Characterization of Identified Dopaminergic Neurons in the Mouse Forebrain and Midbrain

Abstract:

Dopaminergic (DA) neurons play pivotal roles in diverse brain functions, spanning movement, reward processing, and sensory perception. DA neurons are most abundant in the midbrain (Substantia Nigra pars compacta, SNC, and Ventral Tegmental Area, VTA) and the olfactory bulb (OB) in the forebrain. Interestingly, a subtype of OB DA neurons is capable of regenerating throughout life, while a second class is exclusively born during embryonic development. Emerging evidence in SNC and VTA also indicates substantial heterogeneity in terms of morphology, connectivity, and function. To further investigate this heterogeneity and directly compare form and function of midbrain and forebrain DA neurons, we performed immunohistochemistry and whole-cell patch-clamp recordings in ex vivo brain slices from juvenile DAT-tdTomato mice. After confirming the penetrance and specificity of the dopamine transporter (DAT) Cre line, we compared soma shape, passive membrane properties, voltage sags and action potential firing across midbrain and forebrain DA subtypes. We found that each DA subgroup within midbrain and forebrain was highly heterogeneous, and that DA neurons across the two brain areas are also substantially different. These findings complement previous work in rats as well as gene expression and in vivo datasets, further questioning the existence of a single “dopaminergic” neuronal phenotype.