Rewarding effects of M4 but not M3 muscarinic cholinergic receptor antgonism in the rostromedial tegmental nucleus

The rostromedial tegmental nucleus (RMTg) receives inputs from the laterodorsal tegmental and pedunculopontine tegmental nuclei, the two principle brainstem cholinergic nuclei. We tested the effects of RMTg M3 and M4 muscarinic cholinergic receptor antagonism in a conditioned place preference (CPP) paradigm in mice. RMTg infusions of the M3 muscarinic cholinergic receptor antagonist 1,1-Dimethyl-4-diphenylacetoxypiperidinium iodide (4-DAMP) do not result in the acquisition of CPP but increase locomotor activation. By contrast, RMTg infusions of the M4 muscarinic cholinergic receptor antagonist Tropicamide result in the acquisition of CPP but do not increase locomotor activation. The rewarding effects of RMTg Tropicamide infusions are dopamine-dependent as systemic pre-treatment with the broad-spectrum dopamine receptor antagonist flupenthixol prevents the acquisition of CPP induced by RMTg Tropicamide infusions. Under conditions of systemic dopamine receptor blockade, RMTg Tropicamide infusions significantly increase locomotor activation. These data provide further support for an important role of endogenous cholinergic input to the RMTg in reward function and suggest that the contributions of RMTg cholinergic input to rewarding and locomotor-activating effects involve differential contributions of RMTg M4 and M3 muscarinic receptors, respectively

Mosaic Analysis of Precursors of Nerve, Bone and Vasculature in Caudal Body and Fin of Zebrafish

This project focuses on the specific developmental origin and formation of pre-osteoblasts, vascular cells and sensory neurons in the caudal region and tail of zebrafish. Our objective is to generate genetically marked clones using transposon microinjections and to analyze fluorescent protein markers in deep body and tail cell populations. If clones are shared between the fin and deep body it is suggestive that these cells share a common progenitor cell. Zebrafish fins can serve as a model for human organogenesis because conserved genes and cell types are found in human limbs