Axo-glial interactions between midbrain dopamine neurons and oligodendrocyte lineage cells in the anterior corpus callosum

Abstract

Oligodendrocyte progenitor cells (OPCs) receive synaptic innervation from glutamatergic and GABAergic axons and can be dynamically regulated by neural activity, resulting in activity-dependent changes in patterns of axon myelination. However, it remains unclear to what extent other types of neurons may innervate OPCs. Here, we provide evidence implicating midbrain dopamine neurons in the innervation of oligodendrocyte lineage cells in the anterior corpus callosum and nearby white matter tracts of male and female adult mice. Dopaminergic axon terminals were identified in the corpus callosum of DAT-Cre mice after injection of an eYFP reporter virus into the midbrain. Furthermore, fast-scan cyclic voltammetry revealed monoaminergic transients in the anterior corpus callosum, consistent with the anatomical findings. Using RNAscope, we further demonstrate that ~ 40% of Olig2 + /Pdfgra + cells and ~ 20% of Olig2 + /Pdgfra- cells in the anterior corpus callosum express Drd1 and Drd2 transcripts. These results suggest that oligodendrocyte lineage cells may respond to dopamine released from midbrain dopamine axons, which could affect myelination. Together, this work broadens our understanding of neuron-glia interactions with important implications for myelin plasticity by identifying midbrain dopamine axons as a potential regulator of corpus callosal oligodendrocyte lineage cells.

Keywords: Dopamine d1 receptor; Dopamine d2 receptor; Dopamine-glial interactions; Myelin plasticity; Oligodendrocyte progenitor cells.

Fig. 1

Characteristics of corpus callosal TH+ axons. A–A” Computational confocal sections indicate that TH+ axons do not demonstrate a clear topographical organization (arrowheads indicate branching sites). B TH+ axons make perisomatic terminations (arrowheads indicate branching sites, arrows indicate perisomatic terminations). C, C’ TH+ axons align with rows of nuclei (arrowheads indicate branching sites, arrows indicate nuclei). D Multiple TH+ axons converge onto single cells (arrow). E, E’ TH+ axons adjoin striatal and cortical regions across the dorso-ventral axis (different axons identified by arrows of different colors, arrowheads indicate branching sites)

Fig. 2

OPCs receive perisomatic inputs from TH+ axons in the anterior corpus callosum. TH+ axons make perisomatic terminations (arrowheads) with GFP + nuclei in PDGFRa-GFP reporter mice

Fig. 3

Computational confocal images demonstrate eYFP+ axons in the caudal forceps minor of the corpus callosum and external capsule of adult male DAT^cre mice. Sources of high magnification examples are indicated by white bounding boxes (A–C). Note the lack of topographical organization and the frequent occurrence of perisomatic terminations

Fig. 4

Fast-scan voltammetry reveals dopamine-like signals in the anterior corpus callosum. A–C Left panel: Cartoon showing stimulating electrode and carbon-fiber microelectrode (CFM) placement in the corpus callosum (A), corpus callosum/striatum (B) and striatum (C); A–C center panel: example traces of [DA]_o vs time evoked by 1p (light color) or 20p 20 Hz (dark color). A–C top panel: cyclic voltammograms showing oxidation (~ 620 mV) and reduction (~ 20 mV) peaks consistent with dopamine in the corpus callosum (A) and striatum (C), from the peak of the transient. (D) Summary of the ratio of peak [DA]_o following 20p 20 Hz:1p n = 5, 4 sites from 2 animals

Fig. 5

Oligodendrocyte lineage cells express dopamine receptor 1 (Drd1) and dopamine receptor 2 (Drd2) transcripts in anterior regions of the corpus callosum. Computational confocal images demonstrating DAPI (A, B); Olig2 and Drd1 (A’) or Olig2 and Drd2 (B’) RNA probes; Olig2, Pdgfra and Drd1 (A’’) or Olig2, Pdgfra and Drd2 (B’’) RNA probes; and the merge of all channels (A’’’, B’’’). Arrows indicate Olig2 + /Pdgfra + cells that colocalize with dopamine receptor transcripts. Arrowheads indicate Olig2 + /Pdgfra- cells that colocalize with dopamine receptor transcripts. C Quantification of dopamine receptor transcripts by oligodendrocyte lineage cells in the anterior corpus callosum. On average, there are nearly twofold more Olig2 + /Pdgfra + cells than Olig2 + /Pdgfra- expressing dopamine receptor transcripts (F_{(1, 11)} = 13.9, **p < .01). Each black dot represents the average of 2–4 brains sections per animal