Abstract
Dopamine signaling in the prefrontal cortex (PFC) is important for cognitive functions, yet very little is known about the expression of the D5 class of dopamine receptors (D5Rs) in this region. To address this, we co-stained for D5Rs, pyramidal neurons (neurogranin+), putative long-range projection pyramidal neurons (SMI-32+), and several classes of inhibitory interneuron (parvalbumin+, calbindin+, calretinin+, somatostatin+) within the frontal eye field (FEF): an area within the PFC involved in the control of visual spatial attention. We then quantified the co-expression of D5Rs with markers of different cell types across different layers of the FEF. We show that: (1) D5Rs are more prevalent on pyramidal neurons than on inhibitory interneurons. (2) D5Rs are disproportionately expressed on putative long-range projecting pyramidal neurons. The disproportionately high expression of D5Rs on long-range projecting pyramidals, compared to interneurons, was particularly pronounced in layers II–III. Together these results indicate that the engagement of D5R-dependent mechanisms in the FEF varies depending on cell type and cortical layer, and suggests that non-locally projecting neurons contribute disproportionately to functions involving the D5R subtype.
Highlights
Dopamine signaling in the prefrontal cortex (PFC) is related to numerous cognitive functions including reward processing (Arias-Carrión et al, 2010), working memory (Puig et al, 2014) and attention (Noudoost and Moore, 2011a)
We examined the number of neurons per mm2 of D5R-expressing neurons in layers I, II–III, IV, V and VI of the frontal eye field (FEF) by co-staining for D5R and a pan-neuronal protein (NeuN)
We examined the proportion of NeuN+ neurons expressing D5Rs (Figure 1B)
Summary
Dopamine signaling in the prefrontal cortex (PFC) is related to numerous cognitive functions including reward processing (Arias-Carrión et al, 2010), working memory (Puig et al, 2014) and attention (Noudoost and Moore, 2011a). The distribution of D1Rs in the PFC has been well-examined, only two recent studies (Bordelon-Glausier et al, 2008; Glausier et al, 2009) have examined the expression of D5Rs in detail. In both cases the examination of the prevalence of dopamine D5 receptors on different cell classifications was mainly restricted to layer III of macaque dorsolateral prefrontal cortex (dlPFC, Area 9). An examination of D5R expression on different cell types, including subpopulations of pyramidal neurons and different interneuron classes, is informative because previous work has established that these different neuronal classes perform distinct roles in the cortical microcircuit (Kubota, 2014; Harris and Shepherd, 2015)
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