On the other hand, two classes of VSNs activated by the same pheromone could indicate a synergistic or additive model of neural coding. It has recently been demonstrated that pheromone concentration influences the probability of releasing check details behaviour 17 and 18••], and that

VRs are represented in the VNO at very different abundances [19]. Multiple VRs that respond to the same pheromone may have evolved as a method of recruiting more VSNs to enhance sensitivity. From the perspective of a signaller, pheromone redundancy could maximise the dissemination of socially relevant information over time and space. Consistent with this, male urinary signals with very different physiochemical properties (volatile and non-volatile) appear to elicit an aggressive behavioural response in other male mice [20]. But until recently the redundancy of these RAD001 in vitro two cues had not been tested directly. Now two studies have assessed the functional consequence of inactivating the VSNs that detect non-volatile peptides and proteins, while leaving those that detect organic volatiles intact 21 and 22•]. The aggressive response to the non-volatile cue was now lacking as expected, but the volatile cues also no longer promoted aggression even though the VSNs

that detect them were present and functional. In fact, a surprising number of behaviours were deficient in these animals (reviewed in [23]). This suggests that the circuitry downstream of different VSN populations integrate to generate male-male aggression. The behaviour released downstream of SE signalling via Vmn1r89 and/or Vmn1r85

appears to rely on similarly integrative circuitry ( Figure 1). SEs painted on the back of ovariectomized female mice did not induce mounting behaviour from males, but SEs blended with a distinct fraction of female urine did [13••]. The identity of the bioactive molecule(s) in this fraction (termed T16) remains to be identified, but it activates different VSNs from the SEs. Thus the SEs and T16 may be collectively considered a multi-component mouse pheromone produced by females in oestrus to promote male mounting. Importantly, the information coded in each component may Aprepitant be distinct and hierarchical: T16 has the potential to report the sex of the signaller, while the SEs indicates her oestrus state [13••]. It will be interesting to determine whether these signals can elicit other behaviours relevant to the information they encode, either individually or in concert with additional components. Pheromones are widely considered to release innate or ‘hardwired’ reflexive behaviours (though, curiously, the classical definition of the term does not make this distinction 1 and 2]). Innateness is typically tested experimentally by demonstrating the behaviour occurs on the very first exposure to the pheromone, and thus is not a consequence of prior olfactory conditioning [24].