RT Journal Article SR Electronic T1 Three Types of Neurochemical Projection from the Bed Nucleus of the Stria Terminalis to the Ventral Tegmental Area in Adult Mice JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 18035 OP 18046 DO 10.1523/JNEUROSCI.4057-12.2012 VO 32 IS 50 A1 Takehiro Kudo A1 Motokazu Uchigashima A1 Taisuke Miyazaki A1 Kohtarou Konno A1 Miwako Yamasaki A1 Yuchio Yanagawa A1 Masabumi Minami A1 Masahiko Watanabe YR 2012 UL http://www.jneurosci.org/content/32/50/18035.abstract AB Dopaminergic (DAergic) neurons in the ventral tegmental area (VTA) play crucial roles in motivational control of behaviors, and their activity is regulated directly or indirectly via GABAergic neurons by extrinsic afferents from various sources, including the bed nucleus of the stria terminalis (BST). Here, the neurochemical composition of VTA-projecting BST neurons and their outputs to the VTA were studied in adult mouse brains. By combining retrograde tracing with fluorescence in situ hybridization for 67 kDa glutamate decarboxylase (GAD67) and vesicular glutamate transporters (VGluTs), VTA-targeting BST neurons were classified into GAD67-positive (GAD67+)/VGluT3-negative (VGluT3−), GAD67+/VGluT3+, and VGluT2+ neurons, of which GAD67+/VGluT3− neurons constituted the majority (∼90%) of VTA-projecting BST neurons. GABAergic efferents from the BST formed symmetrical synapses on VTA neurons, which were mostly GABAergic neurons, and expressed GABAA receptor α1 subunit on their synaptic and extrasynaptic membranes. In the VTA, VGluT3 was detected in terminals expressing vesicular inhibitory amino acid transporter (VIAAT), plasmalemmal serotonin transporter, or neither. Of these, VIAAT+/VGluT3+ terminals, which should include those from GAD67+/VGluT3+ BST neurons, formed symmetrical synapses. When single axons from VGluT3+ BST neurons were examined, almost all terminals were labeled for VIAAT, whereas VGluT3 was often absent from terminals with high VIAAT loads. VGluT2+ terminals in the VTA exclusively formed asymmetrical synapses, which expressed AMPA receptors on postsynaptic membrane. Therefore, the major mode of the BST–VTA projection is GABAergic, and its activation is predicted to disinhibit VTA DAergic neurons. VGluT2+ and VGluT3+ BST neurons further supply additional projections, which may principally convey excitatory or inhibitory inputs, respectively, to the VTA.