Identification of a prefrontal cortex-to-amygdala pathway for chronic stress-induced anxiety

PL (Prelimbic area) MBA:972 projects to CEA (Central amygdalar nucleus) MBA:536 · Mouse

No ChR2-eGFP-labelled dorsomedial prefrontal fibres were found in the central amygdala, in contrast to the dense labelling in BLA.

Fig. 1b; Results, first section

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PL (Prelimbic area) MBA:972 functionally connects to BLA glutamatergic principal neurons nt-wprma5fcrr · Mouse

Light activation of ChR2-expressing dorsomedial prefrontal axons in slices produced biphasic currents in basolateral amygdala principal neurons: a short-latency monosynaptic EPSC (about 4 ms onset, abolished by TTX and partly restored with 4-AP) followed by a longer-latency disynaptic IPSC that was blocked by glutamate receptor antagonists or by picrotoxin, indicating feedforward recruitment of local interneurons.

Fig. 1d–h; Supplementary Fig. 1a–f

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

After injecting a CaMKII-driven AAV expressing ChR2-eGFP into dorsomedial prefrontal cortex, heavily labelled axonal fibres were seen in the basolateral amygdala.

Fig. 1b; Results, first section

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

Red fluorescent retrobeads deposited in the dorsomedial prefrontal cortex retrogradely labelled a subset of principal neurons in the basolateral amygdala, identifying BLA cells that project back to dmPFC.

Fig. 2a, b

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BLA (Basolateral amygdalar nucleus) MBA:295 projects to HIP (Hippocampal region) MBA:1080 · Mouse

Retrobeads injected into the ventral hippocampus labelled a subset of basolateral amygdala principal neurons, identifying BLA cells that send axons to vHPC.

Supplementary Fig. 3; Methods, stereotaxic surgery

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PL (Prelimbic area) MBA:972 projects to LA (Lateral amygdalar nucleus) MBA:131 · Mouse

ChR2-eGFP-labelled fibres from the dorsomedial prefrontal injection were not detected in the lateral amygdaloid nucleus.

Fig. 1b; Results, first section

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

Retrobeads co-injected with the viral vector into ventral medial prefrontal cortex labelled basolateral amygdala principal neurons, defining a vmPFC-projecting BLA population.

Supplementary Fig. 2; Methods, stereotaxic surgery

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

AAV-ChR2-eGFP injected in ventral medial prefrontal cortex produced labelled axon terminals within the basolateral amygdala.

Fig. 1i, j

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HIP (Hippocampal region) MBA:1080 functionally connects to BLA glutamatergic principal neurons nt-wprma5fcrr · Mouse

Photostimulation of ventral hippocampal terminals evoked biphasic excitatory-then-inhibitory currents in basolateral amygdala principal neurons; amplitudes and their ratio were unaffected by chronic restraint stress.

Fig. 1r–v

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HIP (Hippocampal region) MBA:1080 projects to BLA (Basolateral amygdalar nucleus) MBA:295 · Mouse

AAV-ChR2-eGFP injected into the ventral hippocampus labelled axonal fibres in the basolateral amygdala.

Fig. 1p, q

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ILA (Infralimbic area) MBA:44 functionally connects to BLA glutamatergic principal neurons nt-wprma5fcrr · Mouse

Optogenetic stimulation of ventral medial prefrontal fibres in slices evoked biphasic EPSC/IPSC responses in basolateral amygdala principal neurons held at -30 mV, and these responses were unchanged by chronic restraint stress.

Fig. 1k–o

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