scholarly journals Dopamine in the basal amygdala signals salient somatosensory events during fear learning

2019 ◽  
Author(s):  
Wei Tang ◽  
Olexiy Kochubey ◽  
Michael Kintscher ◽  
Ralf Schneggenburger
Keyword(s):  
Memory Retrieval ◽  
Dopamine Release ◽  
Brain Area ◽  
Dopamine Neurons ◽  
Fear Learning ◽  
Dopamine Concentration ◽  
Axon Terminals ◽  
Basal Amygdala ◽  
Teaching Signal

SummaryThe amygdala is a brain area critical for the formation of threat memories. However, the nature of the teaching signal(s) that drive plasticity in the amygdala are still under debate. Here, we use optogenetic methods to investigate whether dopamine release in the amygdala contributes to fear learning. Antero- and retrograde labeling showed that a sparse, and relatively evenly distributed population of ventral tegmental area (VTA) neurons projects to the basal amygdala (BA). In-vivo optrode recordings in behaving mice showed that many VTA neurons, amongst them putative dopamine neurons, are excited by footshocks. Correspondingly, in-vivo fiber photometry of dopamine in the BA revealed robust dopamine concentration transients upon footshock presentation. Finally, silencing VTA dopamine neurons, or their axon terminals in the BA during the footshock, reduced the extent of threat memory retrieval one day later. Thus, VTA dopamine neurons projecting to the BA code for the saliency of the footshock event, and the resulting dopamine release in the BA facilitates threat memory formation.

scholarly journals Acute fasting increases somatodendritic dopamine release in the ventral tegmental area

2015 ◽  
Vol 114 (2) ◽  
pp. 1072-1082 ◽  
Author(s):  
Aaron G. Roseberry
Keyword(s):  
Ventral Tegmental Area ◽  
Food Restriction ◽  
Dopamine Release ◽  
Dopamine Neurons ◽  
Dopamine System ◽  
Mesolimbic Dopamine System ◽  
Axon Terminals ◽  
Highly Active ◽  
Target Sites ◽  
Ventral Tegmental

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.

scholarly journals Cell-intrinsic effects of TorsinA(ΔE) disrupt dopamine release in a mouse model of DYT1-TOR1A dystonia

2020 ◽  
Author(s):  
Anthony M. Downs ◽  
Xueliang Fan ◽  
Radhika Kadakia ◽  
Yuping Donsante ◽  
H.A. Jinnah ◽  
...  
Keyword(s):  
Dopamine Release ◽  
Ex Vivo ◽  
Dopamine Neurons ◽  
Striatal Dopamine ◽  
Cholinergic Interneurons ◽  
Base Pair Deletion ◽  
Presynaptic Mechanisms ◽  
Conditional Expression ◽  
Striatal Dopamine Release

ABSTRACTDYT1-TOR1A dystonia is an inherited dystonia caused by a three base-pair deletion in the TOR1A gene (TOR1AΔE). Although the mechanisms underlying the dystonic movements are largely unknown, abnormalities in striatal dopamine and acetylcholine neurotransmission are consistently implicated whereby dopamine release is reduced while cholinergic tone is increased. Because striatal cholinergic neurotransmission mediates dopamine release, it is not known if the dopamine release deficit is mediated indirectly by abnormal acetylcholine neurotransmission or if Tor1a(ΔE) acts directly within dopaminergic neurons to attenuate release. To dissect the microcircuit that governs the deficit in dopamine release, we conditionally expressed Tor1a(ΔE) in either dopamine neurons or cholinergic interneurons in mice and assessed striatal dopamine release using ex vivo fast scan cyclic voltammetry or dopamine efflux using in vivo microdialysis. Conditional expression of Tor1a(ΔE) in cholinergic neurons did not affect striatal dopamine release. In contrast, conditional expression of Tor1a(ΔE) in dopamine neurons reduced dopamine release to 50% of normal, which is comparable to the deficit in Tor1a+/ΔE knockin mice that express the mutation ubiquitously. Despite the deficit in dopamine release, we found that the Tor1a(ΔE) mutation does not cause obvious nerve terminal dysfunction as other presynaptic mechanisms, including electrical excitability, vesicle recycling/refilling, Ca2+ signaling, D2 dopamine autoreceptor function and GABAB receptor function, are intact. Although the mechanistic link between Tor1a(ΔE) and dopamine release is unclear, these results clearly demonstrate that the defect in dopamine release is caused by the action of the Tor1a(ΔE) mutation within dopamine neurons.

scholarly journals A transient dopamine signal encodes subjective value and causally influences demand in an economic context

2017 ◽  
Vol 114 (52) ◽  
pp. E11303-E11312 ◽  
Author(s):  
Scott A. Schelp ◽  
Katherine J. Pultorak ◽  
Dylan R. Rakowski ◽  
Devan M. Gomez ◽  
Gregory Krzystyniak ◽  
...  
Keyword(s):  
Prediction Error ◽  
Dopamine Release ◽  
Dopamine Neurons ◽  
Price Sensitivity ◽  
Mesolimbic Dopamine ◽  
Fast Scan Cyclic Voltammetry ◽  
Reward Prediction Error ◽  
Dopamine Concentration ◽  
Reward Prediction ◽  
Subjective Value

