About

Michael P. Nusbaum, Ph.D., is a Professor of Neuroscience at the Department of Neuroscience within the Perelman School of Medicine at the University of Pennsylvania. His research interests focus on neural network modulation, motor pattern selection from multifunctional networks, local and presynaptic influences, neuropeptide function, cotransmission, and sensory influence on central neuronal networks. He employs techniques such as intrasomatic and intra-axonal recordings, extracellular recordings, intracellular dye injections, neurotransmitter immunocytochemistry, exogenous application of modulatory transmitters, and confocal microscopy to elucidate the mechanisms by which the nervous system provides extensive flexibility to neuronal network outputs. His work aims to understand how nervous system modulation results in multifunctional neural networks, with a particular focus on the cellular and synaptic mechanisms by which modulatory neurons and hormones influence network activity. His research includes studying the effects of behavioral state-dependent hormonal modulation and the impact of co-modulation on neural network activity, using the crab stomatogastric nervous system as a model system. This system, composed of interconnected ganglia controlling rhythmic movements of the foregut, provides a detailed and well-established model for cellular-level understanding of neuronal network operation. His studies contribute to the broader understanding of neural circuit dynamics, with principles derived from his work in the STNS system informing research across various biological systems, from invertebrates to mammals.

Research topics

• Neuroscience
• Biology
• Medicine
• Internal medicine
• Anatomy

Selected publications

• Feeding state-specific hormonal tuning of neural circuit modulation

  Journal of Neurophysiology · 2025-07-14

  articleOpen accessSenior authorCorresponding

  We establish that a complete, natural hormonal environment (hemolymph) increases the likelihood of a neuropeptide activating the gastric mill (chewing) rhythm in the crab stomatogastric ganglion (STG). The similar action of a higher neuropeptide concentration in saline, its comparable desensitizing effect to that of neuropeptide plus hemolymph on subsequent neuropeptide applications, and the absence of that neuropeptide in hemolymph suggest one or more distinct hormones act to enhance the effectiveness of the applied peptide.

  PublisherDOI

• Perturbation-specific responses by two neural circuits generating similar activity patterns

  Current Biology · 2021-09-09 · 23 citations

  articleOpen accessSenior author
  PublisherOA PDFDOI

• Feeding state-dependent modulation of feeding-related motor patterns

  Journal of Neurophysiology · 2021-10-20 · 11 citations

  articleOpen accessSenior authorCorresponding

  Little is known about behavior-linked modulation of microcircuit activity. We show that the VCN-triggered gastric mill (chewing) and pyloric (food filtering) rhythms in the isolated crab Cancer borealis stomatogastric nervous system were changed by applying hemolymph from recently fed but not unfed crabs. This included some distinct parameter changes during each examined post-fed hemolymph time-point. These results suggest the presence of feeding-related changes in circulating hormones that regulate consummatory microcircuit activity.

  PublisherOA PDFDOI

• Mass Spectrometry Quantification, Localization, and Discovery of Feeding-Related Neuropeptides in <i>Cancer borealis</i>

  ACS Chemical Neuroscience · 2021-02-01 · 30 citations

  articleOpen access

  The crab Cancer borealis nervous system is an important model for understanding neural circuit dynamics and modulation, but the identity of neuromodulatory substances and their influence on circuit dynamics in this system remains incomplete, particularly with respect to behavioral state-dependent modulation. Therefore, we used a multifaceted mass spectrometry (MS) method to identify neuropeptides that differentiate the unfed and fed states. Duplex stable isotope labeling revealed that the abundance of 80 of 278 identified neuropeptides was distinct in ganglia and/or neurohemal tissue from fed vs unfed animals. MS imaging revealed that an additional 7 and 11 neuropeptides exhibited altered spatial distributions in the brain and the neuroendocrine pericardial organs (POs), respectively, during these two feeding states. Furthermore, de novo sequencing yielded 69 newly identified putative neuropeptides that may influence feeding state-related neuromodulation. Two of these latter neuropeptides were determined to be upregulated in PO tissue from fed crabs, and one of these two peptides influenced heartbeat in ex vivo preparations. Overall, the results presented here identify a cohort of neuropeptides that are poised to influence feeding-related behaviors, providing valuable opportunities for future functional studies.

