scholarly journals Depression of substantia nigra dopamine transmission is driven by retrograde neurotensin release and is enhanced by methamphetamine self-administration

2019 ◽  
Author(s):  
Christopher W. Tschumi ◽  
Ramaswamy Sharma ◽  
William B. Lynch ◽  
Amanda L. Sharpe ◽  
Michael J. Beckstead
Keyword(s):  
Substantia Nigra ◽  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Dopamine Neurons ◽  
Self Administration ◽  
Motivated Behavior ◽  
Neurotensin Receptors ◽  
Midbrain Dopamine ◽  
Postsynaptic Calcium

AbstractMidbrain dopamine neurons play central roles in reward learning and motivated behavior, and inhibition at somatodendritic dopamine D2 receptor (D2R) synapses blunts psychostimulant reinforcement. Release of the neuropeptide neurotensin in the midbrain increases following methamphetamine exposure and induces long-term depression of D2R synaptic currents (LTDDA), however the source of neurotensin that drives LTDDA is not known. Here we show that LTDDA is driven by neurotensin released by dopamine neurons. Optogenetic stimulation of dopamine neurons was sufficient to induce LTDDA in the substantia nigra, but not the ventral tegmental area, and was dependent on neurotensin receptors, postsynaptic calcium, and vacuolar-type H+-ATPase activity in the postsynaptic cell. Further, LTDDA was enhanced in mice that had self-administered methamphetamine. These findings reveal a novel form of signaling between dopamine neurons involving release of the peptide neurotensin, which may act as a feed forward mechanism to increase dopamine neuron excitability and methamphetamine self-administration.

Differential Modulation by Nicotine of Substantia Nigra Versus Ventral Tegmental Area Dopamine Neurons

2007 ◽  
Vol 98 (6) ◽  
pp. 3388-3396 ◽  
Author(s):  
J. Russel Keath ◽  
Michael P. Iacoviello ◽  
Lindy E. Barrett ◽  
Huibert D. Mansvelder ◽  
Daniel S. McGehee
Keyword(s):  
Substantia Nigra ◽  
Ventral Tegmental Area ◽  
Dorsal Striatum ◽  
Dopamine Neurons ◽  
Substantia Nigra Pars Compacta ◽  
Synaptic Modulation ◽  
Afferent Projections ◽  
Ventral Tegmental ◽  
Midbrain Dopamine ◽  
Da Release

Midbrain dopamine (DA) neurons are found in two nuclei, the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA). The SNc dopaminergic projections to the dorsal striatum are involved in voluntary movement and habit learning, whereas the VTA projections to the ventral striatum contribute to reward and motivation. Nicotine induces profound DA release from VTA dopamine neurons but substantially less from the SNc. Nicotinic acetylcholine receptor (nAChR) expression differs between these nuclei, but it is unknown whether there are differences in nAChR expression on the afferent projections to these nuclei. Here we have compared the nicotinic modulation of excitatory and inhibitory synaptic inputs to VTA and SNc dopamine neurons. Although nicotine enhances both the excitatory and inhibitory drive to SNc DA cells with response magnitudes similar to those seen in the VTA, the prevalence of these responses in SNc is much lower. We also found that a mixture of nAChR subtypes underlies the synaptic modulation in SNc, further distinguishing this nucleus from the VTA, where α7 nAChRs enhance glutamate inputs and non-α7 receptors enhance GABA inputs. Finally, we compared the nicotine sensitivity of DA neurons in these two nuclei and found larger response magnitudes in VTA relative to SNc. Thus the observed differences in nicotine-induced DA release from VTA and SNc are likely due to differences in nAChR expression on the afferent inputs as well as on the DA neurons themselves. This may explain why nicotine has a greater effect on behaviors associated with the VTA than the SNc.

A Possible Role of Midbrain Dopamine Neurons in Short- and Long-Term Adaptation of Saccades to Position-Reward Mapping

2004 ◽  
Vol 92 (4) ◽  
pp. 2520-2529 ◽  
Author(s):  
Yoriko Takikawa ◽  
Reiko Kawagoe ◽  
Okihide Hikosaka
Keyword(s):  
Visual Cues ◽  
Early Stage ◽  
Intermediate Stage ◽  
Saccade Latency ◽  
Dopamine Neurons ◽  
Neuronal Responses ◽  
Sensory Stimuli ◽  
Reward Delivery ◽  
Midbrain Dopamine

Dopamine (DA) neurons respond to sensory stimuli that predict reward. To understand how DA neurons acquire such ability, we trained monkeys on a one-direction-rewarded version of memory-guided saccade task (1DR) only when we recorded from single DA neurons. In 1DR, position-reward mapping was changed across blocks of trials. In the early stage of training of 1DR, DA neurons responded to reward delivery; in the later stages, they responded predominantly to the visual cue that predicted reward or no reward (reward predictor) differentially. We found that such a shift of activity from reward to reward predictor also occurred within a block of trials after position-reward mapping was altered. A main effect of long-term training was to accelerate the within-block reward-to-predictor shift of DA neuronal responses. The within-block shift appeared first in the intermediate stage, but was slow, and DA neurons often responded to the cue that indicated reward in the preceding block. In the advanced stage, the reward-to-predictor shift occurred quickly such that the DA neurons' responses to visual cues faithfully matched the current position-reward mapping. Changes in the DA neuronal responses co-varied with the reward-predictive differentiation of saccade latency both in short-term (within-block) and long-term adaptation. DA neurons' response to the fixation point also underwent long-term changes until it occurred predominantly in the first trial within a block. This might trigger a switch between the learned sets. These results suggest that midbrain DA neurons play an essential role in adapting oculomotor behavior to frequent switches in position-reward mapping.

scholarly journals Effects of Long-Term Alcohol Drinking on the Dopamine D2 Receptor: Gene Expression and Heteroreceptor Complexes in the Striatum in Rats

2018 ◽  
Vol 42 (2) ◽  
pp. 338-351 ◽  
Author(s):  
Kristin Feltmann ◽  
Dasiel Oscar Borroto-Escuela ◽  
Joëlle Rüegg ◽  
Luca Pinton ◽  
Thatiane de Oliveira Sergio ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alcohol Drinking ◽  
Dopamine D2 Receptor ◽  
Receptor Gene ◽  
D2 Receptor ◽  
Heteroreceptor Complexes ◽  
Dopamine D2 ◽  
Receptor Gene Expression
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