Medial prefrontal cortex neurons integrate amygdala and hypothalamic oxytocin signals to mediate stress-induced social alterations

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

Optogenetic activation of ChrimsonR-expressing BLA axons in the prelimbic cortex raised the calcium activity of local vGAT-Cre-defined GABAergic neurons recorded by fibre photometry, indicating that glutamatergic BLA input drives prefrontal interneurons.

Supplementary Fig. 4a

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

Cre delivered from the BLA together with a Cre-dependent reporter in PL labelled most prelimbic neurons, with especially heavy labelling of superficial layers, indicating BLA innervation of PL cells that converges with PVN input on the same neurons.

Fig. 3f

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

After injecting an AAV expressing mCherry under the hSyn promoter into the basolateral amygdala of naive mice, abundant labelled axonal fibres were seen across the prelimbic prefrontal cortex.

Fig. 3d

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PVH (Paraventricular hypothalamic nucleus) MBA:38 projects to PL (Prelimbic area) MBA:972 · Mouse

An AAV expressing EYFP under the hSyn promoter injected into the paraventricular hypothalamic nucleus produced abundant green fibre labelling throughout the prelimbic cortex.

Fig. 3d

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PVH (Paraventricular hypothalamic nucleus) MBA:38 synapses onto PL (Prelimbic area) MBA:972 · Mouse

FLP delivered from the PVN with a FLP-dependent mCherry reporter in PL labelled prelimbic neurons, the majority of which were also labelled by the BLA-derived Cre reporter, showing convergent PVN innervation of individual PL neurons.

Fig. 3f

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

Silencing NpHR-expressing BLA axons within the prelimbic cortex with amber light increased the calcium transient rate of CaMKII-positive prefrontal neurons imaged by miniscope, both in the home cage and during social testing, showing that BLA input exerts a net suppressive influence on prefrontal excitatory neurons.

Fig. 4d, f; Supplementary Fig. 4b

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PVH (Paraventricular hypothalamic nucleus) MBA:38 projects to PL (Prelimbic area) MBA:972 · Mouse

Retrograde AAV-hSyn-EGFP injected into the prelimbic cortex labelled neurons in the paraventricular hypothalamic nucleus; retrograde Cre viruses (hSyn-Cre or OXT-Cre) delivered to PL also drove Cre-dependent expression in PVN neurons, including oxytocinergic ones.

Fig. 3e; Fig. 5a, g

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

A retrograde AAV (AAV-retro-hSyn-EGFP) injected into the prelimbic cortex labelled cell bodies in the basolateral amygdala; a retrograde CaMKII-GCaMP virus in PL likewise labelled BLA projection neurons for photometry.

Fig. 3e; Fig. 4a

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PVH (Paraventricular hypothalamic nucleus) MBA:38 functionally connects to PL (Prelimbic area) MBA:972 · Mouse

Optogenetic inhibition of oxytocinergic PVN axon terminals in the prelimbic cortex raised the calcium transient rate of prefrontal excitatory neurons in acutely and chronically stressed mice (but not in unstressed mice), indicating a state-dependent suppressive action of PVN oxytocin input on prefrontal pyramidal activity.

Fig. 6c, d

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