Drug-induced changes in connectivity to midbrain dopamine cells revealed by rabies monosynaptic tracing

LH (Lateral habenula) MBA:186 synapses onto VTA (Ventral tegmental area) MBA:749 · Mouse

Lateral habenula neurons were rabies-labelled from vGluT2-Cre-defined glutamatergic VTA neurons and contributed strongly to the component on which glutamatergic brains were enriched.

Fig. 1C, Fig. 1G

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VTA (Ventral tegmental area) MBA:749 projects to BLA (Basolateral amygdalar nucleus) MBA:295 · Mouse

Retrograde CAV2-FLEx-Flp injected into the basolateral amygdala region labelled a subset of VTA dopamine neurons, which were then used as starter cells for input mapping, demonstrating a VTA dopamine projection to the amygdala.

Fig. 7M–P; Methods (cTRIO, amygdala coordinates AP −1.43, ML 2.5, DV −4.5)

Made by an AI model reading the paper (claude-opus-5, extract@0.3.0); a second AI model (claude-opus-5) is unsure. “The paper only designates the retrograde target as "Amygdala", so restriction to the basolateral nucleus cannot be confirmed.”

LSX (Lateral septal complex) MBA:275 synapses onto VTA (Ventral tegmental area) MBA:749 · Mouse

Septal neurons were labelled transsynaptically from VTA dopamine starter cells; septal labelling was among the inputs reduced in mice treated with a single dose of an addictive drug.

Fig. 1C, Fig. 3G

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DR (Dorsal nucleus raphe) MBA:872 synapses onto VTA (Ventral tegmental area) MBA:749 · Mouse

Dorsal raphe neurons were rabies-labelled from VTA dopamine starter cells and contributed to the component enriched in drug-treated brains.

Fig. 1C, Fig. 5E, Fig. 5K

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GPe (Globus pallidus, external segment) MBA:1022 synapses onto VTA (Ventral tegmental area) MBA:749 · Mouse

External globus pallidus neurons were labelled as presynaptic inputs to GABAergic VTA neurons in GAD2-Cre mice, with relative enrichment over dopamine cells.

Fig. 1B–C, Fig. 1G

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BST (Bed nuclei of the stria terminalis) MBA:351 synapses onto VTA (Ventral tegmental area) MBA:749 · Mouse

Rabies-labelled input neurons were seen in the bed nucleus of the stria terminalis after tracing from VTA dopamine neurons, and BNST labelling loaded positively on the component separating drug-treated from control brains.

Fig. 1B–C, Fig. 5D–E

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Isocortex MBA:315 synapses onto VTA (Ventral tegmental area) MBA:749 · Mouse

Monosynaptic rabies tracing from Cre-defined dopamine neurons in the VTA of DAT-Cre mice labelled presynaptic neurons in anterior cortical areas, one of the 22 quantified input regions.

Fig. 1C, Fig. 5E

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PALv (Pallidum, ventral region) MBA:835 synapses onto VTA (Ventral tegmental area) MBA:749 · Mouse

The ventral pallidum contained rabies-labelled presynaptic neurons after tracing from dopamine neurons in the VTA of DAT-Cre mice.

Fig. 1C, Fig. 5E

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CEA (Central amygdalar nucleus) MBA:536 synapses onto VTA (Ventral tegmental area) MBA:749 · Mouse

Central amygdala neurons were rabies-labelled from GABAergic VTA starter cells and were relatively enriched onto this population compared with dopamine cells.

Fig. 1C, Fig. 1G

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LH (Lateral habenula) MBA:186 synapses onto VTA (Ventral tegmental area) MBA:749 · Mouse

Lateral habenula neurons were rabies-labelled from VTA dopamine starter cells in DAT-Cre mice.

Fig. 1C, Fig. 5E

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CEA (Central amygdalar nucleus) MBA:536 synapses onto VTA (Ventral tegmental area) MBA:749 · Mouse

The central amygdala contained rabies-labelled neurons presynaptic to VTA dopamine cells, contributing positively to the principal component that distinguished drug-treated brains.

