@article {69336, title = {Molecular profiling of single neurons of known identity in two ganglia from the crab Cancer borealis}, journal = {Proceedings of the National Academy of Sciences}, volume = {116}, year = {2021}, month = {2021 Feb 12}, pages = {26980 - 26990}, abstract = {

Understanding circuit organization depends on identification of cell types. Recent advances in transcriptional profiling methods have enabled classification of cell types by their gene expression. While exceptionally powerful and high throughput, the ground-truth validation of these methods is difficult: If cell type is unknown, how does one assess whether a given analysis accurately captures neuronal identity? To shed light on the capabilities and limitations of solely using transcriptional profiling for cell-type classification, we performed 2 forms of transcriptional profiling{\textemdash}RNA-seq and quantitative RT-PCR, in single, unambiguously identified neurons from 2 small crustacean neuronal networks: The stomatogastric and cardiac ganglia. We then combined our knowledge of cell type with unbiased clustering analyses and supervised machine learning to determine how accurately functionally defined neuron types can be classified by expression profile alone. The results demonstrate that expression profile is able to capture neuronal identity most accurately when combined with multimodal information that allows for post hoc grouping, so analysis can proceed from a supervised perspective. Solely unsupervised clustering can lead to misidentification and an inability to distinguish between 2 or more cell types. Therefore, this study supports the general utility of cell identification by transcriptional profiling, but adds a caution: It is difficult or impossible to know under what conditions transcriptional profiling alone is capable of assigning cell identity. Only by combining multiple modalities of information such as physiology, morphology, or innervation target can neuronal identity be unambiguously determined.

}, issn = {0027-8424}, doi = {10.1073/pnas.1911413116}, url = {https://pnas.org/doi/full/10.1073/pnas.1911413116https://pnas.org/doi/pdf/10.1073/pnas.1911413116http://www.pnas.org/syndication/doi/10.1073/pnas.1911413116}, author = {Northcutt, Adam J. and Kick, Daniel R. and Otopalik, Adriane G. and Goetz, Benjamin M. and Harris, Rayna M. and Santin, Joseph M. and Hofmann, Hans A. and Marder, Eve and Schulz, David J.} } @article {69339, title = {Neuronal morphologies built for reliable physiology in a rhythmic motor circuit}, journal = {eLife}, volume = {8}, year = {2019}, month = {2019 Jan 19}, pages = {e41728}, abstract = {

It is often assumed that highly-branched neuronal structures perform compartmentalized computations. However, previously we showed that the Gastric Mill (GM) neuron in the crustacean stomatogastric ganglion (STG) operates like a single electrotonic compartment, despite having thousands of branch points and total cable length \>10 mm (Otopalik et al., 2017a; 2017b). Here we show that compact electrotonic architecture is generalizable to other STG neuron types, and that these neurons present direction-insensitive, linear voltage integration, suggesting they pool synaptic inputs across their neuronal structures. We also show, using simulations of 720 cable models spanning a broad range of geometries and passive properties, that compact electrotonus, linear integration, and directional insensitivity in STG neurons arise from their neurite geometries (diameters tapering from 10-20 {\textmu}m to \uline\< 2 {\textmu}m at their terminal tips). A broad parameter search reveals multiple morphological and biophysical solutions for achieving different degrees of passive electrotonic decrement and computational strategies in the absence of active properties.

}, keywords = {cancer borealis, electrotonus, Stomatogastric ganglion, variability, voltage Integration}, issn = {2050-084X}, doi = {10.7554/eLife.41728}, url = {https://doi.org/10.7554/eLife.41728}, author = {Otopalik, Adriane G and Pipkin, Jason and Marder, Eve}, editor = {Slutsky, Inna and Calabrese, Ronald L} } @article {69341, title = {Sloppy morphological tuning in identified neurons of the crustacean stomatogastric ganglion}, journal = {eLife}, volume = {6}, year = {2017}, month = {2017 Feb 8}, pages = {e22352}, abstract = {

