Modulation by Neuropeptides with Overlapping Targets Results in Functional Overlap in Oscillatory Circuit Activation

Neuromodulation lends flexibility to neural circuit operation but the general notion that different neuromodulators sculpt neural circuit activity into distinct and characteristic patterns is complicated by interindividual variability. In addition, some neuromodulators converge onto the same signali...

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Veröffentlicht in:The Journal of neuroscience 2024-01, Vol.44 (1), p.e1201232023
Hauptverfasser: Cronin, Elizabeth M, Schneider, Anna C, Nadim, Farzan, Bucher, Dirk
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Nadim, Farzan
Bucher, Dirk
description Neuromodulation lends flexibility to neural circuit operation but the general notion that different neuromodulators sculpt neural circuit activity 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 stomatogastric ganglion of male crabs, Proctolin (PROC), crustacean cardioactive peptide (CCAP), and red pigment concentrating hormone (RPCH) activate the same modulatory inward current, , 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, the circuit output in PROC was distinguishable from CCAP and RPCH, but CCAP and RPCH were not distinguishable from each other. 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 confirmed this notion by showing that blind classifications by machine learning algorithms were only moderately successful. It is commonly assumed that distinct behaviors or circuit activities can be elicited by different neuromodulators. Yet it is unknown to what extent these characteristic actions remain distinct across individuals. We use a well-studied circuit model of neuromodulation to examine the effects of three neuropeptides, each known to produce a distinct activity pattern in controlled studies. We find that, when compared across individuals, the three peptides elicit activity patterns that are either statistically indistinguishable or show too much overlap to be labeled characteristic. We ascribe this to interindividual variability and overlapping subcellular actions of the modulators. Because both
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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, the circuit output in PROC was distinguishable from CCAP and RPCH, but CCAP and RPCH were not distinguishable from each other. 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 confirmed this notion by showing that blind classifications by machine learning algorithms were only moderately successful. It is commonly assumed that distinct behaviors or circuit activities can be elicited by different neuromodulators. Yet it is unknown to what extent these characteristic actions remain distinct across individuals. 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subjects Algorithms
Animals
Brachyura - physiology
Circuits
Convergence
Crustacean cardioactive peptide
Crustaceans
Euclidean geometry
Firing pattern
Ganglia, Invertebrate - physiology
Humans
Machine learning
Male
Neuromodulation
Neurons
Neurons - physiology
Neuropeptides
Neuropeptides - metabolism
Neurotransmitter Agents - pharmacology
Peptides - pharmacology
Proctolin
Red pigments
Signal Transduction
Stomatogastric ganglion
Synapses
title Modulation by Neuropeptides with Overlapping Targets Results in Functional Overlap in Oscillatory Circuit Activation
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