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Corticotropin-releasing factor increases Purkinje neuron excitability by modulating sodium, potassium, and Ih currents.

ABSTRACT: Corticotropin-releasing factor (CRF) is a neuromodulator closely associated with stress responses. It is synthesized and released in the central nervous system by various neurons, including neurons of the inferior olive. The targets of inferior olivary neurons, the cerebellar Purkinje neurons (PNs), are endowed with CRF receptors. CRF increases the excitability of PNs in vivo, but the biophysical mechanism is not clear. Here we examine the effect of CRF on the firing properties of PNs using acute rat cerebellar slices. CRF increased the PN firing rate, regardless of whether they were firing tonically or switching between firing and quiescent periods. Current- and voltage-clamp experiments showed that the increase in firing rate was associated with a voltage shift of the activation curve of the persistent sodium current and hyperpolarizing-activated current, as well as activation of voltage-dependent potassium current. The multiple effects on various ionic currents, which are in agreement with the possibility that activation of CRF receptors triggers several intracellular pathways, are manifested as an increase excitability of PN.

SUBMITTER: Libster AM

PROVIDER: S-EPMC6712579 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Corticotropin-releasing factor increases Purkinje neuron excitability by modulating sodium, potassium, and Ih currents.

Libster Avraham M AM Title Ben B Yarom Yosef Y

Journal of neurophysiology 20151007 6

Corticotropin-releasing factor (CRF) is a neuromodulator closely associated with stress responses. It is synthesized and released in the central nervous system by various neurons, including neurons of the inferior olive. The targets of inferior olivary neurons, the cerebellar Purkinje neurons (PNs), are endowed with CRF receptors. CRF increases the excitability of PNs in vivo, but the biophysical mechanism is not clear. Here we examine the effect of CRF on the firing properties of PNs using acut ...[more]

PMID: 26445872

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Project description:BackgroundAlthough octopamine has long been known to have major roles as both transmitter and modulator in arthropods, it has only recently been shown to be functionally important in molluscs, playing a role as a neurotransmitter in the feeding network of the snail Lymnaea stagnalis. The synaptic potentials cannot explain all the effects of octopamine-containing neurons on the feeding network, and here we test the hypothesis that octopamine is also a neuromodulator.ResultsThe excitability of the B1 and B4 motoneurons in the buccal ganglia to depolarising current clamp pulses is significantly (P < < 0.05) increased by (10 microM) octopamine, whereas the B2 motoneuron becomes significantly less excitable. The ionic currents evoked by voltage steps were recorded using 2-electrode voltage clamp. The outward current of B1, B2 and B4 motoneurons had two components, a transient IA current and a sustained IK delayed-rectifier current, but neither was modulated by octopamine in any of these three buccal neurons. The fast inward current was eliminated in sodium-free saline and so is likely to be carried by sodium ions. 10 microM octopamine enhanced this current by 33 and 45% in the B1 and B4 motoneurons respectively (P < < 0.05), but a small reduction was seen in the B2 neuron. A Hodgkin-Huxley style simulation of the B1 motoneuron confirms that a 33% increase in the fast inward current by octopamine increases the excitability markedly.ConclusionWe conclude that octopamine is also a neuromodulator in snails, changing the excitability of the buccal neurons. This is supported by the close relationship from the voltage clamp data, through the quantitative simulation, to the action potential threshold, changing the properties of neurons in a rhythmic network. The increase in inward sodium current provides an explanation for the polycyclic modulation of the feeding system by the octopamine-containing interneurons, making feeding easier to initiate and making the feeding bursts more intense.

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Corticotropin-releasing factor increases Purkinje neuron excitability by modulating sodium, potassium, and Ih currents.

Publications

Corticotropin-releasing factor increases Purkinje neuron excitability by modulating sodium, potassium, and Ih currents.

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