Nathan E. Schoppa, Ph.D. Associate Professor Department of Physiology & Biophysics
	UCD Anschutz Medical Campus RC-1 North Tower, P18-7115 PO Box 6511, Mail Stop F8307 Tel (303) 724-4523 Fax (303) 724-4501	E-mail: nathan.schoppa@ucDenver.edu Curriculum vitae BNAT program member

RESEARCH

     My lab is interested in the cellular and synaptic mechanisms in the brain and how they shape the output of neuronal circuits. Our specific focus is on two structures important in the processing of olfactory sensory information: the olfactory bulb and the piriform cortex. Our approach is basically bottom-up. We start by trying to understand the properties of single synapses, and then test how these synapses affect the behavior of single cells, interactions between pairs of cells, and finally entire neuronal circuits. Methodologically, we combine electrophysiological and optical recordings in brain slices, along with computational modeling. Ultimately our results will shed light on how the olfactory system functions normally in odor detection and discrimination, as well as what can go wrong during specific disease states.

GABAergic interneurons in the olfactory bulb
      Many of our studies in the olfactory bulb (see Figure below) examine the function of “local-circuit” interneurons that release the inhibitory neurotransmitter GABA. These cells make dendrodendritic synaptic contacts onto the main output neurons of the bulb, the mitral cells. Using whole-cell patch-clamp recordings from mitral cell-pairs, we recently showed that one of the two main classes of interneurons, called granule cells, can synchronize the activity of different mitral cells on a very rapid time-scale (< 5 ms) through GABAergic synapses. We are now exploring a number of additional issues related to this rapid synchrony, including how it depends on the spatial separation of neurons and, also, the extent to which it can undergo long-term modifications through “LTP”-like alterations. The latter could be important for enhanced odor discrimination during situations of olfactory learning.

     The other main type of GABAergic interneuron in the olfactory bulb is the periglomerular (PG) cell, which contacts mitral cells in structures called glomeruli. We believe that PG cells serve a critical “gating” function in dictating olfactory information flow, and in particular function to filter out weak input signals coming from the nose. The exact circuit mechanism appears to involve complex interactions between discrete sub-populations of ~25 mitral cells and ~500 PG cells that are affiliated with a single glomerulus. Our studies of PG cells employ both patch-clamp recordings, along with "bulk" calcium dye-loading methods that allow us to visualize the behavior of a large population of neurons at once.

[Part A of the figure above shows some of the main neuron-types in the olfactory bulb, including mitral cells (M), granule cells (G), and periglomerular cells (PG). Also shown are axons of olfactory receptor neurons (ORNs) that come from the nose. Part B shows an example of two biocytin-labeled mitral cells that were synchronized in physiological recordings. The two cells had adjacent cell bodies, but their primary dendrites went to discrete glomeruli (demarcated by rings of PG cells; see arrowheads).]

Mechanisms of reading mitral cell activity in the piriform cortex
      The piriform cortex is one of the main brain structures downstream from the olfactory bulb that receives direct synaptic inputs from mitral cells. The specific question we are now testing in this circuit is related to the fast synchrony seen in mitral cells. If mitral cell synchrony is functionally important, might there be mechanisms in the piriform cortex that prefer synchronized signals? As in the bulb, we are focusing much of our analysis of the piriform cortex on the behavior of GABAergic interneurons. To facilitate cell identification, transgenic animals are used that have GABAergic neurons specifically labeled with fluorescent markers.

Current lab colleagues
 
      

Selected Publications

• Schoppa, N.E. (2009) Making scents out of how olfactory neurons are ordered in space.  Nat Neurosci. 12, 103-104 pdf
• Luna, V.M. and Schoppa, N.E. (2008) GABAergic interneurons control input-spike coupling in the piriform cortex.  J. Neurosci. 28, 8851-8859. pdf
• 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. pdf
• Schoppa, N. E. (2006) AMPA/Kainate receptors drive rapid output and precise synchrony in olfactory bulb granule cells. J. Neurosci. 26:12996-13006. pdf
  
• Schoppa, N. E. (2006) Synchronization of olfactory bulb mitral cells by precisely-timed inhibitory inputs. Neuron 49:271-283. pdf
  
• 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 Neurosience 26, 501-506. pdf
  
• Schoppa, N. E. and Westbrook, G. L. (2002) AMPA autoreceptors drive correlated spiking in olfactory bulb glomeruli. Nature Neurosci. 5, 1194-1202. pdf
  
• Schoppa, N. E. and Westbrook, G. L. (2001) NMDA receptors turn to another channel for inhibition. Neuron 31, 877-879. pdf
  
• Schoppa, N. E. and Westbrook, G. L. (2001) Glomerulus-specific synchronization of mitral cells in the olfactory bulb. Neuron 31, 639-651. pdf
  
• Christie, J. M., Schoppa, N. E., and Westbrook, G. L. (2001) Tufted cell dendrodendritic inhibition in the olfactory bulb is dependent on NMDA receptor activity. J. Neurophysiol. 85, 169-173. pdf
  
• 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. pdf
  
• 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. pdf
  
• Schoppa, N. E. and Westbrook, G. L. (1997) Modulation of mEPSCs in olfactory bulb mitral cells by metabotropic glutamate receptors. J. Neurophysiol. 78, 1468-1475. pdf
  
• Schoppa, N. E., McCormack, K., Tanouye, M. A., and Sigworth, F. J. (1992) The size of the gating charge in wild-type and mutant Shaker potassium channels. Science 255, 1712-1715.

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