Altered gating of K v 1.4 in the nucleus accumbens suppresses motivation for reward

Deficient motivation contributes to numerous psychiatric disorders, including withdrawal from drug use, depression, schizophrenia, and others. Nucleus accumbens (NAc) has been implicated in motivated behavior, but it remains unclear whether motivational drive is linked to discrete neurobiological me...

Full description

Saved in:
Bibliographic Details
Published in:eLife 2019-09, Vol.8
Main Authors: O'Donovan, Bernadette, Adeluyi, Adewale, Anderson, Erin L, Cole, Robert D, Turner, Jill R, Ortinski, Pavel I
Format: Article
Language:English
Subjects:
Animals
Kv1.4 Potassium Channel - metabolism
Motivation
Neurons - enzymology
Neurons - physiology
Nucleus Accumbens - physiology
Rats, Sprague-Dawley
Reward
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Deficient motivation contributes to numerous psychiatric disorders, including withdrawal from drug use, depression, schizophrenia, and others. Nucleus accumbens (NAc) has been implicated in motivated behavior, but it remains unclear whether motivational drive is linked to discrete neurobiological mechanisms within the NAc. To examine this, we profiled cohorts of Sprague-Dawley rats in a test of motivation to consume sucrose. We found that substantial variability in willingness to exert effort for reward was not associated with operant responding under low-effort conditions or stress levels. Instead, effort-based motivation was mirrored by a divergent NAc shell transcriptome with differential regulation at potassium and dopamine signaling genes. Functionally, motivation was inversely related to excitability of NAc principal neurons. Furthermore, neuronal and behavioral outputs associated with low motivation were linked to faster inactivation of a voltage-gated potassium channel, K 1.4. These results raise the prospect of targeting K 1.4 gating in psychiatric conditions associated with motivational dysfunction.
ISSN:2050-084X