Nucleus accumbens D1/D2 circuits control opioid withdrawal symptoms in mice

BLA (Basolateral amygdalar nucleus) MBA:295 projects to ACB (Nucleus accumbens) MBA:56 · Mouse

Virally expressed fluorophores (Chronos-eGFP, Cre-dependent constructs) injected into the basolateral amygdala labelled fibres reaching the nucleus accumbens.

Fig. 6G; Fig. 7A

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BLA (Basolateral amygdalar nucleus) MBA:295 functionally connects to ACB (Nucleus accumbens) MBA:56 · Mouse

Optical stimulation of Chronos/ChR2-expressing BLA terminals also elicited excitatory postsynaptic currents in accumbens D2 medium spiny neurons (which lacked the D1 fluorescent tag), although this input showed no AMPA/NMDA change and no long-term potentiation.

Fig. 4C; Fig. 7A, B

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BLA (Basolateral amygdalar nucleus) MBA:295 projects to ACB (Nucleus accumbens) MBA:56 · Mouse

Fluorogold injected into the nucleus accumbens retrogradely labelled neurons in the basolateral amygdala, which were then co-stained for c-Fos and for KOR mRNA, showing that BLA cells send axons to NAc.

Fig. 3D-F, H; Fig. 6A-C

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PVT (Paraventricular nucleus of the thalamus) MBA:149 functionally connects to ACB (Nucleus accumbens) MBA:56 · Mouse

Light stimulation of ChR2-expressing PVT axons in accumbens slices evoked AMPAR/NMDAR excitatory currents in D2-eGFP medium spiny neurons; the AMPA/NMDA ratio of this input was elevated after morphine withdrawal and 1 Hz optical stimulation produced a lasting depression of the response (to about 31.5% of baseline, n = 16 neurons from 4 mice).

Fig. 4A, B; Fig. 5A-C

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PVT (Paraventricular nucleus of the thalamus) MBA:149 functionally connects to ACB (Nucleus accumbens) MBA:56 · Mouse

Optically evoked excitatory postsynaptic currents from PVT terminals were also recorded in accumbens D1 medium spiny neurons; these responses were unchanged by 1 Hz optical low-frequency stimulation (about 104% of baseline, n = 9 neurons from 3 mice) and their AMPA/NMDA ratio was unaltered by morphine withdrawal.

Fig. 4B; Fig. 5C

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PVT (Paraventricular nucleus of the thalamus) MBA:149 projects to ACB (Nucleus accumbens) MBA:56 · Mouse

After AAV-CaMK2-ChR2 injection into the paraventricular thalamus, labelled axon terminals were visible in the nucleus accumbens of D2-eGFP mice.

Fig. 5B

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BLA (Basolateral amygdalar nucleus) MBA:295 functionally connects to ACB (Nucleus accumbens) MBA:56 · Mouse

Light activation of ChR2- or Chronos-expressing BLA axons in accumbens slices evoked AMPAR- and NMDAR-mediated excitatory postsynaptic currents in identified D1 medium spiny neurons; the AMPA/NMDA ratio of this input was reduced in depressive-like morphine-withdrawn mice, and the input could be potentiated by paired optogenetic high-frequency stimulation.

Fig. 4A, C; Fig. 7A-C

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PVT (Paraventricular nucleus of the thalamus) MBA:149 projects to ACB (Nucleus accumbens) MBA:56 · Mouse

Fluorogold deposited in the nucleus accumbens labelled neurons in the paraventricular thalamic nucleus, which were co-labelled for c-Fos and probed for KOR mRNA, indicating a PVT projection to NAc.

Fig. 3D-G; Fig. 6A-C

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