Control of parallel hippocampal output pathways by amygdalar long-range inhibition

BLA (Basolateral amygdalar nucleus) MBA:295 projects to CA1 (Field CA1) MBA:382 · Mouse

Immunostaining for somatostatin on sections containing amygdalar neurons retrogradely labelled from ventral hippocampus showed that a proportion of these projection neurons were somatostatin-immunopositive.

Fig. 2—figure supplement 2

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BLA (Basolateral amygdalar nucleus) MBA:295 functionally connects to CA1 (Field CA1) MBA:382 · Mouse

Activating ChR2 confined to GABAergic BA neurons evoked inhibitory (inward, high-chloride internal) currents in roughly half of the identified vH interneurons recorded, showing that the long-range inhibitory projection also targets local interneurons.

Fig. 5C,D

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BLA (Basolateral amygdalar nucleus) MBA:295 functionally connects to CA1 (Field CA1) MBA:382 · Mouse

Paired recordings of NAc-projecting and BA-projecting vH neurons in the same field of view showed that light-evoked excitatory BA input was on average equal onto the two populations (9 pairs with pan-neuronal ChR2; 10 pairs with CaMKii ChR2).

Fig. 4A-C; Fig. 5L-N

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BLA (Basolateral amygdalar nucleus) MBA:295 functionally connects to CA1 (Field CA1) MBA:382 · Mouse

In 7 pairs of PFC-projecting and BA-projecting vH neurons, activation of GABAergic BA axons produced essentially no inhibitory current in the PFC-projecting cells.

Fig. 4J-L

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BLA (Basolateral amygdalar nucleus) MBA:295 projects to CA1 (Field CA1) MBA:382 · Mouse

A cre-dependent smFP tracer injected into basal amygdala of vGAT-cre mice labelled inhibitory neurons whose axons innervated the CA1/subiculum border of ventral hippocampus.

Fig. 2—figure supplement 3B

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COA (Cortical amygdalar area) MBA:631 projects to CA1 (Field CA1) MBA:382 · Mouse

Cortical amygdalar areas contained retrogradely labelled cells after cholera toxin B injection into ventral hippocampus.

Fig. 1B-D

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BLA (Basolateral amygdalar nucleus) MBA:295 projects to CA1 (Field CA1) MBA:382 · Mouse

A virus expressing GFP under the CaMKii promoter injected in basal amygdala labelled excitatory cell bodies there and axons innervating distal CA1 of the ventral hippocampus.

Fig. 2—figure supplement 3A

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BLA (Basolateral amygdalar nucleus) MBA:295 functionally connects to CA1 (Field CA1) MBA:382 · Mouse

Light activation of basal amygdala axons expressing ChR2 under the synapsin promoter evoked short-latency currents at -70 mV in about 40% of recorded ventral hippocampal pyramidal neurons, and these currents were abolished by the AMPA receptor blocker NBQX (n = 9 neurons).

Fig. 2B,C

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CA1 (Field CA1) MBA:382 projects to ACB (Nucleus accumbens) MBA:56 · Mouse

Cholera toxin B injected into nucleus accumbens retrogradely labelled a distinct set of neurons in the ventral CA1/subiculum border.

Fig. 3A-D

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LA (Lateral amygdalar nucleus) MBA:131 projects to CA1 (Field CA1) MBA:382 · Mouse

Whole-brain registration of retrogradely labelled cells after vH cholera toxin B injection included a proportion of labelled neurons in the lateral amygdalar nucleus.

Fig. 1C,D

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BLA (Basolateral amygdalar nucleus) MBA:295 functionally connects to CA1 (Field CA1) MBA:382 · Mouse

Paired recordings showed that long-range inhibitory BA input reached NAc-projecting vH neurons, but with consistently smaller amplitude than in neighbouring BA-projecting neurons (7 pairs); the authors describe this as a weak connection.

Fig. 4G-I

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BLA (Basolateral amygdalar nucleus) MBA:295 projects to CA1 (Field CA1) MBA:382 · Mouse

In vGAT-cre::tdTomato reporter mice, a small but consistent fraction of amygdalar neurons retrogradely labelled from ventral hippocampus were vGAT-positive, and these inhibitory projection cells were intermingled with the excitatory ones across all amygdala nuclei and all anatomical axes.

Fig. 2A; Fig. 2—figure supplement 1A-C

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BLA (Basolateral amygdalar nucleus) MBA:295 functionally connects to CA1 (Field CA1) MBA:382 · Mouse

With ChR2 restricted to excitatory basal amygdala neurons by the CaMKii promoter, light evoked large currents at 0 mV in vH pyramidal cells that were completely abolished by NBQX, showing the inhibition was purely disynaptic feedforward inhibition driven by a glutamatergic BA input (n = 3 neurons).

