Chances are you have never heard of 14,16- androstadien-3-one (AND), but you have definitely smelled it if ever you’ve caught a whiff of a sweaty jogger who mistakenly forgot his deodorant.  AND is derived from testosterone and is found in male sweat, saliva, and semen. Its exposure has been shown to increase physiological arousal in heterosexual women, but not in heterosexual men1.  In addition to behavioral differences, PET scans revealed increased bloodflow to a specific region of the hypothalamus of heterosexual women and homosexual men in response to AND.  Interestingly, that same region of the hypothalamus received increased bloodflow in response to estra-1,3,5(10),16-tetraen-3-ol (EST) in heterosexual men and homosexual women2.  EST is derived from estrogen and is found in the urine of pregnant women.  These studies suggest a specific hub of pheromone processing for which the stimulating odor is sexual orientation specific. Unfortunately, its hard to delve much deeper than that in human circuit mapping, so lets focus instead on a more tractable species for which we can at least get ideas of how sexually dimorphic odor response might occur.

In the case of the fruit fly, a single odor found on male cuticle, 11-cis-vaccenyl acetate (cVA), can induce differential behavior in males and females.  Males exhibit aggression and decreased courtship behavior while females increase their receptivity to male courtship3.  Vanessa Ruta et al. (2010) set out to explore how the same pheromone, detected by the olfactory receptor type Or67D, could produce differential behavior.  A previous study had found no functional sex differences at the level of olfactory receptor responsiveness nor in the DA1 glomerulus receiving input from Or67D-expressing neurons.  However, they did find axonal branches reaching out from the glomerulus projection neurons to the ventromedial lateral horn in male flies but not in female flies4.  It was unclear if sexual differences extended beyond the axonal arbors of DA1 projection neurons and if a full dimorphic circuit could be found.

Circuit diagrams for identified dimorphic cVA pathways in the male (top) and female (bottom).  From Ruta et al. (2010).

Circuit diagrams for identified dimorphic cVA pathways in the male (top) and female (bottom). From Ruta et al. (2010).

Ruta et al. used sequentially photoactivated GFP and electrophysiology to trace a putative circuit responsive to cVA that was different in males and females.  The difference extended further than the DA1 projection neurons and into the lateral horn where they found clusters of third order neurons in males that was not present in females.  They found that a very cVA responsive male only neuron cluster, DC1, sends axons to a male specific neuropil (the lateral triangle and SMP tract).  At this stage, other sensory input converges on the neuropil and could integrate other behaviorally relevant information.  Finally, neurons from the male specific neuropil project to the ventral nerve cord, where behavioral output is enacted. Thus, Ruta et al. found a fundamentally unique circuit in male flies which may explain differential behavior.  The differences arose after the second stage of olfactory processing and continued at every following stage.  Some next steps will be confirming that this circuit is necessary for the observed male behavior and exploring the female circuit in more detail5.

Please join us in the CNCB Large Conference room on Tuesday, March 18th at 4:00pm to learn more from Dr. Vanessa Ruta on “Defining fixed and flexible neural circuits in Drosophila.”

Dr. Richard Axel will also be visiting the UCSD Neurosciences community this week to present “Order from Disorder: Internal Representations of the Olfactory World” on Wednesday, March 19th at 4:00pm at the Dorris Neuroscience Center Auditorium of The Scripps Research Institute.

Margot Wohl is a first year student in the UCSD Neuroscience Graduate Program.  She also wrote this post about UFOs and Obama? 

Primary article:
Ruta V., Datta S.R., Vasconcelos M.L., Freeland J., Looger L.L. & Axel R. (2010). A dimorphic pheromone circuit in Drosophila from sensory input to descending output, Nature, 468 (7324) 686-690. DOI:


  1. Bensafi M, Brown WM, Tsutsui T, Mainland JD, Johnson BN, Bremner EA, Young N, Mauss I, Ray B, Gross J, et al. Sex-steroid derived compounds induce sex-specific effects on autonomic nervous system function in humans. Behav Neurosci.2003;117:1125–1134.
  2. Savic I, Berglund H, Gulyas B, Roland P. Smelling of odorous sex hormone-like compounds causes sex-differentiated hypothalamic activations in humans. Neuron.2001;31:661–668.
  3. Kurtovic A, Widmer A, Dickson BJ. A single class of olfactory neurons mediates behavioural responses to a Drosophila sex pheromone. Nature. 2007;446:542–546
  4. Datta SR, Vasconcelos ML, Ruta V, Luo S, Wong A, Demir E, Flores J, Balonze K, Dickson BJ, Axel R. The Drosophila pheromone cVA activates a sexually dimorphic neural circuit. Nature. 2008;452:473–477
  5.  Good review of odor specific sexual dimorphism: Stowers L., Logan D.W. Sexual dimorphism in olfactory signaling. Curr. Opin. Neurobiol. 2010;20:770–775

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