Michael P. Nusbaum, Ph.D
Perelman School of Medicine
University of Pennsylvania
120 Johnson Pavilion
Philadelphia, PA 19104-6060
SUNY at Buffalo , 1973.
Univ. of Colorado, Boulder, 1978.
Summer Research Course- Cold Spring Harbor Lab: Leech Nervous System, 1979.
University of California at San Diego, 1984.
Description of Research ExpertiseRESEARCH INTERESTS
Neural network modulation; motor pattern selection from multifunctional networks; local, presynaptic influences; neuropeptide function, cotransmission, sensory influence on central neuronal networks
Neuromodulation; neural networks; neuropeptides; identified neurons; cotransmission
Intrasomatic and intra-axonal recordings, extracellular recordings, intracellular dye injections, neurotransmitter immunocytochemistry; exogenous application of modulatory transmitters; confocal microscopy
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 PublicationsBlitz Dawn M, Christie Andrew E, Cook Aaron P, Dickinson Patsy S, Nusbaum Michael P: Similarities and differences in circuit responses to applied Gly-SIFamide and peptidergic (Gly-SIFamide) neuron stimulation. Journal of neurophysiology 121(3): 950-972, Mar 2019.
Apergis-Schoute John, Burnstock Geoffrey, Nusbaum Michael P, Parker David, Morales Miguel A, Trudeau Louis-Eric, Svensson Erik: Editorial: Neuronal Co-transmission. Frontiers in neural circuits 13: 19, 2019.
Svensson Erik, Apergis-Schoute John, Burnstock Geoffrey, Nusbaum Michael P, Parker David, Schiöth Helgi B: General Principles of Neuronal Co-transmission: Insights From Multiple Model Systems. Frontiers in neural circuits 12: 117, 2018.
White Rachel S, Spencer Robert M, Nusbaum Michael P, Blitz Dawn M: State-dependent sensorimotor gating in a rhythmic motor system. Journal of neurophysiology 118(5): 2806-2818, 11 2017.
Marder Eve, Gutierrez Gabrielle J, Nusbaum Michael P: Complicating connectomes: Electrical coupling creates parallel pathways and degenerate circuit mechanisms. Developmental neurobiology 77(5): 597-609, 05 2017.
Nusbaum Michael P, Blitz Dawn M, Marder Eve: Functional consequences of neuropeptide and small-molecule co-transmission. Nature reviews. Neuroscience 18(7): 389-403, 07 2017.
Nusbaum Michael P: Neurotransmission: peptide transmitters turn 36. The Journal of experimental biology 220(Pt 14): 2492-2494, 07 2017.
Kintos Nickolas, Nusbaum Michael P, Nadim Farzan: Convergent neuromodulation onto a network neuron can have divergent effects at the network level. Journal of computational neuroscience 40(2): 113-35, Apr 2016.
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.
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.
McCormick DA, Nusbaum MP: Editorial Overview: Neuromodulation: Tuning the properties of neurons, networks and behavior. Curr. Opin. Neurobiol. 29: iv - vii, 2014.