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• Mass spectrometry profiling and quantitation of changes in circulating hormones secreted over time in Cancer borealis hemolymph due to feeding behavior

  Analytical and Bioanalytical Chemistry · 2021-06-29 · 17 citations

  articleOpen access
  PublisherOA PDFDOI

• Degenerate circuits use distinct mechanisms to respond similarly to the same perturbation

  bioRxiv (Cold Spring Harbor Laboratory) · 2020-07-26

  preprintOpen accessSenior authorCorresponding

  Abstract There is considerable flexibility embedded within neural circuits. For example, separate modulatory inputs can differently configure the same underlying circuit but these different configurations generate comparable, or degenerate, activity patterns. However, little is known about whether these mechanistically different circuits in turn exhibit degenerate responses to the same inputs. We examined this issue using the crab ( Cancer borealis ) stomatogastric nervous system, in which stimulating the modulatory projection neuron MCN1 and bath applying the neuropeptide CabPK II elicit similar gastric mill (chewing) rhythms in the stomatogastric ganglion, despite differentially configuring the same neural circuit. We showed previously that bath applying the peptide hormone CCAP or stimulating the muscle stretch-sensitive sensory neuron GPR during the MCN1-elicited gastric mill rhythm selectively prolongs the protraction or retraction phase, respectively. Here, we found that these two influences on the CabPK-rhythm elicited some unique and unexpected consequences compared to their actions on the MCN1-rhythm. For example, in contrast to its effect on the MCN1-rhythm, CCAP selectively decreased the CabPK-rhythm retraction phase and thus increased the rhythm speed, whereas the CabPK-rhythm response to stimulating GPR during the retraction phase was similar its effect on the MCN1-rhythm (i.e. prolonging retraction). Interestingly, despite the comparable GPR actions on these degenerate rhythms, the underlying synaptic mechanism was distinct. Thus, degenerate circuits do not necessarily exhibit degenerate responses to the same influence, but when they do, it can occur via different underlying mechanisms. Significance Statement Circuits generating seemingly identical behaviors are often thought to arise from identical circuit states, as that is the most parsimonious explanation. Here we take advantage of an alternate scenario wherein a well-defined circuit with known connectivity generates similar activity patterns using distinct circuit states, via known mechanisms. The same peptide hormone modulation of these distinct circuit states produced divergent activity patterns, whereas the same sensory feedback altered these circuit outputs similarly but via different synaptic pathways. The latter observation limits the insights available from comparable studies in systems lacking detailed access to the underlying circuit.

  PublisherOA PDFDOI

• Distinct Microcircuit Response to Comparable Input from a Full and Partial Projection Neuron Population

  bioRxiv (Cold Spring Harbor Laboratory) · 2020-05-03

  preprintOpen accessSenior authorCorresponding

  ABSTRACT Neuronal inputs to microcircuits are often present as multiple copies of apparently equivalent neurons. Thus far, however, little is known regarding the relative influence on microcircuit output of activating all or only some copies of such an input. We are examining this issue in the crab ( Cancer borealis ) stomatogastric ganglion, where the gastric mill (chewing) microcircuit is activated by MCN1, a paired modulatory projection neuron. Both MCN1s contain the same cotransmitters, influence the same gastric mill circuit neurons, can drive the biphasic gastric mill rhythm, and are co-activated by all identified MCN1-activating pathways. Here, we determine whether the gastric mill circuit response is equivalent when stimulating one or both MCN1s under conditions where the pair are matched to collectively fire at the same overall rate and pattern as single MCN1 stimulation. The dual MCN1 stimulations elicited more consistently coordinated rhythms, and these rhythms exhibited longer phases and cycle periods. These different outcomes from single and dual MCN1 stimulation may have resulted from the relatively modest, and equivalent, firing rate of the gastric mill neuron LG during each matched set of stimulations. The LG neuron-mediated, ionotropic inhibition of the MCN1 axon terminals is the trigger for the transition from the retraction to protraction phase. This LG neuron influence on MCN1 was more effective during the dual stimulations, where each MCN1 firing rate was half that occurring during the matched single stimulations. Thus, equivalent individual- and co-activation of a class of modulatory projection neurons will not necessarily drive equivalent microcircuit output. Summary Statement Co-stimulating both copies of an identified modulatory projection neuron at the same collective firing rate used for single copy stimulation results in distinct microcircuit output.

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• Different microcircuit responses to comparable input from a one vs. both copies of an identified projection neuron

  Journal of Experimental Biology · 2020-01-01 · 7 citations

  articleOpen accessSenior author

  ) stomatogastric ganglion, where the gastric mill (chewing) microcircuit is activated by modulatory commissural neuron 1 (MCN1), a bilaterally paired modulatory projection neuron. Both MCN1s contain the same co-transmitters, influence the same gastric mill microcircuit neurons, can drive the biphasic gastric mill rhythm, and are co-activated by all identified MCN1-activating pathways. Here, we determine whether the gastric mill microcircuit response is equivalent when stimulating one or both MCN1s under conditions where the pair are matched to collectively fire at the same overall rate and pattern as single MCN1 stimulation. The dual MCN1 stimulations elicited more consistently coordinated rhythms, and these rhythms exhibited longer phases and cycle periods. These different outcomes from single and dual MCN1 stimulation may have resulted from the relatively modest, and equivalent, firing rate of the gastric mill neuron LG (lateral gastric) during each matched set of stimulations. The LG neuron-mediated, ionotropic inhibition of the MCN1 axon terminals is the trigger for the transition from the retraction to protraction phase. This LG neuron influence on MCN1 was more effective during the dual stimulations, where each MCN1 firing rate was half that occurring during the matched single stimulations. Thus, equivalent individual- and co-activation of a class of modulatory projection neurons does not necessarily drive equivalent microcircuit output.

