Synaptic control of sensory transduction

Sensory neurons detect stimuli such as light, touch and chemicals, and transmit these signals to the central nervous system where the information is processed and used to modify behavior. Information from different sensory organs is prioritized and integrated by the peripheral and central nervous systems so that the most essential messages in each situation get the highest preference. A fundamental part of this process is modulation of sensory neurons by chemical messengers that are detected by specific receptor proteins on the cell membranes of the sensory neurons. Such modulation may make sensory neurons more or less sensitive, depending on the chemical messenger and the types of receptors involved. My laboratory is mainly interested in modulation of sensory neurons that respond to mechanical stimuli, such as touch, vibration or position of the body. We use an exciting invertebrate animal model, a large spider that has extremely well developed mechanical sense organs all over its body. Some spider sensory neurons are so large that we can do experiments that are impossible in any vertebrate and most invertebrate preparations. We have developed several methods that have helped to investigate how these neurons work and how their sensitivity is modified by chemical messengers. Recent advances in gene sequencing technology have allowed us to determine the nucleotide sequences of all transcribed genes in the spider nervous tissue. We have identified genes that code receptor proteins that detect chemical messengers and also genes that code proteins used in intracellular signalling. This research proposal concentrates on a group of receptors that are activated by biogenic amines, octopamine and tyramine. These chemical messengers function as neurohormones, neurotransmitters and neuromodulators and affect almost all physiological processes in invertebrates, similarly to the closely related adrenergic receptors in humans. We will investigate the relationships of spider biogenic amine receptors to receptors in other animals using specialized computer software. Biogenic amine receptor signalling properties have previously been studied when the genes have been artificially expressed in immortal cells in culture. We believe that it is more important to understand how these receptors function in real living animals where the specific cellular and behavioral responses can be observed. We will use experimental tools such as intracellular recordings to learn how the information transmission in sensory neurons is modified by these chemical messengers. Optical methods help us to observe changes in intracellular concentrations of signalling molecules. They will be used to investigate the signalling pathways that are activated or inhibited by biogenic amines. Specific locations of each receptor in various sensory organs will be explored using fluorescently labeled molecular probes. We are in the process of developing a new method to genetically silence the receptor and signalling molecules, so that we can investigate how the lack of their function affects the neurons. The problems we aim to solve and combination of methods we use are unique and will provide new knowledge in a field with a broad interest. Biogenic amines are the most intensely investigated chemical messengers in invertebrates and function in similar roles to adrenaline and noradrenaline in vertebrates. In human brain, reduced octopamine concentration is a marker for Parkinson`s disease. Tyramine interferes with some antidepressants causing very high blood pressure. Invertebrate transmitter receptors are also targets of control agents, and some are harmful to wildlife and humans. Better understanding of how biogenic amines and their receptors function is vitally important.