NeuropharmacologyFeb 19, 2020

Potassium channels in the brain's decision area may affect working memory in Parkinson's model rats

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 3, 2026

Abstract

Activation of M-channels in the lateral habenula improved working memory performance in rats with Parkinson's disease-related lesions.

Unilateral lesions in the substantia nigra compacta caused working memory impairment and increased firing rates of lateral habenula neurons.
Dopamine levels decreased in the ventral medial prefrontal cortex following substantia nigra compacta lesions.
Activating M-channels with retigabine enhanced working memory in both sham and lesioned rats, while blocking M-channels with XE-991 impaired it.
Higher doses of M-channel blockers were required to affect working memory in substantia nigra compacta-lesioned rats compared to sham-lesioned rats.
M-channel activation reduced firing rates of lateral habenula neurons and increased dopamine and serotonin release in the ventral medial prefrontal cortex.
The effects of M-channel modulation on neuron firing and neurotransmitter release were significantly shorter in substantia nigra compacta-lesioned rats.

Simplified

Although the lateral habenula (LHb) is involved in the regulation of multiple brain functions and this region expresses abundant M-type potassium channel (M-channel) subunits Kv7.2 and Kv7.3, the role of M-channels in regulating working memory is unclear, particularly in Parkinson's disease (PD). Here we tested the effects of activation and blockade of LHb M-channels on working memory by the T-maze rewarded alternation test in rats with unilateral 6-hydroxydopamine lesions of the substantia nigra compacta (SNc). The SNc lesion induced working memory impairment, increased the firing rate of LHb neurons, decreased dopamine (DA) level in the ventral medial prefrontal cortex (vmPFC) and reduced the expression of Kv7.2 subunit in the LHb. Intra-LHb injection of M-channel activator retigabine induced enhancement of working memory in SNc sham-lesioned and SNc-lesioned rats; conversely, the injection of M-channel blocker XE-991 impaired working memory in the two groups of rats. However, doses producing significant effects in SNc-lesioned rats were higher than those in SNc sham-lesioned rats. Further, intra-LHb injection of retigabine decreased the firing rate of LHb neurons and increased release of DA and serotonin (5-HT) in the vmPFC, while XE-991 increased the firing rate and decreased DA and 5-HT release in the two groups of rats. Compared with SNc sham-lesioned rats, the duration of M-channel activation and blockade action on the firing rate of the neurons and release of DA and 5-HT was significantly shortened in SNc-lesioned rats, which was consistent with reduced expression of Kv7.2 subunit in the LHb after lesioning the SNc. Collectively, these findings suggest involvement of LHb Kv7.2 subunit-containing M-channels in working memory impairment in SNc-lesioned rats, and that enhanced or impaired working memory after activation or blockade of M-channels in the LHb is related to the changes in the firing activity of LHb neurons and DA and 5-HT release in the vmPFC.

Full Text

Full text is available at the source.

View Full Text ↗

Potassium channels in the brain's decision area may affect working memory in Parkinson's model rats

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief