Striatal Neurons Expressing D1 and D2 Receptors are Morphologically Distinct and Differently Affected by Dopamine Denervation in Mice

D Gagnon,S Petryszyn,M Parent,M G Sanchez,C Bories,A Parent,Y De Koninck,J M Beaulieu

doi:10.1038/srep41432

D Gagnon, S Petryszyn + Show 6 more

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https://doi.org/10.1038/srep41432

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Abstract

The loss of nigrostriatal dopamine neurons in Parkinson’s disease induces a reduction in the number of dendritic spines on medium spiny neurons (MSNs) of the striatum expressing D1 or D2 dopamine receptor. Consequences on MSNs expressing both receptors (D1/D2 MSNs) are currently unknown. We looked for changes induced by dopamine denervation in the density, regional distribution and morphological features of D1/D2 MSNs, by comparing 6-OHDA-lesioned double BAC transgenic mice (Drd1a-tdTomato/Drd2-EGFP) to sham-lesioned animals. D1/D2 MSNs are uniformly distributed throughout the dorsal striatum (1.9% of MSNs). In contrast, they are heterogeneously distributed and more numerous in the ventral striatum (14.6% in the shell and 7.3% in the core). Compared to D1 and D2 MSNs, D1/D2 MSNs are endowed with a smaller cell body and a less profusely arborized dendritic tree with less dendritic spines. The dendritic spine density of D1/D2 MSNs, but also of D1 and D2 MSNs, is significantly reduced in 6-OHDA-lesioned mice. In contrast to D1 and D2 MSNs, the extent of dendritic arborization of D1/D2 MSNs appears unaltered in 6-OHDA-lesioned mice. Our data indicate that D1/D2 MSNs in the mouse striatum form a distinct neuronal population that is affected differently by dopamine deafferentation that characterizes Parkinson’s disease.

Highlights

The loss of nigrostriatal dopamine neurons in Parkinson’s disease induces a reduction in the number of dendritic spines on medium spiny neurons (MSNs) of the striatum expressing D1 or D2 dopamine receptor
Using stereological approaches and single-neuronal injections performed on striatal sections from sham and 6-hydroxydopamine (6-OHDA)-lesioned double BAC transgenic mice (Drd1a-tdTomato/Drd2-EGFP), we show that the D1/D2 MSNs are affected differently than the D1 and D2 MSNs by striatal DA deafferentation that characterizes Parkinson’s disease (PD)
Immunolabeling of the striatum and the substantia nigra pars compacta (SNc) for the DA transporter (DAT) and tyrosine hydroxylase (TH) indicate a severe DA lesion caused by 6-OHDA unilateral injections performed in the medial forebrain bundle (Fig. 1)

Summary

Introduction

The loss of nigrostriatal dopamine neurons in Parkinson’s disease induces a reduction in the number of dendritic spines on medium spiny neurons (MSNs) of the striatum expressing D1 or D2 dopamine receptor. These cells form a rather morphologically homogeneous population, each element being endowed with a medium-sized cell body and typical spiny dendrites These so-called medium spiny neurons (MSNs) all use γ-aminobutyric acid (GABA) as a neurotransmitter and represent approximately 90–95% of the striatal neuronal population in rodents[1]. Half of the MSNs express dopamine (DA) receptor of the D1 type and contain the neuropeptides substance P (SP) and dynorphin (DYN) They innervate mainly the substantia nigra pars reticulata and the entopeduncular nucleus (rodent homologue of primate internal pallidum) and form the so-called “direct pathway”. The other half of the MSNs expresses DA receptor of the D2 type and contains the neuropeptide enkephalin (ENK) Their axon arborizes principally in the pallidum (rodent homologue of primate external pallidum) and forms the first segment of the so-called “indirect pathway”[2,3,4,5]. While co-expression of D1 and D2 receptors is well accepted, the existence of D1/D2 heteromers in vivo remains controversial[29,30]

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