Neuronal physiology depends on a neuron{\textquoteright}s ion channel composition and unique morphology. Variable ion channel compositions can produce similar neuronal physiologies across animals. Less is known regarding the morphological precision required to produce reliable neuronal physiology. Theoretical studies suggest that moraphology is tightly tuned to minimize wiring and conduction delay of synaptic events. We utilize high-resolution confocal microscopy and custom computational tools to characterize the morphologies of four neuron types in the stomatogastric ganglion (STG) of the crab \textitCancer borealis. Macroscopic branching patterns and fine cable properties are variable within and across neuron types. We compare these neuronal structures to synthetic minimal spanning neurite trees constrained by a wiring cost equation and find that STG neurons do not adhere to prevailing hypotheses regarding wiring optimization principles. In this highly modulated and oscillating circuit, neuronal structures appear to be governed by a space-filling mechanism that outweighs the cost of inefficient wiring.

}, keywords = {cancer borealis, dendritic tree, neuronal morphology, optimization principles, wiring cost}, issn = {2050-084X}, doi = {10.7554/eLife.22352}, url = {https://doi.org/10.7554/eLife.22352}, author = {Otopalik, Adriane G and Goeritz, Marie L and Sutton, Alexander C and Brookings, Ted and Guerini, Cosmo and Marder, Eve}, editor = {Calabrese, Ronald L} } @article {69342, title = {When complex neuronal structures may not matter}, journal = {eLife}, volume = {6}, year = {2017}, month = {2017 Feb 6}, pages = {e23508}, abstract = {

Much work has explored animal-to-animal variability and compensation in ion channel expression. Yet, little is known regarding the physiological consequences of morphological variability. We quantify animal-to-animal variability in cable lengths (CV = 0.4) and branching patterns in the Gastric Mill (GM) neuron, an identified neuron type with highly-conserved physiological properties in the crustacean stomatogastric ganglion (STG) of \textitCancer borealis. We examined passive GM electrotonic structure by measuring the amplitudes and apparent reversal potentials (E\textsubscriptrevs) of inhibitory responses evoked with focal glutamate photo-uncaging in the presence of TTX. Apparent E\textsubscriptrevs were relatively invariant across sites (mean CV {\textpm} SD = 0.04 {\textpm} 0.01; 7{\textendash}20 sites in each of 10 neurons), which ranged between 100{\textendash}800 {\textmu}m from the somatic recording site. Thus, GM neurons are remarkably electrotonically compact (estimated λ \> 1.5 mm). Electrotonically compact structures, in consort with graded transmission, provide an elegant solution to observed morphological variability in the STG.

}, keywords = {electrotonus, morphology, Stomatogastric ganglion, variability, \textitCancer borealis}, issn = {2050-084X}, doi = {10.7554/eLife.23508}, url = {https://doi.org/10.7554/eLife.23508}, author = {Otopalik, Adriane G and Sutton, Alexander C and Banghart, Matthew and Marder, Eve}, editor = {Raman, Indira M} } @article {47563, title = {Complicating connectomes: Electrical coupling creates parallel pathways and degenerate circuit mechanisms.}, journal = {Developmental Neurobiology}, year = {2016}, month = {2016 Jun 17}, abstract = {

Electrical coupling in circuits can produce non-intuitive circuit dynamics, as seen in both experimental work from the crustacean stomatogastric ganglion and in computational models inspired by the connectivity in this preparation. Ambiguities in interpreting the results of electrophysiological recordings can arise if sets of pre- or postsynaptic neurons are electrically coupled, or if the electrical coupling exhibits some specificity (e.g. rectifying, or voltage-dependent). Even in small circuits, electrical coupling can produce parallel pathways that can allow information to travel by monosynaptic and/or polysynaptic pathways. Consequently, similar changes in circuit dynamics can arise from entirely different underlying mechanisms. When neurons are coupled both chemically and electrically, modifying the relative strengths of the two interactions provides a mechanism for flexibility in circuit outputs. This, together with neuromodulation of gap junctions and coupled neurons is important both in developing and adult circuits. This article is protected by copyright. All rights reserved.

