Les canaux BK médient l'habituation sous jacente de la plasticité synaptique chez les rats

Aperçu: G.M.

L'accoutumance à court terme est la forme la plus fondamentale de l'apprentissage implicite. L'habituation représente également un filtre pour l'inondation de l'information sensorielle, perturbée par l'autisme, la schizophrénie et d'autres troubles psychiatriques.

Des études antérieures montrent que les canaaux BK peuvent jouer un rôle essentiel dans l'habituation. L'étude montre que l'activation du canal BK et la phosphorylation subséquente de ces canaux sont essentielles pour la dépression synaptique et que la modulation positive des canaux BK in vivo peut améliorer l'habituation à court terme. Ce mécanisme peut être ciblé pour améliorer l'habituation à court terme et donc pour améliorer potentiellement les déficits de filtrage sensoriel associés aux troubles psychiatriques.

 

J Neurosci. 2017 Mar 27. pii: 3699-16. doi: 10.1523/JNEUROSCI.3699-16.2017.

BK Channels Mediate Synaptic Plasticity Underlying Habituation in Rats

Zaman T¹, De Oliveira C¹, Smoka M¹, Narla C², Poulter MO², Schmid S³.

Author information

1

Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, N6A 5C1 Canada.

2

Physiology and Pharmacology, and Molecular Medicine Research Group, Robarts Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, N6A 5C1 Canada.

3

Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, N6A 5C1 Canada Susanne.Schmid@schulich.uwo.ca

Abstract

Habituation is a basic form of implicit learning and represents a sensory filter that is disrupted in autism, schizophrenia, and several other mental disorders. Despite extensive research in the past decades on habituation of startle and other escape responses, the underlying neural mechanisms are still not fully understood. There is evidence from previous studies indicating that BK channels might pay a critical role in habituation. We here used a wide array of approaches to test this hypothesis. We show that BK channel activation and subsequent phosphorylation of these channels are essential for synaptic depression presumably underlying startle habituation in rats, using patch-clamp recordings and voltage-sensitive dye imaging in slices. Furthermore, positive modulation of BK channels in vivo can enhance short-term habituation. Although results using different approaches do not always perfectly align, together they provide convincing evidence for a crucial role of BK channel phosphorylation in synaptic depression underlying short-term habituation of startle. We also show that this mechanism can be targeted to enhance short-term habituation and therefore to potentially ameliorate sensory filtering deficits associated with psychiatric disorders.SIGNIFICANCE STATEMENTShort-term habituation is the most fundamental form of implicit learning. Habituation also represents a filter for inundating sensory information, which is disrupted in autism, schizophrenia, and other psychiatric disorders. Habituation has been studied in different organisms and behavioral models and is thought to be caused by synaptic depression in respective pathways. The underlying molecular mechanisms, however, are poorly understood. We here identify for the first time a BK channel dependent molecular synaptic mechanism leading to synaptic depression that is crucial for habituation, and we discuss the significance of our findings for potential treatments enhancing habituation.

Copyright © 2017 the authors.

PMID: 28348135

DOI: 10.1523/JNEUROSCI.3699-16.2017