  PublisherOA PDFDOI

• Editorial: Neuronal Co-transmission

  Frontiers in Neural Circuits · 2019-03-26 · 9 citations

  editorialOpen access

  Neuronal co-transmission is now well-established as an aspect of nervous system function. However, this was not always the case, and acceptance of this important principle has required extensive work in a range of invertebrate and vertebrate systems (see Svensson et al. for a historical perspective). This work is reviewed in articles in this research topic, which we highlight in this Editorial.

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• Similarities and differences in circuit responses to applied Gly¹-SIFamide and peptidergic (Gly¹-SIFamide) neuron stimulation

  Journal of Neurophysiology · 2019-01-16 · 29 citations

  articleOpen accessSenior author

  Microcircuit modulation by peptides is well established, but the cellular/synaptic mechanisms whereby identified neurons with identified peptide transmitters modulate microcircuits remain unknown for most systems. Here, we describe the distribution of GYRKPPFNGSIFamide (Gly 1 -SIFamide) immunoreactivity (Gly 1 -SIFamide-IR) in the stomatogastric nervous system (STNS) of the crab Cancer borealis and the Gly 1 -SIFamide actions on the two feeding-related circuits in the stomatogastric ganglion (STG). Gly 1 -SIFamide-IR localized to somata in the paired commissural ganglia (CoGs), two axons in the nerves connecting each CoG with the STG, and the CoG and STG neuropil. We identified one Gly 1 -SIFamide-IR projection neuron innervating the STG as the previously identified modulatory commissural neuron 5 (MCN5). Brief (~10 s) MCN5 stimulation excites some pyloric circuit neurons. We now find that bath applying Gly 1 -SIFamide to the isolated STG also enhanced pyloric rhythm activity and activated an imperfectly coordinated gastric mill rhythm that included unusually prolonged bursts in two circuit neurons [inferior cardiac (IC), lateral posterior gastric (LPG)]. Furthermore, longer duration (&gt;30 s) MCN5 stimulation activated a Gly 1 -SIFamide-like gastric mill rhythm, including prolonged IC and LPG bursting. The prolonged LPG bursting decreased the coincidence of its activity with neurons to which it is electrically coupled. We also identified local circuit feedback onto the MCN5 axon terminals, which may contribute to some distinctions between the responses to MCN5 stimulation and Gly 1 -SIFamide application. Thus, MCN5 adds to the few identified projection neurons that modulate a well-defined circuit at least partly via an identified neuropeptide transmitter and provides an opportunity to study peptide regulation of electrical coupled neurons in a functional context. NEW &amp; NOTEWORTHY Limited insight exists regarding how identified peptidergic neurons modulate microcircuits. We show that the modulatory projection neuron modulatory commissural neuron 5 (MCN5) is peptidergic, containing Gly 1 -SIFamide. MCN5 and Gly 1 -SIFamide elicit similar output from two well-defined motor circuits. Their distinct actions may result partly from circuit feedback onto the MCN5 axon terminals. Their similar actions include eliciting divergent activity patterns in normally coactive, electrically coupled neurons, providing an opportunity to examine peptide modulation of electrically coupled neurons in a functional context.

  PublisherOA PDFDOI

Recent grants

• NIH Grant R01NS042813

  NIH · $2.6M · 2011

• Hormonal Tuning of Specific Circuit States from a Well-Defined Connectome

  NIH · $8.3M · 1991–2028

• NIH Grant R37NS029436

  NIH · $2.9M · 2016

• NIH Grant T32GM007517

  NIH · $11.5M · 2018

Frequent coauthors

• Dawn M. Blitz

  Miami University

  21 shared

• Eve Marder

  Brandeis University

  19 shared

• Andrew E. Christie

  18 shared

• Mark P. Beenhakker

  University of Virginia

  17 shared

• Melissa J. Coleman

  W.M. Keck Science Center

  14 shared

• Farzan Nadim

  New Jersey Institute of Technology

  13 shared

• Wolfgang Stein

  7 shared

• Matthew S. Kirby

  University of Pennsylvania

  7 shared

Education

• Postdoc, Biology

  Brandeis University

  1989

• Asst. Res. Biologist, Biology

  San Francisco State University

  1989

• PhD, Biology

  University of California, San Diego

  1984

• BA, EPO Biology

  University of Colorado Boulder

  1978

• BA, History

  University at Buffalo - The State University of New York

  1973