A Transgenic Rat for Investigating the Anatomy and Function of Corticotrophin Releasing Factor Circuits

Rat central amygdala corticotropin-releasing hormone-expressing neurons nt-sexhekqxaa projects to SNc (Substantia nigra, compact part) UBERON:0001965 · Rat

Labelled CRF axons from the CeL were seen in the dorsolateral substantia nigra pars compacta, but the authors judged these to be most likely fibers of passage en route to the brainstem.

Fig. 5A-D

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Rat central amygdala corticotropin-releasing hormone-expressing neurons nt-sexhekqxaa projects to NTS (Nucleus of the solitary tract) UBERON:0009050 · Rat

A small projection from CeL CRF neurons reached the nucleus of the solitary tract along much of its rostrocaudal axis, with fibers ending in the caudal ventrolateral NTS near noradrenergic somata.

Fig. 4F-I

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Rat central amygdala corticotropin-releasing hormone-expressing neurons nt-sexhekqxaa functionally connects to CEA (central amygdaloid nucleus) UBERON:0002883 · Rat

CNO activation of hM3Dq in CeL CRF neurons also induced Fos in a subset of CeM neurons, an effect strongly attenuated by systemic CRF1 receptor blockade with R121919 while activation of the CRF neurons themselves was unaffected.

Fig. 7D-F

Made by an AI model reading the paper (claude-opus-5, extract@0.3.0); a second AI model (claude-opus-5) disagrees. “The CeM Fos result came from chemogenetic (hM3Dq/CNO) activation, not optogenetic circuit mapping.”

Rat central amygdala corticotropin-releasing hormone-expressing neurons nt-sexhekqxaa projects to LHA (Lateral hypothalamic area) UBERON:0002430 · Rat

Labelled CRF axons ran through the most lateral lateral hypothalamus within the nigrostriatal bundle along its full rostrocaudal extent; most appeared to be fibers of passage, with small branches extending medially into the LH, described as a minor projection.

Fig. 4D; Abstract

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Rat central amygdala corticotropin-releasing hormone-expressing neurons nt-sexhekqxaa projects to PB (Parabrachial nucleus) UBERON:0007634 · Rat

Cre-dependent AAV expressing mCherry (or ChR2-eYFP) in CeL CRF neurons produced the heaviest fiber labelling in the lateral and medial parabrachial nuclei, with fibers extending caudally within the medial PBN.

Fig. 3A-D; Results, 'Projections from CeL CRF neurons outside the CeA'

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Rat central amygdala corticotropin-releasing hormone-expressing neurons nt-sexhekqxaa projects to CP (Caudoputamen) UBERON:0005383 · Rat

Labelled CRF fibers in the dorsolateral BNST region also extended into the neighbouring dorsal striatum.

Results, 'Projections from CeL CRF neurons outside the CeA'; Fig. 4A

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Rat central amygdala corticotropin-releasing hormone-expressing neurons nt-sexhekqxaa projects to DR (Dorsal nucleus raphe) UBERON:0002043 · Rat

Labelled CeL CRF fibers projected dorsomedially into the caudal, tryptophan-hydroxylase-positive dorsal raphe nucleus.

Fig. 4E

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Rat central amygdala corticotropin-releasing hormone-expressing neurons nt-sexhekqxaa projects to SI (Substantia innominata) UBERON:0003017 · Rat

A sparser set of labelled fibers from CeL CRF neurons was found ventrolateral to the ventral BNST in the substantia innominata.

Fig. 4C

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Rat central amygdala corticotropin-releasing hormone-expressing neurons nt-sexhekqxaa projects to VTA (Ventral tegmental area) UBERON:0002691 · Rat

Close inspection revealed low-density collateral fibers from CeL CRF neurons within the rostral VTA, surrounding dopaminergic neurons; more caudally no VTA contact was seen.

Fig. 5E

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Rat central amygdala corticotropin-releasing hormone-expressing neurons nt-sexhekqxaa functionally connects to CEA (central amygdaloid nucleus) UBERON:0002883 · Rat

Optogenetic stimulation of CeL CRF terminals evoked picrotoxin-sensitive IPSCs in only 8 of 71 non-CRF CeM neurons, which were scattered across the CeM rather than clustered; IPSC amplitudes were comparable to those in CeL cells.

Fig. 6C,E,F; Results

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Rat central amygdala corticotropin-releasing hormone-expressing neurons nt-sexhekqxaa projects to PAG (Periaqueductal gray) UBERON:0003040 · Rat

Fibers from CeL CRF neurons coursed into the ventrolateral periaqueductal gray.

Fig. 4E

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Rat central amygdala corticotropin-releasing hormone-expressing neurons nt-sexhekqxaa projects to PALv (Pallidum, ventral region) UBERON:0002778 · Rat

Less dense labelled projections from CeL CRF neurons were detected in the ventral pallidum just ventrolateral to the ventral BNST.

Fig. 4C

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Rat central amygdala corticotropin-releasing hormone-expressing neurons nt-sexhekqxaa functionally connects to CEA (central amygdaloid nucleus) UBERON:0002883 · Rat

Blue-light stimulation of ChR2-expressing CeL CRF neurons evoked IPSCs in 8 of 18 recorded non-CRF CeL neurons; the evoked IPSCs were nearly abolished by picrotoxin, indicating GABAergic local inhibition.

Fig. 6C,E; Results

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Rat central amygdala corticotropin-releasing hormone-expressing neurons nt-sexhekqxaa projects to CEA (central amygdaloid nucleus) UBERON:0002883 · Rat

After Cre-dependent AAV injection into the CeA, only very few labelled fibers from CeL CRF neurons were found in the adjacent CeM, described as sparse mCherry/eYFP fiber labelling.

Figs. 1C, 6A; Results, 'Projections from CeL CRF neurons within the CeA'

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Rat central amygdala corticotropin-releasing hormone-expressing neurons nt-sexhekqxaa projects to BST (Bed nuclei of the stria terminalis) UBERON:0001880 · Rat

A dense bundle of labelled fibers from CeL CRF neurons was seen in the dorsolateral BNST (clustering around the oval nucleus) and especially in the ventral BNST subcommissural zone.

Fig. 4A,B

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Rat central amygdala corticotropin-releasing hormone-expressing neurons nt-sexhekqxaa projects to LC (Locus ceruleus) UBERON:0002148 · Rat

mCherry-labelled axons from CeL CRF neurons were among the largest and densest projections and reached the locus coeruleus, running orthogonally to the dendrites of tyrosine-hydroxylase-positive LC neurons.

Fig. 3B-D

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Rat central amygdala corticotropin-releasing hormone-expressing neurons nt-sexhekqxaa functionally connects to CEA (central amygdaloid nucleus) UBERON:0002883 · Rat

Chemogenetic activation of CeL CRF neurons with hM3Dq plus CNO induced Fos in non-CRF CeL neurons (absent with hM4Di or mCherry controls), and this Fos induction was reduced by about two-thirds by the CRF1 receptor antagonist R121919, indicating peptidergic excitation via local CRF release.

Fig. 7A-F

Made by an AI model reading the paper (claude-opus-5, extract@0.3.0); a second AI model (claude-opus-5) disagrees. “The CRF1-dependent Fos induction in CeL non-CRF neurons was obtained chemogenetically, not by optogenetic circuit mapping.”