Chemogenetic inhibition of prefrontal cortex inputs to dorsal raphe reduces anxiety behaviors in male rat model of fetal alcohol spectrum disorder

DR (Dorsal nucleus raphe) UBERON:0002043 projects to CEA (central amygdaloid nucleus) UBERON:0002883 · Rat

Retrograde AAV-CAG-tdTomato injected into the central amygdala labelled dorsal raphe neurons, distributed across DRN subdivisions rostrally and along the ventromedial midline caudally; about 80% of these labelled DRN neurons were Tph2-positive and roughly 40% were nNOS-positive.

Fig. 4A–D; Fig. 6A–C

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LH (Lateral habenula) UBERON:0001941 functionally connects to DR (Dorsal nucleus raphe) UBERON:0002043 · Rat

ChR2 expression in lateral habenula allowed light activation of LHb fibres in DRN, which evoked excitatory currents in mPFC-projecting 5-HT neurons that were blocked by TTX and rescued by 4-AP, showing a direct monosynaptic glutamatergic LHb input. Amplitudes (~47 pA in controls) and paired-pulse ratios were unchanged by prenatal ethanol, and the NO donor SNAP did not modulate these currents.

Fig. 2E–H; Fig. 3F–G

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PL (Prelimbic area) UBERON:8440032 functionally connects to DR (Dorsal nucleus raphe) UBERON:0002043 · Rat

With ChR2 expressed in mPFC and DRN neurons retrogradely labelled from mPFC, light stimulation of mPFC axons within DRN evoked excitatory postsynaptic currents in mPFC-projecting 5-HT neurons (recorded with picrotoxin present); these currents were abolished by TTX and restored by 4-AP, indicating a direct monosynaptic glutamatergic input. Amplitudes averaged about 47 pA in controls and were larger in prenatally ethanol-exposed rats, which also showed a reduced paired-pulse ratio; the NO donor SNAP potentiated these currents in controls.

Fig. 2A–D; Fig. 3D–E

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PL (Prelimbic area) UBERON:8440032 projects to DR (Dorsal nucleus raphe) UBERON:0002043 · Rat

Retrograde rAAV-pgk-Cre injected into the dorsal raphe together with a Cre-dependent hM4Di-mCherry virus in medial prefrontal cortex produced mCherry-labelled pyramidal neurons in mPFC, identifying an mPFC population that projects to DRN.

Fig. 7A–B

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LH (Lateral habenula) UBERON:0001941 functionally connects to DR (Dorsal nucleus raphe) UBERON:0002043 · Rat

Photostimulation of ChR2-expressing lateral habenula fibres in DRN evoked monosynaptic excitatory currents in CeA-projecting 5-HT neurons; amplitudes (about 51 pA in controls) did not differ significantly from prenatal-ethanol rats, but the paired-pulse ratio was strongly reduced after prenatal ethanol, and the NO donor SNAP potentiated these currents only in controls.

Fig. 5E–H; Fig. 6F–G

Made by an AI model reading the paper (claude-opus-5, extract@0.3.0); a second AI model (claude-opus-5) agrees.

PL (Prelimbic area) UBERON:8440032 functionally connects to DR (Dorsal nucleus raphe) UBERON:0002043 · Rat

In slices with ChR2 in mPFC and DRN neurons retrogradely labelled from the central amygdala, photostimulation of mPFC fibres evoked monosynaptic excitatory currents (TTX-sensitive, rescued by 4-AP) in CeA-projecting 5-HT neurons, with mean amplitude near 49 pA in both control and prenatal-ethanol rats; paired-pulse ratio was lower after prenatal ethanol and SNAP enhanced the currents in controls.

Fig. 5A–D; Fig. 6D–E

Made by an AI model reading the paper (claude-opus-5, extract@0.3.0); a second AI model (claude-opus-5) agrees.

DR (Dorsal nucleus raphe) UBERON:0002043 projects to PL (Prelimbic area) UBERON:8440032 · Rat

Bilateral injection of retrograde AAV-CAG-tdTomato into medial prefrontal cortex labelled neurons in the dorsal raphe, clustered mainly in the interfascicular/ventromedial DRN, showing that DRN neurons project to mPFC. Most of these retrogradely labelled cells were Tph2-positive (serotonergic) and more than 73% were nNOS-positive.

Fig. 1A–D; Fig. 3A–C

Made by an AI model reading the paper (claude-opus-5, extract@0.3.0); a second AI model (claude-opus-5) agrees.