Confocal analysis of cholinergic and dopaminergic inputs onto pyramidal cells in the prefrontal cortex of rodents

Zhang Zhang

doi:10.3389/fnana.2010.00021

Abstract

Cholinergic and dopaminergic projections to the rat medial prefrontal cortex (mPFC) are both involved in cognitive functions including attention. These neuronal systems modulate mPFC neuronal activity mainly through diffuse transmission. In order to better understand the anatomical level of influence of these systems, confocal microscopy with triple-fluorescent immunolabeling was used in three subregions of the mPFC of rats and Drd1a-tdTomato/Drd2-EGFP transgenic mice. The zone of interaction was defined as a reciprocal microproximity between dopaminergic and cholinergic axonal segments as well as pyramidal neurons. The density of varicosities, along these segments was considered as a possible activity-dependant morphological feature. The percentage of cholinergic and dopaminergic fibers in microproximity ranged from 12 to 40% depending on the layer and mPFC subregion. The cholinergic system appeared to have more influence on dopaminergic fibers since a larger proportion of the dopaminergic fibers were within microproximity to cholinergic fibers. The density of both cholinergic and dopaminergic varicosities was significantly elevated within microproximities. The main results indicate that the cholinergic and dopaminergic systems converge on pyramidal cells in mPFC particularly in the layer V. In transgenic mice 93% of the pyramidal cells expressed the transgenic marker for Drd2 expression, but only 22% expressed the maker for Drd1ar expression. Data presented here suggest that the modulation of mPFC by dopaminergic fibers would be mostly inhibitory and localized at the output level whereas the cholinergic modulation would be exerted at the input and output level both through direct interaction with pyramidal cells and dopaminergic fibers.

Highlights

The rat medial prefrontal cortex is involved in a variety of cognitive functions including attentional processes, working memory, behavioral flexibility and inhibition (Heidbreder and Groenewegen, 2003; Gabbott et al, 2005; Briand et al, 2007)
The density of total length of dopaminergic (TH) fibers ranged from 0.008 μm/μm3 in Cg1 to 0.020 μm/μm3 in IL, and the density of choline acetyltransferase (ChAT) fibers ranged from 0.021 μm/μm3 in Cg1 to 0.044 μm/μm3 in PrL (Table 2)
Part of the ChAT fibers could be attributed to the intracortical cholinergic neurons but this did not represent more than 10% of the fibers

Summary

Introduction

The rat medial prefrontal cortex (mPFC) is involved in a variety of cognitive functions including attentional processes, working memory, behavioral flexibility and inhibition (Heidbreder and Groenewegen, 2003; Gabbott et al, 2005; Briand et al, 2007). Its three main anatomical subdivisions, the anterior cingulate (Cg1), the prelimbic (PrL) and the infralimbic (IL) areas (Vertes, 2004, 2006; Tavares and Correa, 2006) receive long ascending projections from cholinergic neurons of the basal forebrain (BF) (Golmayo et al, 2003; Henny and Jones, 2008) and from dopaminergic neurons of the ventral tegmental area (VTA) Both neuronal systems modulate mPFC activity and attentional performance (Gill et al, 2000; Golmayo et al, 2003; Sarter et al, 2003; Chudasama et al, 2004; Dalley et al, 2004; Sarter et al, 2005; Goto et al, 2007; Del Arco and Mora, 2009). Both ACh and DA systems are involved in pathologies such as Alzheimer’s disease, attention deficit hyperactivity disorder and schizophrenia

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