Age-Dependent Modulation of Layer V Pyramidal Neuron Excitability in the Mouse Primary Motor Cortex by D1 Receptor Agonists and Antagonists

Abstract

The primary motor cortex (M1) receives dopaminergic (DAergic) projections from the midbrain which play a key role in modulating motor and cognitive processes, such as motor skill learning. However, little is known at the level of individual neurons about how dopamine (DA) and its receptors modulate the intrinsic properties of the different neuronal subpopulations in M1 and if this modulation depends on age. Using immunohistochemistry, we first mapped the cells expressing the DA D1 receptor across the different layers in M1, and quantified the number of pyramidal neurons (PNs) expressing the D1 receptor in the different layers, in young and adult mice. This work reveals that the spatial distribution and the molecular profile of D1 receptor-expressing neurons (D1+) across M1 layers do not change with age. Then, combining whole-cell patch-clamp recordings and pharmacology, we explored ex vivo in young and adult mice the impact of activation or blockade of D1 receptors on D1+ PN intrinsic properties. While the bath application of the D1 receptor agonist induced an increase in the excitability of layer V PNs both in young and adult, we identified a distinct modulation of intrinsic electrical properties of layer V D1+ PNs by D1 receptor antagonist depending on the age of the animal.

Keywords: D1 receptor; dopamine; excitability; primary motor cortex; pyramidal neurons.