Obesity and type 2 diabetes are closely related diseases associated with excessive weight and fat mass, and their prevalence is increasing in the populations consuming western diets. Our goal is to define the neural mechanisms that regulate food intake, body weight, and energy homeostasis.
Food seeking and eating are motivated behaviors that olfactory cues can trigger. Accordingly, a primary focus of our research is to understand the central processing of olfactory information. Significant progress has been made in understanding general mechanisms and principles of olfactory information processing at all levels of analysis - from the molecular and cellular to the circuit, system, and behavioral level. To a large extent, this progress was possible by taking advantage of comparative studies with various vertebrate and invertebrate experimental systems. Overall, these studies showed very similar blueprints of olfactory systems, not only between arthropods but also between arthropods and vertebrates. One experimental system that has served very successfully as a model to understand principles of central olfactory information processing is the insect antennal lobe.
The processing of olfactory signals in the central nervous system occurs through highly interconnected neural networks. In insects, the initial synaptic processing of olfactory input from antennae occurs in the antennal lobe, the functional equivalent of the vertebrate olfactory bulb. Key components of the olfactory network in the antennal lobe are two main types of neurons: local interneurons and projection neurons (output neurons). Both neuron types have different physiological tasks during odor processing, requiring specialized functional phenotypes.
Our group focuses on the complex synaptic connectivity between these central olfactory neurons since it ultimately determines the spatial and temporal tuning profile of (output) projection neurons to odors. We use paired whole-cell patch-clamp recordings to characterize synaptic interactions between cholinergic uniglomerular projection neurons (uPNs) and GABAergic local interneurons (LNs), both of which are key components of the insect olfactory system. We found rapid, strong excitatory synaptic connections between uPNs and LNs. The nicotinic acetylcholine receptor blocker mecamylamine blocked this rapid excitatory transmission. IPSPs, elicited by synaptic input from a presynaptic LN, were recorded in both uPNs and LNs. IPSPs were composed of both slow, sustained components and fast, transient components which were coincident with presynaptic action potentials. The fast IPSPs were blocked by the GABAA receptor chloride channel blocker picrotoxin, whereas the slow sustained IPSPs were blocked by the GABAB receptor blocker CGP-54626. This is the first study to directly show the predicted dual fast- and slow-inhibitory action of LNs, which was predicted to be key in shaping complex odor responses in the antennal lobe. We also provide the first direct characterization of rapid postsynaptic potentials coincident with presynaptic spikes between olfactory processing neurons in the antennal lobe.
Overall, our studies aim to provide a detailed functional understanding of the synaptic connections between inhibitory GABAergic type I LNs and excitatory cholinergic uPNs and pairs of type I LNs. We consider this experimental study to be an important contribution to a better understanding of olfactory information processing, as it verifies crucial hypotheses about synaptic transmission between antennal lobe neurons that form the basis of current computational models for olfactory information processing.