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Michael P. Nusbaum, Ph.D

Michael P. Nusbaum, Ph.D

faculty photo
Professor of Neuroscience
Department: Neuroscience
Graduate Group Affiliations

Contact information
Dept. of Neuroscience
Perelman School of Medicine
University of Pennsylvania
120 Johnson Pavilion
Philadelphia, PA 19104-6060
Office: 215-898-1585
Fax: 215-573-9050
Lab: 215-898-9158
Education:
B.A. (History)
SUNY at Buffalo , 1973.
B.A. (Biology)
Univ. of Colorado, Boulder, 1978.

Summer Research Course- Cold Spring Harbor Lab: Leech Nervous System, 1979.
Ph.D. (Neurobiology)
University of California at San Diego, 1984.
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Description of Research Expertise

RESEARCH INTERESTS
Neural network modulation; motor pattern selection from multifunctional networks; local, presynaptic influences; neuropeptide function, cotransmission, sensory influence on central neuronal networks

KEY WORDS:
Neuromodulation; neural networks; neuropeptides; identified neurons; cotransmission

RESEARCH TECHNIQUES
Intrasomatic and intra-axonal recordings, extracellular recordings, intracellular dye injections, neurotransmitter immunocytochemistry; exogenous application of modulatory transmitters; confocal microscopy

RESEARCH SUMMARY
We aim to elucidate the many means by which nervous system provides extensive flexibility to the output of individual neuronal networks, making them “multi-functional” constructs. Currently, we are:
(1) Continuing our long-term study of the cellular and synaptic mechanisms by which different identified modulatory neurons and hormones differentially influence the same network. This includes determining the roles of co-released small molecule and neuropeptide transmitters in this process.
(2) Pursuing two new studies which target (a) the effect of behavioral (feeding) state-dependent hormonal modulation on network output, and (b) the extent to which behaviorally-relevant co-modulation of network activity is informed by studies of the individual actions of each co-modulator. Surprisingly, despite the fact that the modulation of neural networks has been studied for nearly 40 years, and that co-modulation is the likely norm by which networks are influenced in vivo, there is a dearth of data in the literature regarding the impact of co-modulation on neural network activity.

We address these issues in a small and well-defined model system, the crab (Cancer borealis) stomatogastric nervous system (STNS). The STNS is an extension of the CNS that controls the rhythmic movements of the oesophagus (swallowing) and 3-compartment stomach (food storage, chewing, pumping/filtering of chewed food). It is composed of 4 interconnected ganglia which contain several distinct, albeit interacting, rhythmically active networks which control the different foregut regions. The two networks that we study (gastric mill and pyloric networks) are located in the stomatogastric ganglion (STG), which contains only 26 neurons, most of which participate in the gastric mill and/or pyloric networks. These networks generate the gastric mill (chewing) and pyloric (pumping/filtering of chewed food) motor patterns, respectively.

The STNS is a pre-eminent model system for elucidating a cellular-level understanding of neuronal network operation. All of the STG network neurons are readily recorded intracellularly, they are all physiologically identified, their neurotransmitters and many of their membrane properties are known, and the connectomes are long-established. More than a dozen modulatory transmitters have been localized in projection neuron inputs to the STG from the other STNS ganglia, and an even larger number of peptide hormone modulators are identified in this system. When applied individually, many of these substances elicit distinct versions of the gastric mill and/or pyloric rhythm. Activating different identified modulatory neurons, or the same neurons via distinct input pathways, also elicits distinct rhythms. The unrivaled, detailed STG data library of the circuit consequences of neuromodulation provides an outstanding opportunity to address the 3 issues elucidated above.

The results of our studies will likely resonate with that in other systems insofar as, repeatedly over the past ~45 years, concepts first or most extensively established from studies in the STNS has led to general principles of neural circuit dynamics across many other biological systems, from other invertebrates to the mammalian systems.

Selected Publications

Kintos N, Nusbaum MP, Nadim F: Convergent neuromodulation onto a network neuron can have divergent effects at the network level. J. Comput. Neurosci. In Press, 2016.

McCormick DA, Nusbaum MP: Editorial Overview: Neuromodulation: Tuning the properties of neurons, networks and behavior. Curr. Opin. Neurobiol. 29: iv - vii, 2014.

Diehl F, White RS, Stein W, Nusbaum MP: Motor circuit-specific burst patterns drive different muscle and behavior patterns. Journal of Neuroscience 33: 12013-12029. 2013.

Rodriguez JC, Blitz DM, Nusbaum MP : Convergent rhythm generation from divergent cellular mechanisms. Journal of Neuroscience 33: 18047-18064, 2013.

Blitz DM, Nusbaum MP: Modulation of circuit feedback specifies motor circuit output. Journal of Neuroscience 32: 9182-9193. 2012.