Fig. 1C, Fig. 5E, Fig. 5K

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CBN (Cerebellar nuclei) MBA:519 synapses onto VTA (Ventral tegmental area) MBA:749 · Mouse

Representative images and quantification show rabies-labelled deep cerebellar nuclei neurons after tracing from GABAergic VTA cells in GAD2-Cre mice.

Fig. 1B–C

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LDT (Laterodorsal tegmental nucleus) MBA:162 synapses onto VTA (Ventral tegmental area) MBA:749 · Mouse

The laterodorsal tegmental nucleus was one of the 22 quantified regions containing rabies-labelled inputs to VTA dopamine neurons.

Fig. 1C, Fig. 5E

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ZI (Zona incerta) MBA:797 synapses onto VTA (Ventral tegmental area) MBA:749 · Mouse

Zona incerta neurons were labelled as inputs to vGluT2-Cre glutamatergic VTA cells.

Fig. 1C, Fig. 1G

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ZI (Zona incerta) MBA:797 synapses onto VTA (Ventral tegmental area) MBA:749 · Mouse

Zona incerta neurons were labelled as monosynaptic inputs to VTA dopamine cells in DAT-Cre mice.

Fig. 1C, Fig. 5E, Fig. 5K

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GPi (Globus pallidus, internal segment) MBA:1031 synapses onto VTA (Ventral tegmental area) MBA:749 · Mouse

Entopeduncular nucleus neurons were rabies-labelled from glutamatergic VTA starter cells in vGluT2-Cre mice.

Fig. 1C, Fig. 1G

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VTA (Ventral tegmental area) MBA:749 projects to ACB (Nucleus accumbens) MBA:56 · Mouse

Retrograde CAV2-FLEx-Flp injected into the lateral or medial shell of the nucleus accumbens recombined in Cre-expressing VTA dopamine neurons, allowing input tracing from VTADA→NAcLat and VTADA→NAcMed populations and showing that VTA dopamine cells project to these accumbens subregions.

Fig. 7G–L, Fig. 7—figure supplement 2; Methods (cTRIO)

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MH (Medial habenula) MBA:483 synapses onto VTA (Ventral tegmental area) MBA:749 · Mouse

Medial habenula neurons were labelled as presynaptic inputs to glutamatergic VTA cells, consistent with these cells lying in the medial VTA.

Fig. 1C, Fig. 1G

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PB (Parabrachial nucleus) MBA:867 synapses onto VTA (Ventral tegmental area) MBA:749 · Mouse

Parabrachial nucleus neurons were labelled as inputs to VTA dopamine cells, and this input was increased after a single exposure to an addictive drug.

Fig. 5D–E, Fig. 5K, Fig. 3G

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BST (Bed nuclei of the stria terminalis) MBA:351 synapses onto VTA (Ventral tegmental area) MBA:749 · Mouse

Rabies tracing from GAD2-Cre-defined GABAergic VTA neurons labelled BNST neurons, and BNST input labelling was relatively enriched onto GABAergic compared with dopaminergic VTA cells.

Fig. 1B–C, Fig. 1G

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HY (Hypothalamus) MBA:1097 synapses onto VTA (Ventral tegmental area) MBA:749 · Mouse

Rabies tracing from VTA dopamine neurons labelled cells in the preoptic area, counted as one of the 22 input regions.

Fig. 1C, Fig. 5E

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GPe (Globus pallidus, external segment) MBA:1022 synapses onto VTA (Ventral tegmental area) MBA:749 · Mouse

Rabies tracing from VTA dopamine neurons labelled external globus pallidus neurons; the proportion of GPe input cells was significantly higher after a single injection of an addictive drug than in controls (p = 0.0036).

Fig. 1B–C, Fig. 3G, Fig. 5D–E

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MH (Medial habenula) MBA:483 synapses onto VTA (Ventral tegmental area) MBA:749 · Mouse

Medial habenula neurons were labelled as inputs to VTA dopamine cells; this input was reduced in brains from mice given a single addictive drug exposure.