Fig. 2F,G

Made by an AI model reading the paper (claude-opus-5, extract@0.3.0); a second AI model (claude-opus-5-5) disagrees. “Fig 2F,G records NBQX-sensitive inhibitory currents at 0 mV, so it does not show a direct excitatory connection onto pyramidal cells; the sign is wrong for this evidence.”

BLA (Basolateral amygdalar nucleus) MBA:295 functionally connects to CA1 (Field CA1) MBA:382 · Mouse

In 8 pairs of neighbouring PFC-projecting and BA-projecting vH neurons, light activation of pan-neuronal BA input produced essentially no excitatory current in the PFC-projecting cells while the BA-projecting partner responded.

Fig. 4D-F

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BLA (Basolateral amygdalar nucleus) MBA:295 functionally connects to CA1 (Field CA1) MBA:382 · Mouse

Recording from fluorescently identified vGAT+ interneurons in ventral hippocampus, light activation of BA axons evoked excitatory currents at -70 mV in about half of the interneurons tested.

Fig. 5A,B

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BLA (Basolateral amygdalar nucleus) MBA:295 projects to CA1 (Field CA1) MBA:382 · Mouse

Fluorescent cholera toxin B injected into ventral hippocampus retrogradely labelled many neurons in the basolateral amygdala; labelling was concentrated in posterior BLA together with posterior BMA.

Fig. 1B-D

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BLA (Basolateral amygdalar nucleus) MBA:295 functionally connects to CA1 (Field CA1) MBA:382 · Mouse

Light stimulation of basal amygdala axons expressing ChR2 pan-neuronally evoked currents at 0 mV in roughly 30% of vH pyramidal neurons that were blocked by gabazine. In 4 of 12 cells with inhibitory responses part of the current survived NBQX, indicating direct long-range inhibition in addition to feedforward inhibition.

Fig. 2D,E; Fig. 2—figure supplement 1D-F

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BLA (Basolateral amygdalar nucleus) MBA:295 functionally connects to CA1 (Field CA1) MBA:382 · Mouse

With cre-dependent ChR2 in GABAergic BA neurons, light-evoked inhibitory currents were consistently larger in BA-projecting vH neurons than in neighbouring NAc-projecting (7 pairs) or PFC-projecting (7 pairs) neurons.

Fig. 4G-L

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MEA (Medial amygdalar nucleus) MBA:403 projects to CA1 (Field CA1) MBA:382 · Mouse

Retrogradely labelled neurons projecting to ventral hippocampus were also found in the medial amygdala after cholera toxin B injection in vH.

Fig. 1B-D

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CA1 (Field CA1) MBA:382 projects to BLA (Basolateral amygdalar nucleus) MBA:295 · Mouse

Cholera toxin B injected into basal amygdala retrogradely labelled a separate population of ventral CA1/subiculum neurons, showing a reciprocal vH-to-BA projection.

Fig. 3A-D

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BMA (Basomedial amygdalar nucleus) MBA:319 projects to CA1 (Field CA1) MBA:382 · Mouse

Cholera toxin B injection in ventral hippocampus labelled neurons in the basomedial amygdala, with the densest labelling in its posterior part.

Fig. 1B-D

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CA1 (Field CA1) MBA:382 projects to ILA (Infralimbic area) MBA:44 · Mouse

Differently tagged cholera toxin B injected into prefrontal cortex labelled a population of neurons in the ventral CA1/subiculum border, which was largely non-overlapping with populations labelled from NAc or BA.

Fig. 3A-D

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BLA (Basolateral amygdalar nucleus) MBA:295 functionally connects to CA1 (Field CA1) MBA:382 · Mouse

With cre-dependent ChR2 confined to GABAergic basal amygdala neurons in vGAT-cre mice, light evoked robust currents at 0 mV in vH pyramidal neurons that were insensitive to NBQX but blocked by gabazine, demonstrating a direct long-range inhibitory connection (n = 6 neurons).

Fig. 2H,I

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BLA (Basolateral amygdalar nucleus) MBA:295 functionally connects to CA1 (Field CA1) MBA:382 · Mouse

In paired recordings of neighbouring retrogradely labelled vH neurons, light activation of pan-neuronal (and separately CaMKii-restricted) BA axons evoked excitatory currents at -70 mV in BA-projecting vH neurons; these were equal to those in neighbouring NAc-projecting cells and much larger than in PFC-projecting cells.

Fig. 4A-F; Fig. 5L-N

Made by an AI model reading the paper (claude-opus-5, extract@0.3.0); a second AI model (claude-opus-5-5) disagrees. “The paper reports no connection probability of 1.0 for vHBA cells; the paired designs used 9, 8 and 10 pairs, so this number is unsupported.”