Age-dependent modulation of the excitability of layer V pyramidal neurons by dopamine D1 receptors in mices primary motor cortex

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 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 PN intrinsic properties and identified a distinct modulation of intrinsic electrical properties of layer V PNs by D1 receptors depending on the age of the animal. HighlightsO_LIThe laminar distribution in M1 of cells expressing the dopamine D1 receptor is similar in young and adult mice C_LIO_LIMost of D1R-expressing cells in M1 also express Satb2 C_LIO_LID1R activation increases M1 layer V pyramidal neurons excitability both in young and adult mice C_LIO_LIThe effect of D1R blockade on M1 layer V pyramidal neurons excitability differs between young and adult mice C_LI