The long and the short of it – a perspective on peptidergic regulation of circuits and behaviour

Journal of Experimental Biology, Journal Year: 2018, Volume and Issue: 221(3)

Published: Feb. 1, 2018

ABSTRACT Neuropeptides are the most diverse class of chemical modulators in nervous systems. They contribute to extensive modulation circuit activity and have profound influences on animal physiology. Studies invertebrate model organisms, including fruit fly Drosophila melanogaster nematode Caenorhabditis elegans, enabled genetic manipulation peptidergic signalling, contributing an understanding how neuropeptides pattern output neural circuits underpin behavioural adaptation. Electrophysiological pharmacological analyses well-defined microcircuits, such as crustacean stomatogastric ganglion, provided detailed insights into neuropeptide functions at a cellular level. These approaches can be increasingly applied mammalian brain by focusing with defined identifiable sub-population neurons. Functional systems been underpinned systematic studies map networks. Here, we review general principles mechanistic that emerged from these studies. We also highlight some challenges remain for furthering our functional relevance modulation.

Language: Английский

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High Cell Diversity and Complex Peptidergic Signaling Underlie Placozoan Behavior

Current Biology, Journal Year: 2018, Volume and Issue: 28(21), P. 3495 - 3501.e2

Published: Oct. 18, 2018

Language: Английский

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How Gastrin-Releasing Peptide Opens the Spinal Gate for Itch

Neuron, Journal Year: 2019, Volume and Issue: 103(1), P. 102 - 117.e5

Published: May 15, 2019

Spinal transmission of pruritoceptive (itch) signals requires transneuronal signaling by gastrin-releasing peptide (GRP) produced a subpopulation dorsal horn excitatory interneurons. These neurons also express the glutamatergic marker vGluT2, raising question why glutamate alone is insufficient for spinal itch relay. Using optogenetics together with slice electrophysiology and mouse behavior, we demonstrate that baseline synaptic coupling between GRP receptor (GRPR) too weak suprathreshold excitation. Only when mimicked endogenous firing stimulated them repetitively to fire bursts action potentials did GRPR depolarize progressively become excitable neurons. but not antagonism prevented this action. Provoking itch-like behavior optogenetic activation required similar stimulation paradigms. results establish gating mechanism sustained repetitive activity presynaptic postsynaptic drive neuron output.

Language: Английский

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GABAergic inhibition in dual-transmission cholinergic and GABAergic striatal interneurons is abolished in Parkinson disease

Nature Communications, Journal Year: 2018, Volume and Issue: 9(1)

Published: April 11, 2018

Abstract We report that half striatal cholinergic interneurons are dual transmitter and GABAergic (CGINs) expressing ChAT, GAD65, Lhx7, Lhx6 mRNAs, labeled with GAD VGAT, generating monosynaptic cholinergic/GABAergic currents an inhibitory pause response. Dopamine deprivation increases CGINs ongoing activity abolishes inhibition including the cortico-striatal because of high [Cl − ] i levels. also dramatically dendritic arbors interconnections probability, suggesting formation a dense network. The NKCC1 chloride importer antagonist bumetanide, which reduces levels, restores inhibition, pause-rebound response, attenuates motor effects dopamine deprivation. Therefore, most excitatory drive is balanced by concomitant powerful impaired attenuation bumetanide cardinal features Parkinson’s disease paves way to novel therapeutic strategy based on restoration low levels inhibition.

Language: Английский

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Circuit Robustness to Temperature Perturbation Is Altered by Neuromodulators

Neuron, Journal Year: 2018, Volume and Issue: 100(3), P. 609 - 623.e3

Published: Sept. 20, 2018

Language: Английский

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