Abstract
The cellular architecture of the ventral tegmental area (VTA), the main hub of the brain reward system, remains only partially characterized. To extend the characterization to inhibitory neurons, we have identified three distinct subtypes of somatostatin (Sst)-expressing neurons in the mouse VTA. These neurons differ in their electrophysiological and morphological properties, anatomical localization, as well as mRNA expression profiles. Importantly, similar to cortical Sst-containing interneurons, most VTA Sst neurons express GABAergic inhibitory markers, but some of them also express glutamatergic excitatory markers and a subpopulation even express dopaminergic markers. Furthermore, only some of the proposed marker genes for cortical Sst neurons were expressed in the VTA Sst neurons. Physiologically, one of the VTA Sst neuron subtypes locally inhibited neighboring dopamine neurons. Overall, our results demonstrate the remarkable complexity and heterogeneity of VTA Sst neurons and suggest that these cells are multifunctional players in the midbrain reward circuitry.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
List of abbreviations 5HT, serotonin; ADP, afterdepolarization; AHP, afterhyperpolarization; AP, action potential; ATP, adenosine triphosphate; BIC, Bayesian information criterion; CB, calbindin; ChR2, channelrhodopsin 2; DA, dopamine; DAT, dopamine transporter; GABA, γ-aminobutyric acid; Glu, glutamate; GMM, Gaussian mixture model; HFF, high-frequency firing; IPSCs, inhibitory postsynaptic currents; NAc, nucleus accumbens; PBP, parabrachial pigmented nucleus; PC, principal component; PCA, principal component analysis; PIF, parainterfascicular nucleus; PN, paranigral nucleus; PV, parvalbumin; Sst, somatostatin; TH, tyrosine hydroxylase; Vgat, vesicular GABA transporter; Vglut, vesicular glutamate transporter; VIP, vasoactive intestinal peptide; VTA, ventral tegmental area.