Neuromodulation Reduces Interindividual Variability of Neuronal Output

Schneider, Anna C.; Itani, Omar; Bucher, Dirk; Nadim, Farzan

doi:10.1523/eneuro.0166-22.2022

Cited by 4 publications

(1 citation statement)

References 88 publications

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“…Ionic currents and synapses targeted by neuromodulation can vary substantially across individuals, and circuit outputs under the same conditions can show some degree of variability (Marder and Goaillard, 2006;Calabrese et al, 2011;Golowasch, 2014;Marder et al, 2014b;Goaillard and Marder, 2021). Neuromodulator receptor expression and modulatory effects on individual neurons or synapses can also be quite variable (Garcia et al, 2015;Maloney, 2021), and neuromodulation can either promote or counteract interindividual variability (Hamood and Marder, 2014;Marder et al, 2014a;Maloney, 2021;Xu et al, 2021;Schneider et al, 2022;Tamvacakis et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

Modulation by neuropeptides with overlapping targets results in functional overlap in oscillatory circuit activation

Cronin

Schneider

Nadim

et al. 2023

Preprint

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Neuromodulation lends flexibility to neural circuit operation. However, the general notion that different neuromodulators sculpt neural circuit output into distinct and characteristic patterns is complicated by interindividual variability. In addition, some neuromodulators converge onto the same signaling pathways, with similar effects on neurons and synapses. We compared the effects of three neuropeptides on the rhythmic pyloric circuit in the crab Cancer borealis stomatogastric nervous system. Proctolin (PROC), crustacean cardioactive peptide (CCAP), and red pigment concentrating hormone (RPCH) all activate the same modulatory inward current, IMI, and have convergent actions on synapses. However, while PROC targets all four neuron types in the core pyloric circuit, CCAP and RPCH target the same subset of only two neurons. After removal of spontaneous neuromodulator release, none of the neuropeptides restored the control cycle frequency, but all restored the relative timing between neuron types. Consequently, differences between neuropeptide effects were mainly found in the spiking activity of different neuron types. We performed statistical comparisons using the Euclidean distance in the multidimensional space of normalized output attributes to obtain a single measure of difference between modulatory states. Across preparations, circuit output in PROC was distinguishable from CCAP and RPCH, but CCAP and RPCH were not. However, we argue that even between PROC and the other two neuropeptides, population data overlapped enough to prevent reliable identification of individual output patterns as characteristic for a specific neuropeptide. We confirm this notion by showing that blind classifications by machine learning algorithms are only moderately successful.

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Section: Introductionmentioning

confidence: 99%

Modulation by neuropeptides with overlapping targets results in functional overlap in oscillatory circuit activation

Cronin

Schneider

Nadim

et al. 2023

Preprint

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Diversity of neuropeptidergic modulation in decapod crustacean cardiac and feeding systems

Dickinson,

Powell

2023

Current Opinion in Neurobiology

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Comodulation reduces interindividual variability of circuit output

Schneider

Itani

Cronin

et al. 2023

Preprint

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Ionic current levels of identified neurons vary substantially across individual animals. Yet, under similar conditions, neural circuit output remains remarkably similar, particularly in motor circuits. At any time, a neural circuit is influenced by multiple neuromodulators which provide flexibility to its output. These neuromodulators often overlap in their actions by modulating the same channel type or synapse yet have neuron-specific actions resulting from distinct receptor expression. With multiple neuromodulators, however, a common target is more uniformly activated across neurons. We propose that a baseline tonic (non-saturating) level of comodulation by convergent neuromodulators can reduce interindividual variability of circuit output. We tested this hypothesis in the pyloric circuit of the crab Cancer borealis. Multiple excitatory neuropeptides converge to activate the same voltage-gated inward current in this circuit, but different subsets of pyloric neurons have receptors for each peptide. We quantified the interindividual variability of the unmodulated pyloric circuit output by measuring the activity phases, cycle frequency and within-burst spike number and frequency. We then examined the variability in the presence of different combinations and concentrations of three excitatory neuropeptides. We found that at mid-level concentration (30 nM) but not at near-threshold (1 nM) or saturating (1 μM) concentrations, comodulation by multiple neuropeptides reduced the circuit output variability. Notably, the output variability of an isolated neuron was not reduced by comodulation at the mid-level concentration. Therefore, the reduction of circuit output variability is not due to a simple reduction of the variability of individual neuron excitability but emerges as a network effect.

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Neuromodulation Reduces Interindividual Variability of Neuronal Output

Abstract: Visual Abstract

Cited by 4 publications

References 88 publications

Modulation by neuropeptides with overlapping targets results in functional overlap in oscillatory circuit activation

Modulation by neuropeptides with overlapping targets results in functional overlap in oscillatory circuit activation

Diversity of neuropeptidergic modulation in decapod crustacean cardiac and feeding systems

Comodulation reduces interindividual variability of circuit output

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