Timing is not everything: neuromodulation opens the STDP gate

Verena Pawlak

doi:10.3389/fnsyn.2010.00146

Abstract

Spike timing dependent plasticity (STDP) is a temporally specific extension of Hebbian associative plasticity that has tied together the timing of presynaptic inputs relative to the postsynaptic single spike. However, it is difficult to translate this mechanism to in vivo conditions where there is an abundance of presynaptic activity constantly impinging upon the dendritic tree as well as ongoing postsynaptic spiking activity that backpropagates along the dendrite. Theoretical studies have proposed that, in addition to this pre- and postsynaptic activity, a “third factor” would enable the association of specific inputs to specific outputs. Experimentally, the picture that is beginning to emerge, is that in addition to the precise timing of pre- and postsynaptic spikes, this third factor involves neuromodulators that have a distinctive influence on STDP rules. Specifically, neuromodulatory systems can influence STDP rules by acting via dopaminergic, noradrenergic, muscarinic, and nicotinic receptors. Neuromodulator actions can enable STDP induction or – by increasing or decreasing the threshold – can change the conditions for plasticity induction. Because some of the neuromodulators are also involved in reward, a link between STDP and reward-mediated learning is emerging. However, many outstanding questions concerning the relationship between neuromodulatory systems and STDP rules remain, that once solved, will help make the crucial link from timing-based synaptic plasticity rules to behaviorally based learning.

Highlights

The first groundbreaking in vitro Spike timing dependent plasticity (STDP) studies seemed to paint a very clear picture: The near-coincidence of presynaptic input and postsynaptic spiking enables neurons to enhance or decrease their synaptic weights depending on the exact timing of these two events (Magee and Johnston, 1997; Markram et al, 1997; Bi and Poo, 1998; Debanne et al, 1998)
The question arises, whether the mere association of presynaptic input and postsynaptic spiking activity would be enough to alter synaptic efficacy, and whether individual synapses in turn continuously scale up and down as inputs and backpropagating spikes constantly interact? do spontaneously occurring spikes (Figure 1C2) and stimulus-evoked spikes (Figure 1C3) change synaptic weights as they interact with presynaptic input (Figure 1D)? When a spike is fired, whether it is spontaneous or evoked, how are active synaptic inputs that are driven by a stimulus separated from those that are due to the ongoing activity? One possible solution to these selectivity problems was originally proposed in relation to reward mediated learning (Miller, 1981; Wickens, 1990)
Acetylcholine via M1 muscarinic Rs; noradrenaline via β-adrenergic Rs timingdependent LTP (t-LTP): 1 excitatory postsynaptic potential (EPSP) timed to 4 action potential (AP); timing-dependent LTD (t-LTD): 4 APs timed to 1 EPSP

Summary

SYNAPTIC NEUROSCIENCE

Edited by: Wulfram Gerstner, Ecole Polytechnique Fédérale de Lausanne, Switzerland. Reviewed by: Markus Diesmann, RIKEN Brain Science Institute, Japan Wulfram Gerstner, Ecole Polytechnique Fédérale de Lausanne, Switzerland Henning Sprekeler , Ecole Polytechnique Fédérale de Lausanne, Switzerland Nicolas Fremaux, Ecole Polytechnique Fédérale de Lausanne, Switzerland Botond Szatmáry , Brain Corporation, USA. The picture that is beginning to emerge, is that in addition to the precise timing of pre- and postsynaptic spikes, this third factor involves neuromodulators that have a distinctive influence on STDP rules. Because some of the neuromodulators are involved in reward, a link between STDP and reward-mediated learning is emerging. Many outstanding questions concerning the relationship between neuromodulatory systems and STDP rules remain, that once solved, will help make the crucial link from timing-based synaptic plasticity rules to behaviorally based learning

Introduction

Neuromodulation and STDP

Spiny projection neurons

Application of agonists

Conclusion