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. 2022 May 17;530(13):2254–2285. doi: 10.1002/cne.25331

TABLE 3.

Neural circuits underlying learned (conditioned) responses to threat stimuli

LPO and LHA outputs LPO and LHA inputs
Predator threat LPO LHAa Regions LPO LHAa
Predatory contextual cues → Septo‐hippocampal system (SHS) 7 7 SHS 7 7
Amygdala ↓ 0 0 LA 1 1
3 2 BMAp 2 2
Predator‐responsive hypothalamic circuit ↓ 4 3 AHN 2 2
1 0 VMHdm 3 4
2 4 PMd (vl) 0 1
Conditioned behavioral responses to predator threat ← Brainstem 2 2 PAGdl 1 1
LPO and LHA outputs LPO and LHA inputs
Social defeat LPO LHAa Regions LPO LHAa
Contextual cues → Septo‐hippocampal system (SHS) 7 7 SHS 7 7
Odor cues from an aggressive conspecific → Amygdala ↓ 3 3 MEAad 4 3
2 2 MEApd 1 1
Conspecific‐responsive hypothalamic circuit ↓ 6 4 LHAjd 2 3
6 6 LHAs 1 3
2 4 PMd (dm) 0 1
4 3 MPO 4 4
1 3 VMHvl 3 3
2 2 PMv 2 4
Conditioned behavioral responses to social threat ← Brainstem 1 2 PAGdm 2 1
LPO and LHA outputs LPO and LHA inputs
Painful stimulus LPO LHAa Regions LPO LHAa
Contextual cues (previously paired with painful stimuli) → Septo‐hippocampal system (SHS) ↓ 7 7 SHS 7 7
↑ Amygdala ↓ 0 0 LA 1 1
0 0 BLA 0 0
2 1 CEA 1 2
Conditioned behavioral responses to painful stimulus ← Brainstem 4 2 PAGvl 1 2

Note: Comparison of LPO and LHAa connections with other gray matter regions and circuits identified in three models of learned (conditioned) defensive behavioral responses relating to three different categories of threat stimuli: predator, social, and painful (Canteras & Graeff, 2014). For each stimulus category, three separate columns associated with the model list (from left to right): (1) stimuli and responses, (2) major brain divisions involved, and (3) gray matter regions involved. Arrows in the first two columns indicate the direction of information flow. Two columns on either side of the regions column list LPO and LHAa output and input connections with the associated regions. LPO and LHAa connection weights are highest binned values following a 1–7/weakest‐strongest color scale (see Supporting Information 1 and 2, and text for further details). Note that for the dorsal premammillary nucleus (PMd), a distinction is made in the behavioral model between ventrolateral and dorsomedial subdivisions; however, no clear distinction in this regard was apparent in LPO and LHAa PMd connections, therefore, the same PMd connection value was applied to both. Additionally, for divisions identified in the behavioral model that contain more than one gray matter region (that are listed in the regions column), the highest LPO and LHAa connection weight across all constituent regions was selected, which applies to the following divisions: septohippocampal system (SHS) that includes the septal nuclei and the hippocampal formation; anterior hypothalamic nucleus (AHN), dorsomedial hypothalamic nucleus (DMH), and central amygdalar nucleus (CEA). Additional abbreviations: BLA, basolateral amygdalar nucleus; BMAp, basomedial amygdalar nucleus posterior part; LA, lateral amygdalar nucleus; LHAjd, lateral hypothalamic area juxtadorsomedial region; LHAs, lateral hypothalamic area suprafornical region; MEAad, medial amygdalar nucleus anterodorsal part; MEApd, medial amygdalar nucleus posterodorsal part; MEApv, medial amygdalar nucleus posteroventral part; MPO, medial preoptic area; PAGdl, periaqueductal gray dorsolateral column; PAGdm, periaqueductal gray dorsomedial column; PAGl, periaqueductal gray lateral column; PAGvl, periaqueductal gray ventrolateral column; PMv, ventral premammillary nucleus; VMHdm, ventromedial hypothalamic nucleus dorsomedial part; VMHvl, ventromedial hypothalamic nucleus ventrolateral part.