The mesolimbic dopamine system is strongly implicated in motivational processes. Currently accepted theories suggest that transient mesolimbic dopamine release events energize reward seeking and encode reward value. During the pursuit of reward, critical associations are formed between the reward and cues that predict its availability. Conditioned by these experiences, dopamine neurons begin to fire upon the earliest presentation of a cue, and again at the receipt of reward. The resulting dopamine concentration scales proportionally to the value of the reward. In this study, we used a behavioral economics approach to quantify how transient dopamine release events scale with price and causally alter price sensitivity. We presented sucrose to rats across a range of prices and modeled the resulting demand curves to estimate price sensitivity. Using fast-scan cyclic voltammetry, we determined that the concentration of accumbal dopamine time-locked to cue presentation decreased with price. These data confirm and extend the notion that dopamine release events originating in the ventral tegmental area encode subjective value. Using optogenetics to augment dopamine concentration, we found that enhancing dopamine release at cue made demand more sensitive to price and decreased dopamine concentration at reward delivery. From these observations, we infer that value is decreased because of a negative reward prediction error (i.e., the animal receives less than expected). Conversely, enhancing dopamine at reward made demand less sensitive to price. We attribute this finding to a positive reward prediction error, whereby the animal perceives they received a better value than anticipated.

scholarly journals Glial Cell Line–Derived Neurotrophic Factor Receptor Rearranged During Transfection Agonist Supports Dopamine Neurons In Vitro and Enhances Dopamine Release In Vivo

2019 ◽  
Vol 35 (2) ◽  
pp. 245-255 ◽  
Author(s):  
Arun Kumar Mahato ◽  
Jaakko Kopra ◽  
Juho‐Matti Renko ◽  
Tanel Visnapuu ◽  
Ilari Korhonen ◽  
...  
Keyword(s):  
Cell Line ◽  
Glial Cell ◽  
Neurotrophic Factor ◽  
Dopamine Release ◽  
Dopamine Neurons

scholarly journals Dopamine-dependent cAMP dynamics in basal amygdala glutamatergic neurons

2021 ◽  
Author(s):  
Andrew Lutas ◽  
Kayla Fernando ◽  
Stephen X Zhang ◽  
Abhijeet Sambangi ◽  
Mark L Andermann
Keyword(s):  
Dopamine Release ◽  
Receptor Activation ◽  
Downstream Signaling ◽  
Negative Valence ◽  
Glutamatergic Neurons ◽  
Basal Amygdala ◽  
Motivational Salience ◽  
Almost All

Dopaminergic inputs to basal amygdala (BA) instruct learning of motivational salience. Here, we investigated the dynamics of dopamine release and downstream signaling during multiple salient events occurring within tens of seconds. We established in vitro and in vivo real-time tracking and manipulation of cAMP - a key intracellular plasticity signal downstream of dopamine receptor activation. Optogenetically-evoked release of dopamine drove proportional increases in cAMP in almost all BA glutamatergic neurons, suggesting widespread actions of dopamine across neurons preferring positive or negative valence. These cAMP responses decayed more slowly than dopamine release, potentially extending the window of plasticity. cAMP levels accumulated following direct photostimulation of cAMP but not repeated stimulation of dopamine axons, due to potent depression of dopamine release. cAMP and protein kinase A (PKA) responses to repeated appetitive or aversive stimuli also exhibited pronounced depression. Thus, history-dependent dynamics of dopamine and cAMP may regulate learning of temporally clustered, salient stimuli.

scholarly journals Synaptotagmin-7 enhances phasic dopamine release

2021 ◽  
Author(s):  
Skyler L Jackman ◽  
Sarah A Kissiwaa ◽  
Joseph J Lebowitz ◽  
Kim A Engeln ◽  
Anna M Bowman ◽  
...  
Keyword(s):  
Calcium Binding ◽  
Dopamine Release ◽  
Low Frequency ◽  
Dopamine Neurons ◽  
Substantia Nigra Pars Compacta ◽  
Short Term ◽  
Low Frequency Stimulation ◽  
Frequency Stimulation ◽  
Dopamine Signaling

Dopamine released from substantia nigra pars compacta (SNc) neurons modulates movement, motivation, and reward. In addition to their tonic firing pattern, dopamine neurons also fire high-frequency bursts that cause superlinear increases in dopamine release. To examine this poorly understood form of short-term plasticity, we used the fluorescent dopamine sensor dLight1.3b to examine the role of the calcium-binding protein synaptotagmin-7 (SYT7). We report that SYT7 mediates a hidden component of facilitation, which was unmasked by lowering initial release probability, or by low-frequency stimulation of nerve terminals. In Syt7 KO neurons, there was profound synaptic depression that significantly reduced release during stimulations that mimic in vivo firing patterns of SNc neurons. D2-mediated inhibitory postsynaptic currents in the SNc revealed a similar role for SYT7 in somatodendritic release. Our results indicate that SYT7 drives short-term facilitation of release from dopamine neurons, which likely underlies frequency-dependence of dopamine signaling in vivo.

