TY - JOUR
T1 - Dopamine rebound-excitation theory
T2 - Putting brakes on PTSD
AU - Lee, Jason C.
AU - Wang, Lei
AU - Tsien, Joseph Zhuo
N1 - Funding Information:
This work is supported by a NIH grant (R01NS079774). We would like to thank Sandra Jackson for proof-reading.
Publisher Copyright:
© 2016 Lee, Wang and Tsien.
PY - 2016/9/27
Y1 - 2016/9/27
N2 - It is not uncommon for humans or animals to experience traumatic events in their lifetimes. However, the majority of individuals are resilient to long-term detrimental changes turning into anxiety and depression, such as post-traumatic stress disorder (PTSD). What underlying neural mechanism accounts for individual variability in stress resilience? Hyperactivity in fear circuits, such as the amygdalar system, is well-known to be the major pathophysiological basis for PTSD, much like a "stuck accelerator." Interestingly, increasing evidence demonstrates that dopamine (DA) - traditionally known for its role in motivation, reward prediction, and addiction - is also crucial in regulating fear learning and anxiety. Yet, how dopaminergic (DAergic) neurons control stress resilience is unclear, especially given that DAergic neurons have multiple subtypes with distinct temporal dynamics. Here, we propose the Rebound-Excitation Theory, which posits that DAergic neurons' rebound-excitation at the termination of fearful experiences serves as an important "brake" by providing intrinsic safety-signals to fear-processing neural circuits in a spatially and temporally controlled manner. We discuss how DAergic neuron rebound-excitation may be regulated by genetics and experiences, and how such physiological properties may be used as a brain-activity biomarker to predict and confer individual resilience to stress and anxiety.
AB - It is not uncommon for humans or animals to experience traumatic events in their lifetimes. However, the majority of individuals are resilient to long-term detrimental changes turning into anxiety and depression, such as post-traumatic stress disorder (PTSD). What underlying neural mechanism accounts for individual variability in stress resilience? Hyperactivity in fear circuits, such as the amygdalar system, is well-known to be the major pathophysiological basis for PTSD, much like a "stuck accelerator." Interestingly, increasing evidence demonstrates that dopamine (DA) - traditionally known for its role in motivation, reward prediction, and addiction - is also crucial in regulating fear learning and anxiety. Yet, how dopaminergic (DAergic) neurons control stress resilience is unclear, especially given that DAergic neurons have multiple subtypes with distinct temporal dynamics. Here, we propose the Rebound-Excitation Theory, which posits that DAergic neurons' rebound-excitation at the termination of fearful experiences serves as an important "brake" by providing intrinsic safety-signals to fear-processing neural circuits in a spatially and temporally controlled manner. We discuss how DAergic neuron rebound-excitation may be regulated by genetics and experiences, and how such physiological properties may be used as a brain-activity biomarker to predict and confer individual resilience to stress and anxiety.
KW - Dopamine
KW - Fear generalization
KW - Fear memory
KW - Post-traumatic stress disorder
KW - Stress resilience
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U2 - 10.3389/fpsyt.2016.00163
DO - 10.3389/fpsyt.2016.00163
M3 - Article
AN - SCOPUS:84991777282
SN - 1664-0640
VL - 7
JO - Frontiers in Psychiatry
JF - Frontiers in Psychiatry
IS - SEP
M1 - 163
ER -