Dopamine Receptor Activation Is Required for Corticostriatal Spike-Timing-Dependent Plasticity

The cellular mechanisms that mediate spike timing–dependent plasticity (STDP) are largely unknown. We studied in vitro in CA1 pyramidal neurons the contribution of AMPA and N-methyl-d-aspartate (NMDA) components of Schaffer collateral (SC) excitatory postsynaptic potentials (EPSPs; EPSPAMPA and EPSPNMDA) and of the back-propagating action potential (BAP) to the long-term potentiation (LTP) induced by a STDP protocol that consisted in pairing an EPSP and a BAP. Transient blockade of EPSPAMPA with 7-nitro-2,3-dioxo-1,4-dihydroquinoxaline-6-carbonitrile (CNQX) during the STDP protocol prevented LTP. Contrastingly LTP was induced under transient inhibition of EPSPAMPA by combining SC stimulation, an imposed EPSPAMPA-like depolarization, and BAP or by coupling the EPSPNMDA evoked under sustained depolarization (approximately −40 mV) and BAP. In Mg2+-free solution EPSPNMDA and BAP also produced LTP. Suppression of EPSPNMDA or BAP always prevented LTP. Thus activation of NMDA receptors and BAPs are needed but not sufficient because AMPA receptor activation is also obligatory for STDP. However, a transient depolarization of another origin that unblocks NMDA receptors and a BAP may also trigger LTP.

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An ultra-low frequency spike timing dependent plasticity-based approach for treating alcohol use disorder

10.1101/2021.09.16.460673 ◽

2021 ◽

Author(s):

Anders J Asp ◽

Suelen Lucio Boschen ◽

J Luis Lujan

Keyword(s):

Alcohol Consumption ◽

Alcohol Use ◽

Dopamine Receptor ◽

Alcohol Use Disorder ◽

Spike Timing ◽

Synaptic Function ◽

Chronic Alcohol ◽

Spike Timing Dependent Plasticity ◽

Chronic Alcohol Consumption ◽

Dependent Plasticity

Alcohol use disorder (AUD) is a chronic relapsing brain disorder characterized by an impaired ability to stop or control alcohol consumption despite adverse social, occupational, or health consequences. AUD affects nearly one-third of adults at some point during their lives, with an associated cost of approximately $249 billion annually in the U.S. alone. The effects of alcohol consumption are expected to increase significantly during the COVID-19 pandemic, with alcohol sales increased by approximately 54%, potentially exacerbating health concerns and risk-taking behaviors. Unfortunately, existing pharmacological and behavioral therapies for AUD have historically been associated with poor success rates, with approximately 40% of individuals relapsing within three years of treatment. Pre-clinical studies have shown that chronic alcohol consumption leads to significant changes in synaptic function within the dorsal medial striatum (DMS), one of the brain regions associated with AUD and responsible for mediating goal-directed behavior. Specifically, chronic alcohol consumption has been associated with hyperactivity of dopamine receptor 1 (D1) medium spiny neurons (MSN) and hypoactivity of dopamine receptor 2 (D1) MSNs within the DMS. Optogenetic, chemogenetic, and transgenic approaches have demonstrated that reducing the D1/D2 MSN signaling imbalance decreases alcohol self-administration in rodent models of AUD. However, these approaches cannot be studied clinically at this time. Here, we present an electrical stimulation alternative that uses ultra-low (<=1Hz) frequency (ULF) spike-timing dependent plasticity (STDP) to reduce DMS D1/D2 MSN signaling imbalances by stimulating D1-MSN afferents into the GPi and ACC glutamatergic projections to the DMS in a time-locked stimulation sequence. Our data suggest that GPi/ACC ULF-STDP selectively decreases DMS D1-MSN hyperactivity leading to reduced alcohol consumption without evoking undesired affective behaviors in a two-bottle choice mouse model of AUD.

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Spike timing-dependent plasticity in sparse recurrent neural networks

IEICE Proceeding Series ◽

10.15248/proc.1.485 ◽

2014 ◽

Vol 1 ◽

pp. 485-488

Author(s):

Hideyuki Kato ◽

Tohru Ikeguchi

Keyword(s):

Neural Networks ◽

Recurrent Neural Networks ◽

Spike Timing ◽

Spike Timing Dependent Plasticity ◽

Dependent Plasticity

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Faculty Opinions recommendation of Postsynaptic depolarization requirements for LTP and LTD: a critique of spike timing-dependent plasticity.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1028219.335094 ◽

2005 ◽

Author(s):

Dan Johnston

Keyword(s):

Spike Timing ◽

Spike Timing Dependent Plasticity ◽

Dependent Plasticity

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Stable Competitive Dynamics Emerge from Multispike Interactions in a Stochastic Model of Spike-Timing-Dependent Plasticity

Neural Computation ◽

10.1162/neco.2006.18.10.2414 ◽

2006 ◽

Vol 18 (10) ◽

pp. 2414-2464 ◽

Cited By ~ 19

Author(s):

Peter A. Appleby ◽

Terry Elliott

Keyword(s):

Synaptic Plasticity ◽

Stochastic Model ◽

Higher Order ◽

Spike Timing ◽

Competitive Dynamics ◽

Spike Timing Dependent Plasticity ◽

Interaction Function ◽

Dependent Plasticity ◽

Order Interaction ◽

Synaptic Dynamics

In earlier work we presented a stochastic model of spike-timing-dependent plasticity (STDP) in which STDP emerges only at the level of temporal or spatial synaptic ensembles. We derived the two-spike interaction function from this model and showed that it exhibits an STDP-like form. Here, we extend this work by examining the general n-spike interaction functions that may be derived from the model. A comparison between the two-spike interaction function and the higher-order interaction functions reveals profound differences. In particular, we show that the two-spike interaction function cannot support stable, competitive synaptic plasticity, such as that seen during neuronal development, without including modifications designed specifically to stabilize its behavior. In contrast, we show that all the higher-order interaction functions exhibit a fixed-point structure consistent with the presence of competitive synaptic dynamics. This difference originates in the unification of our proposed “switch” mechanism for synaptic plasticity, coupling synaptic depression and synaptic potentiation processes together. While three or more spikes are required to probe this coupling, two spikes can never do so. We conclude that this coupling is critical to the presence of competitive dynamics and that multispike interactions are therefore vital to understanding synaptic competition.

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