Food Restriction Increases Glutamate Receptor-Mediated Burst Firing of Dopamine Neurons

Fasting and food restriction alter the activity of the mesolimbic dopamine system to affect multiple reward-related behaviors. Food restriction decreases baseline dopamine levels in efferent target sites and enhances dopamine release in response to rewards such as food and drugs. In addition to releasing dopamine from axon terminals, dopamine neurons in the ventral tegmental area (VTA) also release dopamine from their soma and dendrites, and this somatodendritic dopamine release acts as an autoinhibitory signal to inhibit neighboring VTA dopamine neurons. It is unknown whether acute fasting also affects dopamine release, including the local inhibitory somatodendritic dopamine release in the VTA. In these studies, I have tested whether fasting affects the inhibitory somatodendritic dopamine release within the VTA by examining whether an acute 24-h fast affects the inhibitory postsynaptic current mediated by evoked somatodendritic dopamine release (D2R IPSC). Fasting increased the contribution of the first action potential to the overall D2R IPSC and increased the ratio of repeated D2R IPSCs evoked at short intervals. Fasting also reduced the effect of forskolin on the D2R IPSC and led to a significantly bigger decrease in the D2R IPSC in low extracellular calcium. Finally, fasting resulted in an increase in the D2R IPSCs when a more physiologically relevant train of D2R IPSCs was used. Taken together, these results indicate that fasting caused a change in the properties of somatodendritic dopamine release, possibly by increasing dopamine release, and that this increased release can be sustained under conditions where dopamine neurons are highly active.

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Iontophoretically administered drugs acting at the N-methyl-D-aspartate receptor modulate burst firing in A9 dopamine neurons in the rat

Synapse ◽

10.1002/syn.890100208 ◽

1992 ◽

Vol 10 (2) ◽

pp. 131-140 ◽

Cited By ~ 156

Author(s):

Paul Overton ◽

David Clark

Keyword(s):

Burst Firing ◽

Dopamine Neurons ◽

Aspartate Receptor

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Dopamine, behavior, and addiction

Journal of Biomedical Science ◽

10.1186/s12929-021-00779-7 ◽

2021 ◽

Vol 28 (1) ◽

Author(s):

Roy A. Wise ◽

Chloe J. Jordan

Keyword(s):

Dopaminergic Neurons ◽

Long Term Potentiation ◽

Burst Firing ◽

Dopamine Neurons ◽

Dopamine System ◽

Learned Behavior ◽

Sensory Inputs ◽

Addictive Drugs ◽

Term Potentiation

AbstractAddictive drugs are habit-forming. Addiction is a learned behavior; repeated exposure to addictive drugs can stamp in learning. Dopamine-depleted or dopamine-deleted animals have only unlearned reflexes; they lack learned seeking and learned avoidance. Burst-firing of dopamine neurons enables learning—long-term potentiation (LTP)—of search and avoidance responses. It sets the stage for learning that occurs between glutamatergic sensory inputs and GABAergic motor-related outputs of the striatum; this learning establishes the ability to search and avoid. Independent of burst-firing, the rate of single-spiking—or “pacemaker firing”—of dopaminergic neurons mediates motivational arousal. Motivational arousal increases during need states and its level determines the responsiveness of the animal to established predictive stimuli. Addictive drugs, while usually not serving as an external stimulus, have varying abilities to activate the dopamine system; the comparative abilities of different addictive drugs to facilitate LTP is something that might be studied in the future.

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Mechanisms for multiple activity modes of VTA dopamine neurons

10.1101/008920 ◽

2014 ◽

Author(s):

Andrew M. Oster ◽

Philippe Faure ◽

Boris S. Gutkin

Keyword(s):

Cell Activity ◽

Burst Firing ◽

Dopamine Neurons ◽

Substantia Nigra Pars Compacta ◽

Depolarization Block ◽

Gaba Inhibition ◽

Potassium Dynamics ◽

Firing Mode ◽

Sudden Decrease

Midbrain ventral segmental area (VTA) dopaminergic neurons send numerous projections to cortical and sub-cortical areas, and diffusely release dopamine (DA) to their targets. DA neurons display a range of activity modes that vary in frequency and degree of burst ring. Importantly, DA neuronal bursting is associated with a significantly greater degree of DA release than an equivalent tonic activity pattern. Here, we introduce a single compartmental, conductance-based computational model for DA cell activity that captures the behavior of DA neuronal dynamics and examine the multiple factors that underlie DA firing modes: the strength of the SK conductance, the amount of drive, and GABA inhibition. Our results suggest that neurons with low SK conductance are in a fast firing mode, are correlated with burst firing, and require higher levels of applied current before undergoing depolarization block. We go on to consider the role of GABAergic inhibition on an ensemble of dynamical classes of DA neurons and find that strong GABA inhibition suppresses burst firing. Our studies suggest differences in the distribution of the SK conductance and GABA inhibition levels may indicate subclasses of DA neurons within the VTA. We further identify, that by considering alternate potassium dynamics, the dynamics display burst patterns that terminate via depolarization block, akin to those observed in vivo in VTA DA neurons and in substantia nigra pars compacta DA cell preparations under apamin application. In addition, we consider the generation of transient burst ring events that are NMDA-initiated or elicited by a sudden decrease of GABA inhibition, that is, disinhibition.

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A Modeling Study Suggests Complementary Roles for GABAA and NMDA Receptors and the SK Channel in Regulating the Firing Pattern in Midbrain Dopamine Neurons

Journal of Neurophysiology ◽

10.1152/jn.00062.2003 ◽

2004 ◽

Vol 91 (1) ◽

pp. 346-357 ◽

Cited By ~ 57

Author(s):

Alexander O. Komendantov ◽

Olena G. Komendantova ◽

Steven W. Johnson ◽

Carmen C. Canavier

Keyword(s):

Experimental Data ◽

Firing Pattern ◽

Receptor Activation ◽

Burst Firing ◽

Dopamine Neurons ◽

Sk Channels ◽

Sk Channel ◽

The Difference

Midbrain dopaminergic (DA) neurons in vivo exhibit two major firing patterns: single-spike firing and burst firing. The firing pattern expressed is dependent on both the intrinsic properties of the neurons and their excitatory and inhibitory synaptic inputs. Experimental data suggest that the activation of N-methyl-d-aspartate (NMDA) and GABAA receptors is a crucial contributor to the initiation and suppression of burst firing, respectively, and that blocking Ca2+-activated potassium SK channels can facilitate burst firing. A multi-compartmental model of a DA neuron with a branching structure was developed and calibrated based on in vitro experimental data to explore the effects of different levels of activation of NMDA and GABAA receptors as well as the modulation of the SK current on the firing activity. The simulated tonic activation of GABAA receptors was calibrated by taking into account the difference in the electrotonic properties in vivo versus in vitro. Although NMDA-evoked currents are required for burst generation in the model, currents evoked by GABAA-receptor activation can also regulate the firing pattern. For example, the model predicts that increasing the level of NMDA receptor activation can produce excessive depolarization that prevents burst firing, but a concurrent increase in the activation of GABAA receptors can restore burst firing. Another prediction of the model is that blocking the SK channel current in vivo will facilitate bursting, but not as robustly as blocking the GABAA receptors.

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