Whole-brain input mapping of the lateral versus medial anterodorsal bed nucleus of the stria terminalis in the mouse

The neurophysiological basis of stress and anxiety - comparing neuronal diversity in the bed nucleus of the stria terminalis (BNST) across species

“…Many connectivity studies regarding BNST ALG subnuclei were performed in the early 2,000 s in male rats and therefore much of the knowledge of the BNST connectivity therefore represents that of the male rat brain ( Dong et al, 2000 , 2001a , b ; Dong and Swanson, 2003 , 2004 , 2006 ; Dabrowska et al, 2013 ). More recently, connectivity studies have also been performed in mice and in macaques, using more modern viral tracing approaches ( deCampo and Fudge, 2013 ; Smith et al, 2016 ; Oler et al, 2017 ; Sun et al, 2023 ) and functional MRI (fMRI) or resting-state MRI (rsMRI) in humans ( Avery et al, 2014 ; Krüger et al, 2015 ; Hofmann and Straube, 2019 ). Many of these studies, as discussed below, have provided insight into differences in structural and functional connectivity between species.…”

“…The lateral hypothalamus, including the PVN, provides both glutamatergic and GABAergic input ( Berk and Finkelstein, 1982 ; Myers et al, 2014 ). This diverse pool of neurotransmitters together with released peptides shape BNST activity ( Canteras and Swanson, 1992 ; Dong et al, 2001b ; Sun et al, 2023 ). In addition, the BNST is also innervated by many neuromodulatory systems, such as dopamine, serotonin, and histamine amongst others ( Garcia-Garcia et al, 2018 ; Gyawali et al, 2023 ; Lin et al, 2023 ), which provide a further regulation of BNST activity, but these neuromodulators will not be discussed in detail in this Review.…”

“…A major and important dorsal BNST ALG reciprocal connection is with the cortex and in particular the PFC. Indeed, in rodents the prelimbic and anterior cingulate cortex provide the largest projections ( Dong et al, 2001a ; Vertes, 2004 ; Radley et al, 2009 ; Sun et al, 2023 ). The prelimbic cortex is thought to be involved in regulating fear expression amongst regulation of other emotions ( Sun et al, 2023 ), while the anterior cingulate cortex is more involved in regulating emotions and cognitive control ( Sun et al, 2023 ).…”

“…Indeed, in rodents the prelimbic and anterior cingulate cortex provide the largest projections ( Dong et al, 2001a ; Vertes, 2004 ; Radley et al, 2009 ; Sun et al, 2023 ). The prelimbic cortex is thought to be involved in regulating fear expression amongst regulation of other emotions ( Sun et al, 2023 ), while the anterior cingulate cortex is more involved in regulating emotions and cognitive control ( Sun et al, 2023 ). Other connections from PFC include those from infralimbic regions ( Reisiger et al, 2014 ; Glangetas et al, 2017 ).…”

“…Even though the BNST is larger (in proportion to brain size) and more developed in humans, rs/fMRI data seems to support a high level of conservation of inputs across species with humans exhibiting some new and stronger connections with some cortical regions ( Avery et al, 2014 ). An interesting connection seen in both rodent and human BNST is with the insular cortex ( Dong et al, 2001a ; Avery et al, 2014 ; Flook et al, 2020 ; Sun et al, 2023 ) which is thought to regulate BNST activity in relation to affective behavior ( Luchsinger et al, 2021 ; Glangetas, 2022 ). Interesting is this regard is the presence of so-called Von Economo or spindle cells which are found in high numbers in insular cortex and other anterior limbic areas in humans but not in many other primates or species, potentially providing a unique input and regulation of BNST in humans only ( Seeley et al, 2012 ; Table 1 ).…”