses else where, there are critical differences, which underscores the specific functional requirement of the synapses under study.
Hippocampus is part of the archicortex, which is structurally different from the 6-layered neocortex. Despite the anatomical and functional distinctions, synapses in both brain areas display common forms of synaptic plasticity. Early studies done by Mark Bear's group reported that the bidirectional regulation of synapses in layer 2/3 of visual cortex shares common induction mechanisms with synapses in the CA1, including the dependence on NMDARs [6]. Later studies uncovered further commonalities, including mechanisms of AMPAR regulation, but also revealed important differences in the induction mechanisms of LTP and LTD across neocortical layers [7], [8]. However, for the purpose of meaningful comparisons we will limit our discussions to the NMDAR-dependent forms of LTP/LTD in layer 2/3 of the neocortex and the Schaffer collateral to CA1 synapses. NMDAR-dependent LTP and LTD are expressed postsynaptically via regulation of AMPARs, which are also utilized by global homeostatic synaptic plasticity. Therefore we will compare AMPAR regulation during LTP/LTD and homeostatic synaptic plasticity in these two brain areas.
Section snippets
LTP/LTD in CA1 and neocortex
Kirkwood et al. first convincingly demonstrated that common forms of NMDAR-dependent of LTP and LTD are present at the Schaffer collateral synapses in the hippocampal CA1 and the layer 4 to 2/3 synapses in the visual cortex [6]. At both types of synapses, theta burst stimulation induces LTP and low frequency stimulation (1-Hz, 900 pulses) produces LTD. Also in both areas, the induction of LTP is Hebbian, requiring co-incident pre- and post-synaptic activity [9], which is a property conferred by
Conclusions
Hippocampal synapses, especially the Schaffer collateral inputs to CA1, have been instrumental in unraveling many of the fundamental mechanisms of synaptic plasticity. While many of the basic mechanisms are conserved across brain areas, there are specific differences. Recent studies highlight that the neocortex has a distinct functional role in that it contributes to the long-term storage of memories, and in particular sensory cortices need to respond to changes in sensory demand that is tied
Acknowledgement
This work was supported by NIH grants to H.-K.L. (R01-EY014882) and A.K. (R01-EY12124).
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