Fig. 1C, Fig. 3G, Fig. 5K

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

CBN (Cerebellar nuclei) MBA:519 synapses onto VTA (Ventral tegmental area) MBA:749 · Mouse

Deep cerebellar nuclei neurons were rabies-labelled after tracing from glutamatergic VTA cells, contributing to the component on which vGluT2-Cre brains scored highest.

Fig. 1B–C, Fig. 1G

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GPi (Globus pallidus, internal segment) MBA:1031 synapses onto VTA (Ventral tegmental area) MBA:749 · Mouse

The entopeduncular nucleus provided rabies-labelled inputs to VTA dopamine neurons, with labelling increased after a single exposure to an addictive drug.

Fig. 1C, Fig. 3G, Fig. 5K

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LHA (Lateral hypothalamic area) MBA:194 synapses onto VTA (Ventral tegmental area) MBA:749 · Mouse

Lateral hypothalamic neurons were rabies-labelled from VTA dopamine cells, and their labelling increased after a single injection of an addictive drug.

Fig. 1C, Fig. 3G, Fig. 5K

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ACB (Nucleus accumbens) MBA:56 synapses onto VTA (Ventral tegmental area) MBA:749 · Mouse

Rabies tracing from VTA dopamine neurons labelled input cells in the medial shell, lateral shell and core of the nucleus accumbens; accumbens labelling (medial shell and core) was reduced after a single dose of an addictive drug, and CRISPRi knockdown of Cacna1e in the lateral shell lowered the number of rabies-labelled accumbens inputs to VTA dopamine cells.

Fig. 1C, Fig. 5D–E, Fig. 10F

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sAMY (Striatum-like amygdalar nuclei) MBA:278 synapses onto VTA (Ventral tegmental area) MBA:749 · Mouse

Extended amygdalar areas contained rabies-labelled neurons presynaptic to VTA dopamine cells, and this input was increased in mice given a single injection of an addictive drug.

Fig. 3G, Fig. 5E, Fig. 5K

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Isocortex MBA:315 synapses onto VTA (Ventral tegmental area) MBA:749 · Mouse

Cortical neurons were labelled as inputs to glutamatergic VTA cells in vGluT2-Cre mice.

Fig. 1C, Fig. 1G

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VTA (Ventral tegmental area) MBA:749 projects to PL (Prelimbic area) MBA:972 · Mouse

Retrograde CAV2-FLEx-Flp delivered to medial prefrontal cortex recombined in Cre-positive VTA dopamine neurons, defining a VTADA→mPFC population and showing that VTA dopamine cells project to medial prefrontal cortex.

Fig. 7—figure supplement 2E–H; Methods (cTRIO, mPFC injections)

Made by an AI model reading the paper (claude-opus-5, extract@0.3.0); a second AI model (claude-opus-5) is unsure. “The paper specifies only mPFC as the retrograde injection site, so the prelimbic-specific assignment is not established.”

PVH (Paraventricular hypothalamic nucleus) MBA:38 synapses onto VTA (Ventral tegmental area) MBA:749 · Mouse

Neurons in the paraventricular hypothalamic nucleus were labelled by monosynaptic rabies tracing from VTA dopamine cells, and this input was more strongly labelled in ketamine/xylazine-anesthetized mice.

Fig. 1C, Fig. 5E, Fig. 7B

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CP (Caudoputamen) MBA:672 synapses onto VTA (Ventral tegmental area) MBA:749 · Mouse

Rabies-labelled inputs to VTA dopamine neurons were found in the dorsal striatum; the share of dorsal striatal input cells was significantly lower in mice given a single injection of an addictive drug than in controls (p = 0.0051).

Fig. 1C, Fig. 3G

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CBN (Cerebellar nuclei) MBA:519 synapses onto VTA (Ventral tegmental area) MBA:749 · Mouse

Deep cerebellar nuclei neurons were rabies-labelled after tracing from dopamine neurons in the VTA of DAT-Cre mice.

Fig. 1B–C, Fig. 5E

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