It is widely believed that inhibition in the mammalian brain is mediated by GABA. Whereas glycine is considered to be the dominant inhibitory amino acid transmitter in the brain stem and spinal cord. However, a more complex picture has emerged over the past several years. Recent immunohistochemical and molecular biological studies have demonstrated that there are multiple forms of the GABA-A receptor with different functional properties. Moreover, a variety of evidence suggests that glycine may function as an inhibitory transmitter in many brain regions outside of the spinal cord, including the olfactory bulb. The olfactory bulb is an ideal model to study the diversity of inhibitory synaptic circuits. The olfactory bulb contains two primary populations of neurons, a small population of mitral/tufted cells which project to cortical structures and a much larger population of inhibitory interneurons. Thus, the vast majority of neurons in the olfactory bulb, as in other cortical structures, are inhibitory interneurons. Immunohistochemical, molecular, and physiological studies, have demonstrated that there are many different types of GABA-A receptors in the olfactory bulb. Moreover, provocative recent evidence strongly suggests that glycine also may contribute to synaptic inhibition. The broad objective of this proposal is to explore the functional diversity of the GABA-A and glycine receptors expressed in olfactory bulb neurons with a particular focus on their role in synaptic transmission. The experimental approach will combine primary culture and patch clamp recording techniques to allow us to explore the possibility of a segregated distribution of inhibitory amino acid receptors among identified olfactory bulb neurons and determine their contribution to synaptic inhibition. This information may provide further insight into both normal and pathological processes involving these transmitter systems.
