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Degrading Enzymes (ODEs). However, their contribution to olfactory signaling in vivo is poorly understood. This is due in part to the challenge of identifying which of the dozens of antennal-expressed CYPs might inactivate a given odorant. Here, we tested a high-throughput deorphanization strategy in Drosophila to identify CYPs that are transcriptionally induced by exposure to odorants. We discovered three CYPs selectively upregulated by geranyl acetate using transcriptional profiling. Although these CYPs are broadly expressed in the antenna in non-neuronal cells, electrophysiological recordings from CYP mutants did not reveal any changes in olfactory neuron responses to this odorant. Neurons were desensitized by pre-exposing flies to the odorant, but this effect was similar in CYP mutants. Together, our data suggest that the induction of a CYP gene by an odorant does not necessarily indicate a role for that CYP in neuronal responses to that odorant. We go on to show that some CYPs have highly restricted expression patterns in the antenna, and suggest that such CYPs may be useful candidates for further studies on olfactory CYP function.

Ion channels are often modulated by auxiliary subunits. Transmembrane AMPA receptor regulatory proteins (TARPs) are auxiliary subunits for AMPA-type glutamate receptors. These receptors are responsible for much of the fast excitatory synaptic transmission in the brain, and their mobility is thought to contribute to memory storage mechanisms. Although TARPs are known to modify AMPA receptor trafficking and gating in vitro, their contribution to in vivo AMPA receptor function is less clear.By generating mice lacking multiple TARP family members, we found that TARPs are functionally redundant. Single TARP knockout mice are viable, while those lacking multiple isoforms are often lethal. Consistent with molecular redundancy, AMPA receptor transmission in cerebellar Golgi cells is unaffected in single TARP knockout mice, but nearly eliminated in double knockouts. Unexpectedly, the remaining AMPA receptors have a different subunit composition, suggesting that TARPs may preferentially traffic GluR2 containing receptors.Our studies also highlight a role for TARPs in inhibitory neurons because AMPA receptor function in cerebellar Purkinje cells and Golgi cells is reduced in TARP knockout mice. Additionally, the loss of TARPs reduces the decay time of interneuron EPSCs. This indicates that AMPA receptor biophysical properties make a significant contribution to the time course of synaptic events, even at fast-decaying interneuron synapses.Our studies investigating TARP function in vivo also led to the discovery that TARPs profoundly change AMPA receptor pharmacology. Whereas CNQX is a competitive antagonist on AMPA receptors alone, it is a partial agonist on receptors containing any member of the TARP family and elicits depolarizing currents in neurons throughout the brain. By obtaining the crystal structure of CNQX bound to the AMPA receptor ligand-binding domain, we determined that CNQX induces a small amount of domain closure. Based on our findings, we propose an expanded mo

Ion channels are often modulated by auxiliary subunits. Transmembrane AMPA receptor regulatory proteins (TARPs) are auxiliary subunits for AMPA-type glutamate receptors. These receptors are responsible for much of the fast excitatory synaptic transmission in the brain, and their mobility is thought to contribute to memory storage mechanisms. Although TARPs are known to modify AMPA receptor trafficking and gating in vitro, their contribution to in vivo AMPA receptor function is less clear.By generating mice lacking multiple TARP family members, we found that TARPs are functionally redundant. Single TARP knockout mice are viable, while those lacking multiple isoforms are often lethal. Consistent with molecular redundancy, AMPA receptor transmission in cerebellar Golgi cells is unaffected in single TARP knockout mice, but nearly eliminated in double knockouts. Unexpectedly, the remaining AMPA receptors have a different subunit composition, suggesting that TARPs may preferentially traffic GluR2 containing receptors.Our studies also highlight a role for TARPs in inhibitory neurons because AMPA receptor function in cerebellar Purkinje cells and Golgi cells is reduced in TARP knockout mice. Additionally, the loss of TARPs reduces the decay time of interneuron EPSCs. This indicates that AMPA receptor biophysical properties make a significant contribution to the time course of synaptic events, even at fast-decaying interneuron synapses.Our studies investigating TARP function in vivo also led to the discovery that TARPs profoundly change AMPA receptor pharmacology. Whereas CNQX is a competitive antagonist on AMPA receptors alone, it is a partial agonist on receptors containing any member of the TARP family and elicits depolarizing currents in neurons throughout the brain. By obtaining the crystal structure of CNQX bound to the AMPA receptor ligand-binding domain, we determined that CNQX induces a small amount of domain closure. Based on our findings, we propose an expanded mo

Diverse sensory organs, including mammalian taste buds and insect chemosensory sensilla, show a marked compartmentalization of receptor cells; however, the functional impact of this organization remains unclear. Here we show that compartmentalized Drosophila olfactory receptor neurons (ORNs) communicate with each other directly. The sustained response of one ORN is inhibited by the transient activation of a neighbouring ORN. Mechanistically, such lateral inhibition does not depend on synapses and is probably mediated by ephaptic coupling. Moreover, lateral inhibition in the periphery can modulate olfactory behaviour. Together, the results show that integration of olfactory information can occur via lateral interactions between ORNs. Inhibition of a sustained response by a transient response may provide a means of encoding salience. Finally, a CO(2)-sensitive ORN in the malaria mosquito Anopheles can also be inhibited by excitation of an adjacent ORN, suggesting a broad occurrence of lateral inhibition in insects and possible applications in insect control.

Diverse sensory organs, including mammalian taste buds and insect chemosensory sensilla, show a marked compartmentalization of receptor cells; however, the functional impact of this organization remains unclear. Here we show that compartmentalized Drosophila olfactory receptor neurons (ORNs) communicate with each other directly. The sustained response of one ORN is inhibited by the transient activation of a neighbouring ORN. Mechanistically, such lateral inhibition does not depend on synapses and is probably mediated by ephaptic coupling. Moreover, lateral inhibition in the periphery can modulate olfactory behaviour. Together, the results show that integration of olfactory information can occur via lateral interactions between ORNs. Inhibition of a sustained response by a transient response may provide a means of encoding salience. Finally, a CO(2)-sensitive ORN in the malaria mosquito Anopheles can also be inhibited by excitation of an adjacent ORN, suggesting a broad occurrence of lateral inhibition in insects and possible applications in insect control.