scholarly journals Species Differences in Somatodendritic Dopamine Transmission Determine D2-Autoreceptor-Mediated Inhibition of Ventral Tegmental Area Neuron Firing

2012 ◽  
Vol 32 (39) ◽  
pp. 13520-13528 ◽  
Author(s):  
N. A. Courtney ◽  
A. A. Mamaligas ◽  
C. P. Ford
eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Peng Zhong ◽  
Casey R Vickstrom ◽  
Xiaojie Liu ◽  
Ying Hu ◽  
Laikang Yu ◽  
...  

Dopamine neurons in the ventral tegmental area (VTA) are powerful regulators of depression-related behavior. Dopamine neuron activity is altered in chronic stress-based models of depression, but the underlying mechanisms remain incompletely understood. Here, we show that mice subject to chronic mild unpredictable stress (CMS) exhibit anxiety- and depressive-like behavior, which was associated with decreased VTA dopamine neuron firing in vivo and ex vivo. Dopamine neuron firing is governed by voltage-gated ion channels, in particular hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. Following CMS, HCN-mediated currents were decreased in nucleus accumbens-projecting VTA dopamine neurons. Furthermore, shRNA-mediated HCN2 knockdown in the VTA was sufficient to recapitulate CMS-induced depressive- and anxiety-like behavior in stress-naïve mice, whereas VTA HCN2 overexpression largely prevented CMS-induced behavioral deficits. Together, these results reveal a critical role for HCN2 in regulating VTA dopamine neuronal activity and depressive-related behaviors.


2009 ◽  
Vol 29 (42) ◽  
pp. 13344-13352 ◽  
Author(s):  
C. P. Ford ◽  
P. E. M. Phillips ◽  
J. T. Williams

2012 ◽  
Vol 108 (6) ◽  
pp. 1620-1630 ◽  
Author(s):  
James E. McCutcheon ◽  
Kelly L. Conrad ◽  
Steven B. Carr ◽  
Kerstin A. Ford ◽  
Daniel S. McGehee ◽  
...  

Adolescence may be a period of vulnerability to drug addiction. In rats, elevated firing activity of ventral tegmental area (VTA) dopamine neurons predicts enhanced addiction liability. Our aim was to determine if dopamine neurons are more active in adolescents than in adults and to examine mechanisms underlying any age-related difference. VTA dopamine neurons fired faster in adolescents than in adults as measured with in vivo extracellular recordings. Dopamine neuron firing can be divided into nonbursting (single spikes) and bursting activity (clusters of high-frequency spikes). Nonbursting activity was higher in adolescents compared with adults. Frequency of burst events did not differ between ages, but bursts were longer in adolescents than in adults. Elevated dopamine neuron firing in adolescent rats was also observed in cell-attached recordings in ex vivo brain slices. Using whole cell recordings, we found that passive and active membrane properties were similar across ages. Hyperpolarization-activated cation currents and small-conductance calcium-activated potassium channel currents were also comparable across ages. We found no difference in dopamine D2-class autoreceptor function across ages, although the high baseline firing in adolescents resulted in autoreceptor activation being less effective at silencing neurons. Finally, AMPA receptor-mediated spontaneous excitatory postsynaptic currents occurred at lower frequency in adolescents; GABAA receptor-mediated spontaneous inhibitory postsynaptic currents occurred at both lower frequency and smaller amplitude in adolescents. In conclusion, VTA dopamine neurons fire faster in adolescence, potentially because GABA tone increases as rats reach adulthood. This elevation of firing rate during adolescence is consistent with it representing a vulnerable period for developing drug addiction.


2007 ◽  
Vol 191 (3) ◽  
pp. 843-853 ◽  
Author(s):  
Giuliano Pillolla ◽  
Miriam Melis ◽  
Simona Perra ◽  
Anna Lisa Muntoni ◽  
Gian Luigi Gessa ◽  
...  

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