Nusbaum MP, Blitz DM : Neuropeptide modulation of microcircuits. Current Opinion in Neurobiology 22: 592 - 601. 2012.

Hui L, Zhang Y, Wang J, Cook A, Hui Y, Nusbaum MP, Li L: Discovery and functional study of a novel crustacean tachykinin neuropeptide. ACS Chemical Neuroscience 2: 711-722. 2011.

Blitz DM, Nusbaum MP : Neural circuit flexibility in a small sensorimotor system. Current Opinion in Neurobiology 21: 544-552. 2011.

White RS, Nusbaum MP : The same core rhythm generator underlies different rhythmic motor patterns. Journal of Neuroscience. 31: 11484-11494, 2011.

Nusbaum MP : Regulating peptidergic modulation of rhythmically active neural circuits. Brain Behavior and Evolution 60: 378-87, 2002.

Nusbaum MP, Beenhakker MP: A small-systems approach to motor pattern generation. Nature 417: 343-50, 2002.

Nusbaum MP, Blitz DM, Swensen AM, Wood DE, Marder E : The roles of cotransmission in neural network modulation. Trends Neurosci 24: 146-54, 2001.

Blitz Dawn M, Nusbaum Michael P: State-dependent presynaptic inhibition regulates central pattern generator feedback to descending inputs. The Journal of neuroscience : the official journal of the Society for Neuroscience 28(38): 9564-74, Sep 2008.

Blitz Dawn M, White Rachel S, Saideman Shari R, Cook Aaron, Christie Andrew E, Nadim Farzan, Nusbaum Michael P: A newly identified extrinsic input triggers a distinct gastric mill rhythm via activation of modulatory projection neurons. The Journal of experimental biology 211(Pt 6): 1000-11, Mar 2008.

Beenhakker Mark P, Kirby Matthew S, Nusbaum Michael P: Mechanosensory gating of proprioceptor input to modulatory projection neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 27(52): 14308-16, Dec 2007.

Kintos Nickolas, Nusbaum Michael P, Nadim Farzan: A modeling comparison of projection neuron- and neuromodulator-elicited oscillations in a central pattern generating network. Journal of computational neuroscience 24(3): 374-97, Jun 2008.

Kirby Matthew S, Nusbaum Michael P: Peptide hormone modulation of a neuronally modulated motor circuit. Journal of neurophysiology 98(6): 3206-20, Dec 2007.

Stein Wolfgang, DeLong Nicholas D, Wood Debra E, Nusbaum Michael P: Divergent co-transmitter actions underlie motor pattern activation by a modulatory projection neuron. The European journal of neuroscience 26(5): 1148-65, Sep 2007.

Saideman Shari R, Blitz Dawn M, Nusbaum Michael P: Convergent motor patterns from divergent circuits. The Journal of neuroscience : the official journal of the Society for Neuroscience 27(25): 6664-74, Jun 2007.

Kirby Matthew S, Nusbaum Michael P: Central nervous system projections to and from the commissural ganglion of the crab Cancer borealis. Cell and tissue research 328(3): 625-37, Jun 2007.

Saideman Shari R, Ma Mingming, Kutz-Naber Kimberly K, Cook Aaron, Torfs Pieter, Schoofs Liliane, Li Lingjun, Nusbaum Michael P: Modulation of rhythmic motor activity by pyrokinin peptides. Journal of neurophysiology 97(1): 579-95, Jan 2007.

Saideman Shari R, Christie Andrew E, Torfs Pieter, Huybrechts Jurgen, Schoofs Liliane, Nusbaum Michael P: Actions of kinin peptides in the stomatogastric ganglion of the crab Cancer borealis. The Journal of experimental biology 209(Pt 18): 3664-76, Sep 2006.

Beenhakker Mark P, DeLong Nicholas D, Saideman Shari R, Nadim Farzan, Nusbaum Michael P: Proprioceptor regulation of motor circuit activity by presynaptic inhibition of a modulatory projection neuron. The Journal of neuroscience : the official journal of the Society for Neuroscience 25(38): 8794-806, Sep 2005.

DeLong Nicholas D, Kirby Matthew S, Blitz Dawn M, Nusbaum Michael P: Parallel regulation of a modulator-activated current via distinct dynamics underlies comodulation of motor circuit output. The Journal of neuroscience : the official journal of the Society for Neuroscience 29(39): 12355-67, Sep 2009.

DeLong Nicholas D, Beenhakker Mark P, Nusbaum Michael P: Presynaptic inhibition selectively weakens peptidergic cotransmission in a small motor system. Journal of neurophysiology 102(6): 3492-504, Dec 2009.

DeLong Nicholas D, Nusbaum Michael P: Hormonal modulation of sensorimotor integration. The Journal of neuroscience : the official journal of the Society for Neuroscience 30(7): 2418-27, Feb 2010.

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Last updated: 01/11/2016
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