Department of Physiology and Biophysics
University of Colorado School of Medicine
RC1 North Tower, P18-7115
Mail Stop 8307
Aurora, CO 80045
Tel (303) 724-4523
Fax (303) 724-4501
My lab is interested in understanding mechanisms used by the brain to process olfactory cues. We focus on two structures, the olfactory bulb and the piriform cortex, asking basic questions about what neurons are present, how they are connected, and how groups of neurons work to effect a particular output for a circuit. Methodologically, we combine electrophysiological and optical recordings in brain slices, confocal microscopy, as well as computational and ultrastructural approaches. We also use transgenic/viral techniques for labeling specific cell-types and optogenetic manipulation.
One specific current research interest in the lab is in the neuropil structures that line the outer surface of the olfactory bulb, called glomeruli. Glomeruli are the site of input into the bulb from axons of olfactory sensory neurons (OSNs). These structures are an especially attractive model for understanding general circuit function in the brain, as they are quite compact, about 80 µm in diameter, and also have a dedicated population of cells with apical dendritic arbors restricted to one glomerulus. These include ~25 mitral cells, 50 tufted cells, and ~500 GABAergic periglomerular (PG) cells. A glomerulus also has a clear link to function, as each glomerulus codes for information about one odorant receptor in the nose.
In studies of the organization of synapses in glomeruli, we recently obtained one surprising finding that went against the conventional view about how OSNs signal to mitral cells. In experiments in which recordings were made simultaneously from tufted cells and mitral cells affiliated with the same glomerulus (see Figure), we found that tufted cells, but not mitral cells, displayed significant electrical signals reflecting direct transmission from OSNs. Such results have led us to propose that OSNs mainly communicate to mitral cells through a multi-step path in which tufted cells act as intermediaries. We are now attempting to understand the mechanistic basis for the weak OSN signaling onto mitral cells – is it that OSN synapses are rare or more subtle effects related to the location of the synapses with respect to shunting conductances? – while we are also trying to understand the functional relevance of these mechanisms. One possible outcome of having OSNs signal directly to tufted cells, but not mitral cells, is that the mitral cell output is much more heavily regulated than that of tufted cells.
In other studies, we are examining interactions between the olfactory bulb and downstream neurons in the piriform cortex. For example, we are testing what components of the piriform cortex circuit allow it to be tuned to specific output features of the bulb, including synchronized activity in mitral cells. Also, what is the function of cortical projections that extend back to the bulb? In these latter studies, we employ optogenetic methods to achieve selective activation of feedback projections in the bulb.
Whitesell, J. D., Sorensen, K. A., Jarvie, B. C., Hentges, S. T., and Schoppa, N. E. (2013) Inter-glomerular lateral inhibition targeted on external tufted cells in the olfactory bulb. J. Neurosci. 33: 1552-1563.
Pandipati, S. and Schoppa, N. E. (2012) Age-dependent adrenergic actions in the main olfactory bulb that could underlie an olfactory sensitive period. J. Neurophysiol. 108: 1999-2007.
Gire, D. H., Franks, K. M., Zak, J. D., Tanaka, K. F., Whitesell, J. D., Mulligan, A. A., Hen, R., Schoppa, N. E. (2012) Mitral Cells in the Olfactory Bulb Are Mainly Excited through a Multistep Signaling Path. J. Neurosci. 32: 2964-2975.
Pandipati, S., Gire, D. H., and Schoppa, N. E. (2010) Adrenergic receptor-mediated disinhibition of mitral cells triggers long-term enhancement of synchronized oscillations in the olfactory bulb. J. Neurophysiol. 104: 665-674.
Gire, D. H. and Schoppa, N. E. (2009) Control of on/off glomerular signaling by a local GABAergic microcircuit in the olfactory bulb. J. Neurosci. 29: 13454-13464.
Luna, V.M. and Schoppa, N.E. (2008) GABAergic interneurons control input-spike coupling in the piriform cortex. J. Neurosci. 28, 8851-8859.
Gire, D.H. and Schoppa, N. E. (2008) Long-term enhancement of synchronized oscillations by adrenergic receptor activation in the olfactory bulb. J. Neurophysiol 99: 2021-2025.
Schoppa, N. E. (2006) AMPA/Kainate receptors drive rapid output and precise synchrony in olfactory bulb granule cells. J. Neurosci. 26:12996-13006.
Schoppa, N. E. (2006) Synchronization of olfactory bulb mitral cells by precisely-timed inhibitory inputs. Neuron 49:271-283.
Schoppa, N. E. and Westbrook, G. L. (2002) AMPA autoreceptors drive correlated spiking in olfactory bulb glomeruli. Nature Neurosci. 5, 1194-1202.
Schoppa, N. E. and Westbrook, G. L. (2001) Glomerulus-specific synchronization of mitral cells in the olfactory bulb. Neuron 31, 639-651.
Schoppa, N. E. and Westbrook, G. L. (1999) Regulation of synaptic timing in the olfactory bulb by an A-type potassium current. Nature Neurosci. 2, 1106-1113.
Schoppa, N. E., Kinzie, J. M., Sahara, Y., Segerson, T. P., and Westbrook, G. L. (1998) Dendrodendritic inhibition in the olfactory bulb is driven by NMDA receptors. J. Neurosci. 18, 6790-6802.
Schoppa, N. E. (2010) Spike timing improves olfactory capabilities in mammals. Preview in Neuron 68: 329-331.
Schoppa, N. E. (2009) Inhibition acts globally to shape olfactory cortical tuning. Preview in Neuron 62: 750-752.
Schoppa, N.E. (2009) Making scents out of how olfactory neurons are ordered in space. Nature Neurosci. 12: 103-104.
Schoppa, N. E. (2006) A novel local circuit in the olfactory bulb involving an old short-axon cell. Preview in Neuron 49: 783-784.
Schoppa, N. E. (2005) Neurotransmitter mechanisms at dendrodendritic synapses in the olfactory bulb, Chapter in Dendritic Transmitter Release (M.Ludwig, ed., Kluwer Academic/Plenum Publisher).
Schoppa, N. E. and Urban, N. N. (2003) Dendritic processing within olfactory bulb circuits. Trends in Neuroscience 26: 501-506