Stuart J. Firestein, PhD

The interaction of various chemicals, such as neurotransmitters, hormones, and peptides, with membrane receptors regulate the activity of all cells in the nervous system. The ways in which these substances exert their influence is known generally as signal transduction. We use the vertebrate olfactory receptor neuron as a model for investigating general principles and mechanisms of signal transduction - receptor-ligand interactions, modulation by second messengers; ion channel gating; and the long-term mechanisms of adaptation and desensitization. The olfactory neuron is uniquely suited for these studies since it is designed specifically for the detection and discrimination of a wide variety of small organic molecules, i.e., odors.

As our window on the activities of the cell, we use the patch clamp technique to measure currents through ion channels resulting from stimulation with odor ligands, manipulation of the membrane voltage, or treatment with pharmacological agents. Questions actively being pursued in the laboratory include those concerning the role of cyclic nucleotides and calcium ions in signal generation, the mechanisms that allow the cells to discriminate among as many as 2,000 odors, and the relation between olfactory receptors and other G-protein mediated receptors such as the muscarinic and adrenergic classes of receptors.

In another vein, olfactory receptors are unique among neurons for the ability to regenerate throughout an animal's life. We have developed several experimental manipulations to induce neuronal regeneration and proliferation in vivo, allowing us to harvest neurons with a known date of birth. By applying physiological techniques for cell recording, we are quantifying, in developing neurons, biophysical parameters such as the appearance of ion channels or receptors and the development of synaptic contacts.