scholarly journals Dopamine Receptor Activation Is Required for GABAergic Spike Timing-Dependent Plasticity in Response to Complex Spike Pairing in the Ventral Tegmental Area

2018 ◽  
Vol 10 ◽  
Author(s):  
Ludovic D. Langlois ◽  
Matthieu Dacher ◽  
Fereshteh S. Nugent
Keyword(s):  
Ventral Tegmental Area ◽  
Dopamine Receptor ◽  
Receptor Activation ◽  
Spike Timing ◽  
Spike Timing Dependent Plasticity ◽  
Complex Spike ◽  
Dependent Plasticity ◽  
Ventral Tegmental

scholarly journals Spike timing-dependent plasticity at GABAergic synapses in the ventral tegmental area

2013 ◽  
Vol 591 (19) ◽  
pp. 4699-4710 ◽  
Author(s):  
Jayaraj N. Kodangattil ◽  
Matthieu Dacher ◽  
Michael E. Authement ◽  
Fereshteh S. Nugent
Keyword(s):  
Ventral Tegmental Area ◽  
Spike Timing ◽  
Spike Timing Dependent Plasticity ◽  
Dependent Plasticity ◽  
Gabaergic Synapses ◽  
Ventral Tegmental

Role of AMPA and NMDA Receptors and Back-Propagating Action Potentials in Spike Timing–Dependent Plasticity

2010 ◽  
Vol 103 (1) ◽  
pp. 47-54 ◽  
Author(s):  
Marco Fuenzalida ◽  
David Fernández de Sevilla ◽  
Alejandro Couve ◽  
Washington Buño
Keyword(s):  
Nmda Receptors ◽  
Pyramidal Neurons ◽  
Long Term Potentiation ◽  
Receptor Activation ◽  
Spike Timing ◽  
Spike Timing Dependent Plasticity ◽  
Cellular Mechanisms ◽  
Dependent Plasticity ◽  
Term Potentiation

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.

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

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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