scholarly journals Laterodorsal tegmentum–ventral tegmental area projections encode positive reinforcement signals

Author(s):  
Bárbara Coimbra ◽  
Ana Verónica Domingues ◽  
Carina Soares‐Cunha ◽  
Raquel Correia ◽  
Luísa Pinto ◽  
...  
Author(s):  
Hongsheng Wang ◽  
Wanpeng Cui ◽  
Wenbing Chen ◽  
Fang Liu ◽  
Zhaoqi Dong ◽  
...  

AbstractDopamine (DA) neurons in the ventral tegmental area (VTA) are critical to coping with stress. However, molecular mechanisms regulating their activity and stress-induced depression were not well understood. We found that the receptor tyrosine kinase ErbB4 in VTA was activated in stress-susceptible mice. Deleting ErbB4 in VTA or in DA neurons, or chemical genetic inhibition of ErbB4 kinase activity in VTA suppressed the development of chronic social defeat stress (CSDS)-induced depression-like behaviors. ErbB4 activation required the expression of NRG1 in the laterodorsal tegmentum (LDTg); LDTg-specific deletion of NRG1 inhibited depression-like behaviors. NRG1 and ErbB4 suppressed potassium currents of VTA DA neurons and increased their firing activity. Finally, we showed that acute inhibition of ErbB4 after stress attenuated DA neuron hyperactivity and expression of depression-like behaviors. Together, these observations demonstrate a critical role of NRG1-ErbB4 signaling in regulating depression-like behaviors and identify an unexpected mechanism by which the LDTg-VTA circuit regulates the activity of DA neurons.


2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Ji Hoon Yoo ◽  
Vivien Zell ◽  
Navarre Gutierrez-Reed ◽  
Johnathan Wu ◽  
Reed Ressler ◽  
...  

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Bárbara Coimbra ◽  
Carina Soares-Cunha ◽  
Sónia Borges ◽  
Nivaldo AP Vasconcelos ◽  
Nuno Sousa ◽  
...  

Ventral tegmental area (VTA) activity is critical for reward/reinforcement and is tightly modulated by the laterodorsal tegmentum (LDT). In utero exposure to glucocorticoids (iuGC) triggers prominent motivation deficits but nothing is known about the impact of this exposure in the LDT-VTA circuit. We show that iuGC-rats have long-lasting changes in cholinergic markers in the LDT, together with a decrease in LDT basal neuronal activity. Interestingly, upon LDT stimulation, iuGC animals present a decrease in the magnitude of excitation and an increase in VTA inhibition, as a result of a shift in the type of cells that respond to the stimulus. In agreement with LDT-VTA dysfunction, we show that iuGC animals present motivational deficits that are rescued by selective optogenetic activation of this pathway. Importantly, we also show that LDT-VTA optogenetic stimulation is reinforcing, and that iuGC animals are more susceptible to the reinforcing properties of LDT-VTA stimulation.


2007 ◽  
Vol 30 (1) ◽  
pp. 289-316 ◽  
Author(s):  
Howard L. Fields ◽  
Gregory O. Hjelmstad ◽  
Elyssa B. Margolis ◽  
Saleem M. Nicola

2017 ◽  
Vol 27 ◽  
pp. S540
Author(s):  
B. Coimbra ◽  
C. Soares-Cunha ◽  
S. Borges ◽  
N. Vasconcelos ◽  
N. Sousa ◽  
...  

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