PhD Scientific Days 2021

TT_I_L: Theoretical and Translational Medicine I. Lectures

Anatomical dissection of the connectivity between the ventral tegmental area and basal forebrain nuclei in mice

Text of the abstract

Early anatomical studies of the midbrain dopaminergic system suggested a direct connection between the dopaminergic neurons of the ventral tegmental area (VTA) and cholinergic basal forebrain nuclei (BF) which could serve as an anatomical basis for synchronized activity of these two neuromodulatory systems crucial for learning. However, these studies did not completely reveal the projection topography and target selectivity of the major neurotransmitter systems arising from the VTA and innervating the BF nuclei.
By using light and electron microscopic techniques, we aim to reveal the cell type specific connections between the VTA dopaminergic, GABAergic and glutamatergic neurons and BF nuclei.
To examine the anatomical connection of the VTA and BF, we have performed cell-type specific anterograde tracing on transgenic mouse lines to examine the projection pattern of VTA dopaminergic, glutamatergic and GABAergic neurons, respectively. Then, we would like to identify putative target celltypes in the BF by immunohistochemistry and confocal imaging. Finally, we would confirm the presence of synaptic contacts on the putative targets by electron microscopy.
We found that these cell types differentially innervate BF nuclei; the densest dopaminergic and glutamatergic innervation could be observed in the lateral part of the ventral pallidum (VP) and VTA-GABAergic fibers innervated the VP and the Diagonal Band of Broca (DBB). We found prominent VTA-glutamatergic innervation of the medial septum as well in contrast to the low density of VTA-dopaminergic fibers in that area. Moreover, we found coexpression of dopaminergic (TH) and glutamatergic (vGluT2) markers specifically in the ventral pallidum, raising the possibility of glutamatergic-dopaminergic cotransmission.
Our results suggest that a differential modulation of basal forebrain nuclei by midbrain dopaminergic system. Moreover, we discovered an area specific dopaminergic-glutamatergic coexpression pattern in the ventral pallidum suggesting differential dopaminergic modulation within this area. We hope that our results may contribute to the understanding of dopaminergic – cholinergic interactions.
This project was supported by the ÚNKP-20-3-II New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund.

University and Doctoral School

Semmelweis University, János Szentágothai Doctoral School of Neurosciences