NMDA receptors in axons: there's no coincidence

Abstract

conducted his PhD research in Prof. Christine Holt's lab at the University of Cambridge, where he revealed how RNA trafficking and highly localized protein synthesis in axons regulate synaptogenesis in vivo. For his HBHL and FRQS Postdoctoral Fellowships, he joined Prof. Jesper Sjöström's lab to pursue his keen interest in presynaptic plasticity in neurotransmission. P. Jesper Sjöström is Associate Professor in Neuroscience at McGill University's Centre for Research in Neuroscience and holds an FRQS Chercheur-Boursier Senior award. His team explores plasticity in the brain using quadruple patch-clamp, two-photon microscopy, optogenetics and computer modelling. His research has unveiled plasticity learning rules, neocortical connectivity patterns and unconventional forms of NMDA receptor signalling. He

Presynaptic NMDA receptors facilitate short-term plasticity and BDNF release at hippocampal mossy fiber synapses

“…In addition to facilitating evoked neurotransmitter release, preNMDARs can promote spontaneous neurotransmitter release as indicated by changes in miniature, action potential-independent activity (e.g. mEPSCs) (for recent reviews, see Banerjee et al, 2016; Kunz, Roberts, & Philpot, 2013; Wong et al, 2020). A potential role for preNMDARs in spontaneous, action potential-independent release at mossy fiber synapses cannot be discarded.…”

“…Given the multiple signaling cascades known to regulate NMDARs (Lau & Zukin, 2007; Sanz-Clemente, Nicoll, & Roche, 2013), preNMDARs at mossy fiber synapses may provide an important site of neuromodulatory control. PreNMDARs have been implicated in the induction of LTP and LTD at excitatory or inhibitory synapses in several brain areas (Banerjee et al, 2016; Wong et al, 2020). While most evidence, at least using robust induction protocols in vitro , indicates that long-term forms of presynaptic plasticity at mossy fiber synapses can occur in the absence of NMDAR activation (Castillo, 2012; Nicoll & Schmitz, 2005), our findings do not discard the possibility that preNMDARs could play a role in vivo during subtle presynaptic activities.…”

“…Chen, Chen, Chen, Zhang, & Pan, 2019; Zeng, Thomson, Aicher, & Terman, 2006), and epilepsy (Yang, Woodhall, & Jones, 2006). At present, however, in vivo evidence for the involvement of preNMDARs in brain function and disease is rather indirect (Bouvier et al, 2015; Wong et al, 2020). The development of specific preNMDAR tools is required to determine the functional impact of these receptors in vivo .…”

“…There is evidence that preNMDARs can operate as coincidence detectors at some synapses (Duguid, 2013; Wong et al, 2020). At the mf-CA3 synapse, we found that preNMDARs contribute to LFF (i.e.…”

“…The activation of ionotropic and metabotropic presynaptic receptors provides a powerful way of fine tuning neurotransmission via the facilitation or inhibition of neurotransmitter release (Burke & Bender, 2019; Engelman & MacDermott, 2004; Miller, 1998; Pinheiro & Mulle, 2008; Schicker, Dorostkar, & Boehm, 2008). Due to their unique functional properties, including high calcium-permeability, slow kinetics and well-characterized role as coincidence-detectors (Cull-Candy, Brickley, & Farrant, 2001; Lau & Zukin, 2007; Paoletti, Bellone, & Zhou, 2013; Traynelis et al, 2010), presynaptic NMDA receptors (preNMDARs) have emerged as key regulators of synaptic transmission and plasticity (Banerjee, Larsen, Philpot, & Paulsen, 2016; Bouvier, Bidoret, Casado, & Paoletti, 2015; Bouvier, Larsen, Rodriguez-Moreno, Paulsen, & Sjostrom, 2018; Duguid, 2013; Duguid & Smart, 2009; Wong, Rannio, Jones, Thomazeau, & Sjostrom, 2020). Regulation of neurotransmitter release by NMDA autoreceptors in the brain was suggested three decades ago (Martin, Bustos, Bowe, Bray, & Nadler, 1991).…”