Modulation of Spike-Timing Dependent Plasticity: Towards the Inclusion of a Third Factor in Computational Models

• Published in: Frontiers in computational neuroscience Vol. 12; p. 49
• Main Authors: Foncelle, Alexandre, Mendes, Alexandre, Jędrzejewska-Szmek, Joanna, Valtcheva, Silvana, Berry, Hugues, Blackwell, Kim T, Venance, Laurent
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Research Foundation 03.07.2018; Frontiers; Frontiers Media S.A
• Subjects: Acetylcholine; Astrocytes; Brain-derived neurotrophic factor; Calcium signalling; Computational neuroscience; Dopamine; Dopamine receptors; Firing pattern; Glutamic acid receptors (ionotropic); Life Sciences; N-Methyl-D-aspartic acid receptors; Neuromodulation; Neuronal-glial interactions; Neurons; Neurons and Cognition; Neuroscience; Nitric oxide; noradrenaline; Norepinephrine; Quantitative Methods; Receptor mechanisms; Signal transduction; STDP; Synaptic plasticity; Synaptic strength; third factor; γ-Aminobutyric acid; France; Hebbian plasticity; eligibility traces; third factor; noradrenaline; STDP; acetylcholine; astrocytes; dopamine; NO; M X; GABA Modulators; muscarinic acetylcholine receptors; input-timing dependent plasticity; mGluR; nAChRs; Third factor; ITDP; timing-dependent long term potentiation; Noradrenaline; tLTP; Spike-timing dependent plasticity (STDP); nitric oxide; Dopamine; Astrocytes; BDNF; metabotropic glutamatergic receptor; muscarinic type-X receptor; Credit assignment; gamma-aminobutyric acid; Computational model; extracellular signal–regulated kinase; spike-timing dependent plasticity; mAChRs; Eligibility Traces; N-methyl-D-aspartate receptor; GABA; NMDAR; Acetylcholine; nicotinic acetylcholine receptors; tLTD; timing-dependent long term depression; ERK
• ISSN: 1662-5188; 1662-5188
• DOI: 10.3389/fncom.2018.00049

In spike-timing dependent plasticity (STDP) change in synaptic strength depends on the timing of pre- vs. postsynaptic spiking activity. Since STDP is in compliance with Hebb's postulate, it is considered one of the major mechanisms of memory storage and recall. STDP comprises a system of two coincidence detectors with N-methyl-D-aspartate receptor (NMDAR) activation often posited as one of the main components. Numerous studies have unveiled a third component of this coincidence detection system, namely neuromodulation and glia activity shaping STDP. Even though dopaminergic control of STDP has most often been reported, acetylcholine, noradrenaline, nitric oxide (NO), brain-derived neurotrophic factor (BDNF) or gamma-aminobutyric acid (GABA) also has been shown to effectively modulate STDP. Furthermore, it has been demonstrated that astrocytes, via the release or uptake of glutamate, gate STDP expression. At the most fundamental level, the timing properties of STDP are expected to depend on the spatiotemporal dynamics of the underlying signaling pathways. However in most cases, due to technical limitations experiments grant only indirect access to these pathways. Computational models carefully constrained by experiments, allow for a better qualitative understanding of the molecular basis of STDP and its regulation by neuromodulators. Recently, computational models of calcium dynamics and signaling pathway molecules have started to explore STDP emergence in and -like conditions. These models are expected to reproduce better at least part of the complex modulation of STDP as an emergent property of the underlying molecular pathways. Elucidation of the mechanisms underlying STDP modulation and its consequences on network dynamics is of critical importance and will allow better understanding of the major mechanisms of memory storage and recall both in health and disease.