scholarly journals A descending dopamine pathway conserved from basal vertebrates to mammals

2016 ◽  
Vol 113 (17) ◽  
pp. E2440-E2449 ◽  
Author(s):  
Dimitri Ryczko ◽  
Jackson J. Cone ◽  
Michael H. Alpert ◽  
Laurent Goetz ◽  
François Auclair ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Basal Ganglia ◽  
Dopamine Release ◽  
Pedunculopontine Nucleus ◽  
Dopamine Neurons ◽  
Dopaminergic Pathway ◽  
Stimulation Of

Dopamine neurons are classically known to modulate locomotion indirectly through ascending projections to the basal ganglia that project down to brainstem locomotor networks. Their loss in Parkinson’s disease is devastating. In lampreys, we recently showed that brainstem networks also receive direct descending dopaminergic inputs that potentiate locomotor output. Here, we provide evidence that this descending dopaminergic pathway is conserved to higher vertebrates, including mammals. In salamanders, dopamine neurons projecting to the striatum or brainstem locomotor networks were partly intermingled. Stimulation of the dopaminergic region evoked dopamine release in brainstem locomotor networks and concurrent reticulospinal activity. In rats, some dopamine neurons projecting to the striatum also innervated the pedunculopontine nucleus, a known locomotor center, and stimulation of the dopaminergic region evoked pedunculopontine dopamine release in vivo. Finally, we found dopaminergic fibers in the human pedunculopontine nucleus. The conservation of a descending dopaminergic pathway across vertebrates warrants re-evaluating dopamine’s role in locomotion.

scholarly journals Synaptotagmin-1 is the Ca2+ sensor for fast striatal dopamine release

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Aditi Banerjee ◽  
Jinoh Lee ◽  
Paulina Nemcova ◽  
Changliang Liu ◽  
Pascal S Kaeser
Keyword(s):  
Dopamine Release ◽  
Brain Slices ◽  
Conditional Knockout ◽  
Dopamine Neurons ◽  
Cellular Functions ◽  
Synaptotagmin 1 ◽  
Molecular Machinery ◽  
Asynchronous Release ◽  
Secretory System

Dopamine powerfully controls neural circuits through neuromodulation. In the vertebrate striatum, dopamine adjusts cellular functions to regulate behaviors across broad time scales, but how the dopamine secretory system is built to support fast and slow neuromodulation is not known. Here, we set out to identify Ca2+-triggering mechanisms for dopamine release. We find that synchronous dopamine secretion is abolished in acute brain slices of conditional knockout mice in which Synaptotagmin-1 is removed from dopamine neurons. This indicates that Synaptotagmin-1 is the Ca2+ sensor for fast dopamine release. Remarkably, dopamine release induced by strong depolarization and asynchronous release during stimulus trains are unaffected by Synaptotagmin-1 knockout. Microdialysis further reveals that these modes and action potential-independent release provide significant amounts of extracellular dopamine in vivo. We propose that the molecular machinery for dopamine secretion has evolved to support fast and slow signaling modes, with fast release requiring the Ca2+ sensor Synaptotagmin-1.

scholarly journals The tectonigral pathway regulates appetitive locomotion in predatory hunting in mice

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Meizhu Huang ◽  
Dapeng Li ◽  
Xinyu Cheng ◽  
Qing Pei ◽  
Zhiyong Xie ◽  
...  
Keyword(s):  
Substantia Nigra ◽  
Superior Colliculus ◽  
Dopamine Release ◽  
Dorsal Striatum ◽  
Dopamine Neurons ◽  
Substantia Nigra Pars Compacta ◽  
Neuronal Circuitry ◽  
Locomotion Speed ◽  
Brain Circuit ◽  
Goal Directed Behavior

AbstractAppetitive locomotion is essential for animals to approach rewards, such as food and prey. The neuronal circuitry controlling appetitive locomotion is unclear. In a goal-directed behavior—predatory hunting, we show an excitatory brain circuit from the superior colliculus (SC) to the substantia nigra pars compacta (SNc) to enhance appetitive locomotion in mice. This tectonigral pathway transmits locomotion-speed signals to dopamine neurons and triggers dopamine release in the dorsal striatum. Synaptic inactivation of this pathway impairs appetitive locomotion but not defensive locomotion. Conversely, activation of this pathway increases the speed and frequency of approach during predatory hunting, an effect that depends on the activities of SNc dopamine neurons. Together, these data reveal that the SC regulates locomotion-speed signals to SNc dopamine neurons to enhance appetitive locomotion in mice.

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