PT  - JOURNAL ARTICLE
AU  - Jesse W. Richardson-Jones
AU  - Caryne P. Craige
AU  - Thanh H. Nguyen
AU  - Hank F. Kung
AU  - Alain M. Gardier
AU  - Alex Dranovsky
AU  - Denis J. David
AU  - Bruno P. Guiard
AU  - Sheryl G. Beck
AU  - René Hen
AU  - E. David Leonardo
TI  - Serotonin-1A Autoreceptors Are Necessary and Sufficient for the Normal Formation of Circuits Underlying Innate Anxiety
AID  - 10.1523/JNEUROSCI.5836-10.2011
DP  - 2011 Apr 20
TA  - The Journal of Neuroscience
PG  - 6008--6018
VI  - 31
IP  - 16
4099  - http://www.jneurosci.org/content/31/16/6008.short
4100  - http://www.jneurosci.org/content/31/16/6008.full
SO  - J. Neurosci.2011 Apr 20; 31
AB  - Identifying the factors contributing to the etiology of anxiety and depression is critical for the development of more efficacious therapies. Serotonin (5-HT) is intimately linked to both disorders. The inhibitory serotonin-1A (5-HT1A) receptor exists in two separate populations with distinct effects on serotonergic signaling: (1) an autoreceptor that limits 5-HT release throughout the brain and (2) a heteroreceptor that mediates inhibitory responses to released 5-HT. Traditional pharmacologic and transgenic strategies have not addressed the distinct roles of these two receptor populations. Here we use a recently developed genetic mouse system to independently manipulate 5-HT1A autoreceptor and heteroreceptor populations. We show that 5-HT1A autoreceptors act to affect anxiety-like behavior. In contrast, 5-HT1A heteroreceptors affect responses to forced swim stress, without effects on anxiety-like behavior. Together with our previously reported work, these results establish distinct roles for the two receptor populations, providing evidence that signaling through endogenous 5-HT1A autoreceptors is necessary and sufficient for the establishment of normal anxiety-like behavior.