Neural temporal codes have come to dominate our way of thinking on how information is coded in the brain. When precise spike timing is found to carry information, the neural code is defined as a temporal code. In spite of the importance of temporal codes, whether behaving animals actually use this type of coding is still an unresolved question. To date studying temporal codes was technically impossible due to the inability to manipulate spike timing in behaving animals. However, very recent developments in optogenetics solved this problem. Despite these modern tools, this key question is very difficult to resolve in mammals, because the meaning of manipulating a part of a neural circuit without knowledge of the neural activity of all the neurons involved in the coding is unclear.

The fly is an ideal model system to study temporal codes because its small number of neurons allows for complete mapping of the neural activity of all the neurons involved. Since temporal codes are suggested to be involved in olfactory intensity coding, we study this process. For this we device a multidisciplinary approach of electrophysiology, functional imaging and behavior.

Neuromodulation by the principal excitatory neurotransmitter is still not fully understood. In mammals where the principal neurotransmitter is glutamate one of the reasons for this is the large variety of glutamatergic receptors. In Drosophila the principal neurotransmitter is acetylcholine which mediates neuromodulation via muscarinic receptors. There are only three Drosophila muscarinic receptors. Drosophila muscarinic type A (mAChR-A) receptor is homologous to the mammalian M1 receptor and is Gq coupled. Drosophila muscarinic type B (mAChR-B) receptor is homologous to M2R and is Gi/o coupled. The third Drosophila muscarinic type C receptor is Gq coupled, but it is not expressed in the brain. Surprisingly, very little is known about the roles of Drosophila muscarinic receptors. The Drosophila olfactory system has high expression levels of both mAChR-A and mAChR-B. In particular the antennal lobe (the first relay of olfactory processing) and the mushroom body (where olfactory learning and memory occurs). We have recently found that mAChR-A is involved in neural plasticity in both antennal lobe and mushroom body. However, the roles of mAChR-B in the Drosophila olfactory system are totally unknown.

Amyotrophic Lateral Sclerosis (ALS) is a devastating adult-onset neurodegenerative disease with no cure. Several attempts to target ALS focused on removing protein aggregates, but failed to improve disease progression. Therefore, we need to first understand the underlying neuronal basis of the disease. Motor neuron hyper and hypo excitability were suggested to underlie ALS, but to date no causal evidence exists in vivo. Using optogenetics manipulations we directly modulate hyper and hypo excitability of neurons in an ALS disease model using Drosophila and examine the effects on disease progression and neural activity.

Although years of research have examined the effects of pre synaptic active zone proteins on synaptic release, their effect on post synaptic neural coding is not thoroughly examined. Using the synapse between first order odorant receptor neurons (ORNs) and second order projection neurons (PNs) in the Drosophila olfactory system, we systematically dissect how protein function at ORN active zone affects PN neural coding and fly odor perception.