Neural circuit pathology driven by Shank3 mutation disrupts social behaviors

PL (Prelimbic area) MBA:972 projects to BLA (Basolateral amygdalar nucleus) MBA:295 · Mouse

Anterograde AAV8 encoding CreN-InteinN was placed in the PFC; after split-Cre reconstitution, tdTomato-labelled cell bodies appeared in prelimbic (and infralimbic) cortex and their labelled axons were followed to terminations in the basolateral amygdala.

Figures 1B, 1D-1G

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ILA (Infralimbic area) MBA:44 projects to BLA (Basolateral amygdalar nucleus) MBA:295 · Mouse

With retrograde AAV-InteinC-CreC delivered to the BLA, reconstituted-Cre reporter signal labelled somata in the infralimbic cortex as well as the prelimbic cortex, indicating infralimbic neurons projecting to the BLA.

Figure 1D; Results, 'Shank3 mutation alters the morphology of neurons in the PFC-BLA circuit'

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PL (Prelimbic area) MBA:972 synapses onto BLA (Basolateral amygdalar nucleus) MBA:295 · Mouse

When AAV9 rather than AAV8 was used to deliver CreN-InteinN to the PFC together with retrograde InteinC-CreC in the BLA, Cre-reporter somata appeared in the BLA as well as the PFC; the authors attribute this to anterograde transsynaptic spread of AAV9 to BLA recipient neurons, but the experiment was a specificity control rather than a test of synaptic contact.

Figures S2G-S2I; Results, 'Shank3 mutation in the PFC-BLA neural circuit'

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PL (Prelimbic area) MBA:972 projects to CP (Caudoputamen) MBA:672 · Mouse

Labelled axons of PFC neurons were visible within the medial striatum, but the authors describe these as fibres coursing through the striatum on their way to terminate in the BLA, so striatal innervation is not established.

Figures 1E and 1F

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PL (Prelimbic area) MBA:972 projects to BLA (Basolateral amygdalar nucleus) MBA:295 · Mouse

A retrograde AAV carrying InteinC-CreC injected into the BLA reconstituted Cre only in neurons whose axons reach the BLA, producing tdTomato-positive somata in the prelimbic cortex, showing that prelimbic neurons send axons to the BLA.

Figures 1B, 1D; Results, 'Shank3 mutation in the PFC-BLA neural circuit'

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) MBA:972 projects to BLA (Basolateral amygdalar nucleus) MBA:295 · Mouse

Cholera toxin subunit B conjugated to Alexa 488 injected into the BLA retrogradely labelled neurons in the PFC, which the authors compared against the split-Cre reconstitution labelling of the same pathway.

Figures S2J-S2R; STAR Methods, 'Surgery for conventional retrograde tracing'

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