}, issn = {1932-846X}, doi = {10.1002/dneu.22410}, author = {Marder, Eve and Gutierrez, Gabrielle and Nusbaum, Michael P} } @article {47559, title = {Complicating connectomes: Electrical coupling creates parallel pathways and degenerate circuit mechanisms.}, journal = {Developmental Neurobiology}, year = {2016}, month = {2016 Jun 17}, abstract = {

Electrical coupling in circuits can produce non-intuitive circuit dynamics, as seen in both experimental work from the crustacean stomatogastric ganglion and in computational models inspired by the connectivity in this preparation. Ambiguities in interpreting the results of electrophysiological recordings can arise if sets of pre- or postsynaptic neurons are electrically coupled, or if the electrical coupling exhibits some specificity (e.g. rectifying, or voltage-dependent). Even in small circuits, electrical coupling can produce parallel pathways that can allow information to travel by monosynaptic and/or polysynaptic pathways. Consequently, similar changes in circuit dynamics can arise from entirely different underlying mechanisms. When neurons are coupled both chemically and electrically, modifying the relative strengths of the two interactions provides a mechanism for flexibility in circuit outputs. This, together with neuromodulation of gap junctions and coupled neurons is important both in developing and adult circuits. This article is protected by copyright. All rights reserved.

}, issn = {1932-846X}, doi = {10.1002/dneu.22410}, author = {Marder, Eve and Gutierrez, Gabrielle and Nusbaum, Michael P} } @article {69344, title = {Quantitative Reevaluation of the Effects of Short- and Long-Term Removal of Descending Modulatory Inputs on the Pyloric Rhythm of the Crab, Cancer borealis }, journal = {eneuro}, volume = {2}, year = {2015}, month = {2015 Jan 14}, pages = {ENEURO.0058-14.2015}, abstract = {

The crustacean stomatogastric ganglion (STG) receives descending neuromodulatory inputs from three anterior ganglia: the paired commissural ganglia (CoGs), and the single esophageal ganglion (OG). In this paper, we provide the first detailed and quantitative analyses of the short- and long-term effects of removal of these descending inputs (decentralization) on the pyloric rhythm of the STG. Thirty minutes after decentralization, the mean frequency of the pyloric rhythm dropped from 1.20 Hz in control to 0.52 Hz. Whereas the relative phase of pyloric neuron activity was approximately constant across frequency in the controls, after decentralization this changed markedly. Nine control preparations kept for 5{\textendash}6 d\ in vitro\ maintained pyloric rhythm frequencies close to their initial values. Nineteen decentralized preparations kept for 5{\textendash}6 d dropped slightly in frequency from those seen at 30 min following decentralization, but then displayed stable activity over 6 d. Bouts of higher frequency activity were intermittently seen in both control and decentralized preparations, but the bouts began earlier and were more frequent in the decentralized preparations. Although the bouts may indicate that the removal of the modulatory inputs triggered changes in neuronal excitability, these changes did not produce obvious long-lasting changes in the frequency of the decentralized preparations.

}, doi = {10.1523/ENEURO.0058-14.2015}, url = {https://www.eneuro.org/lookup/doi/10.1523/ENEURO.0058-14.2015https://syndication.highwire.org/content/doi/10.1523/ENEURO.0058-14.2015}, author = {Hamood, Albert W. and Haddad, Sara A. and Otopalik, Adriane G. and Rosenbaum, Philipp and Marder, Eve} } @article {6508, title = {Vertebrate versus invertebrate neural circuits.}, journal = {Current Biology}, volume = {23}, year = {2013}, month = {2013 Jun 17}, pages = {R504-6}, issn = {1879-0445}, author = {Katz, Paul and Grillner, Sten and Wilson, Rachel and Borst, Alexander and Greenspan, Ralph and Buzs{\'a}ki, Gy{\"o}rgy and Martin, Kevan and Marder, Eve and Kristan, William and Friedrich, Rainer and Chklovskii, Dmitri Mitya} }