Species‐specific diversity in the anatomical and physiological organisation of the BNST ‐ VTA pathway

Abstract The anteromedial part of the bed nucleus of the stria terminalis (am BNST ) is a limbic structure innervating the ventral tegmental area ( VTA ) that is remarkably constant across species. The am BNST modulates fear and anxiety, and activation of VTA dopamine ( DA ) neurons by am BNST afferents seems to be the way by which stress controls motivational states associated with reward or aversion. Because fear learning and anxiety states can be expressed differently between rats and mice, we compared the functional connectivity between am BNST and the VTA ‐ DA neurons in both species using consistent methodological approaches. Using a combination of in vivo electrophysiological, neuroanatomical tracing and laser capture approaches we explored the BNST influences on VTA ‐ DA neuron activity. First, we characterised in rats the molecular phenotype of the am BNST neurons projecting to the VTA . We found that this projection is complex, including both GABA ergic and glutamatergic neurons. Then, VTA injections of a conventional retrograde tracer, the β‐sub‐unit of the cholera toxin ( CTB ), revealed a stronger BNST ‐ VTA projection in mice than in rats. Finally, electrical stimulations of the BNST during VTA ‐ DA neuron recording demonstrated a more potent excitatory influence of the am BNST on VTA ‐ DA neuron activity in rats than in mice. These data illustrate anatomically, but also functionally, a significant difference between rats and mice in the am BNST ‐ VTA pathway. More generally, together with previous findings, our research highlights the importance of species differences for the interpretation and the generalisation of research data.