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Kir3 channel blockade in the cerebellar cortex suppresses performance of classically conditioned Purkinje cell responses

Johansson, Fredrik LU and Hesslow, Germund LU (2020) In Scientific Reports 10(1).
Abstract

In the eyeblink conditioning paradigm, cerebellar Purkinje cells learn to respond to the conditional stimulus with an adaptively timed pause in its spontaneous firing. Evidence suggests that the pause is elicited by glutamate released from parallel fibers and acting on metabotropic receptors (mGluR7) which initiates a delayed-onset suppression of firing. We suggested that G protein activation of hyperpolarizing Kir3 channels (or ‘GIRK’, G protein-coupled inwardly-rectifying K+ channels) could be part of such a mechanism. Application of the Kir3 antagonist Tertiapin-LQ locally in the superficial layers of the cerebellar cortex in decerebrate ferrets suppressed normal performance of Purkinje cell pause... (More)

In the eyeblink conditioning paradigm, cerebellar Purkinje cells learn to respond to the conditional stimulus with an adaptively timed pause in its spontaneous firing. Evidence suggests that the pause is elicited by glutamate released from parallel fibers and acting on metabotropic receptors (mGluR7) which initiates a delayed-onset suppression of firing. We suggested that G protein activation of hyperpolarizing Kir3 channels (or ‘GIRK’, G protein-coupled inwardly-rectifying K+ channels) could be part of such a mechanism. Application of the Kir3 antagonist Tertiapin-LQ locally in the superficial layers of the cerebellar cortex in decerebrate ferrets suppressed normal performance of Purkinje cell pause responses to the conditional stimulus. Importantly, there was no detectable effect on spontaneous firing. These findings suggest that intact functioning of Kir3 channels in the cerebellar cortex is required for normal conditioned Purkinje cell responses.

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type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
10
issue
1
article number
15654
publisher
Nature Publishing Group
external identifiers
  • scopus:85091445435
  • pmid:32973240
ISSN
2045-2322
DOI
10.1038/s41598-020-72581-8
language
English
LU publication?
yes
id
eb047c61-ef19-44f4-8a16-46347d8e7387
date added to LUP
2020-10-22 12:54:43
date last changed
2024-04-03 15:52:24
@article{eb047c61-ef19-44f4-8a16-46347d8e7387,
  abstract     = {{<p>In the eyeblink conditioning paradigm, cerebellar Purkinje cells learn to respond to the conditional stimulus with an adaptively timed pause in its spontaneous firing. Evidence suggests that the pause is elicited by glutamate released from parallel fibers and acting on metabotropic receptors (mGluR7) which initiates a delayed-onset suppression of firing. We suggested that G protein activation of hyperpolarizing K<sub>ir</sub>3 channels (or ‘GIRK’, G protein-coupled inwardly-rectifying K<sup>+</sup> channels) could be part of such a mechanism. Application of the K<sub>ir</sub>3 antagonist Tertiapin-LQ locally in the superficial layers of the cerebellar cortex in decerebrate ferrets suppressed normal performance of Purkinje cell pause responses to the conditional stimulus. Importantly, there was no detectable effect on spontaneous firing. These findings suggest that intact functioning of K<sub>ir</sub>3 channels in the cerebellar cortex is required for normal conditioned Purkinje cell responses.</p>}},
  author       = {{Johansson, Fredrik and Hesslow, Germund}},
  issn         = {{2045-2322}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{Kir3 channel blockade in the cerebellar cortex suppresses performance of classically conditioned Purkinje cell responses}},
  url          = {{http://dx.doi.org/10.1038/s41598-020-72581-8}},
  doi          = {{10.1038/s41598-020-72581-8}},
  volume       = {{10}},
  year         = {{2020}},
}