Genetic labeling of axo-axonic cells in the basolateral amygdala

Nakashima, Miki; Morikawa, Shota; Ikegaya, Yuji

doi:10.1016/j.neures.2022.02.002

Cited by 7 publications

(3 citation statements)

References 32 publications

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“…VIP INs, that mediate feedforward disinhibition, respond primarily to salient sensory cues, while PV INs participate in both feedback and feedforward inhibition and exhibit functional properties of both SOM and VIP INs throughout our behavioral assay. Considering the subpopulations of PV cells reported 40–42 , it is possible that distinct subpopulations contribute to the mixed functional phenotypes of PV INs observed herein. For example, PV INs mediating feedback inhibition could exhibit in vivo activity patterns more akin to SOM INs (e.g.…”

Section: Discussionmentioning

confidence: 94%

Synaptic Organization-Function Relationships of Amygdala Interneurons Supporting Associative Learning

Báldi,

Muthuswamy,

Loomba

et al. 2024

Preprint

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SUMMARYCoordinated activity of basolateral amygdala (BLA) GABAergic interneurons (INs) and glutamatergic principal cells (PCs) is critical for associative learning, however the microcircuit organization-function relationships of distinct IN classes remain uncertain. Here, we show somatostatin (SOM) INs provide inhibition onto, and are excited by, local PCs, whereas vasoactive intestinal peptide (VIP) INs are driven by extrinsic afferents. Parvalbumin (PV) INs inhibit PCs and are activated by local and extrinsic inputs. Thus, SOM and VIP INs exhibit complementary roles in feedback and feedforward inhibition, respectively, while PV INs contribute to both microcircuit motifs. Functionally, each IN subtype reveals unique activity patterns across fear- and extinction learning with SOM and VIP INs showing most divergent characteristics, and PV INs display an intermediate phenotype parallelling synaptic data. Finally, SOM and PV INs dynamically track behavioral state transitions across learning. These data provide insight into the synaptic microcircuit organization-function relationships of distinct BLA IN classes.

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Section: Discussionmentioning

confidence: 94%

Synaptic Organization-Function Relationships of Amygdala Interneurons Supporting Associative Learning

Báldi,

Muthuswamy,

Loomba

et al. 2024

Preprint

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“…Yet, none of these driver lines have been shown to be specific and comprehensive. For example, the Vipr2 -Cre driver captures a subset of neocortical and basolateral amygdala (BLA) AACs, but is not entirely specific in these areas ( Daigle et al, 2018 ; Nakashima et al, 2022 ; Tasic et al, 2018 ). Similarly, our Unc5b CreER line enabled adeno-associated virus (AAV) targeting of hippocampal AACs, but also labels endothelial cells when combined with a reporter line ( Dudok et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Specific and comprehensive genetic targeting reveals brain-wide distribution and synaptic input patterns of GABAergic axo-axonic interneurons

Raudales,

Kim,

Kelly

et al. 2024

eLife

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Axo-axonic cells (AACs), also called chandelier cells (ChCs) in the cerebral cortex, are the most distinctive type of GABAergic interneurons described in the neocortex, hippocampus, and basolateral amygdala (BLA). AACs selectively innervate glutamatergic projection neurons (PNs) at their axon initial segment (AIS), thus may exert decisive control over PN spiking and regulate PN functional ensembles. However, the brain-wide distribution, synaptic connectivity, and circuit function of AACs remains poorly understood, largely due to the lack of specific and reliable experimental tools. Here, we have established an intersectional genetic strategy that achieves specific and comprehensive targeting of AACs throughout the mouse brain based on their lineage ( Nkx2.1 ) and molecular ( Unc5b , Pthlh ) markers. We discovered that AACs are deployed across essentially all the pallium-derived brain structures, including not only the dorsal pallium-derived neocortex and medial pallium-derived hippocampal formation, but also the lateral pallium-derived claustrum-insular complex, and the ventral pallium-derived extended amygdaloid complex and olfactory centers. AACs are also abundant in anterior olfactory nucleus, taenia tecta and lateral septum. AACs show characteristic variations in density across neocortical areas and layers and across subregions of the hippocampal formation. Neocortical AACs comprise multiple laminar subtypes with distinct dendritic and axonal arborization patterns. Retrograde monosynaptic tracing from AACs across neocortical, hippocampal and BLA regions reveal shared as well as distinct patterns of synaptic input. Specific and comprehensive targeting of AACs facilitates the study of their developmental genetic program and circuit function across brain structures, providing a ground truth platform for understanding the conservation and variation of a bona fide cell type across brain regions and species.

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“…Yet, none of these driver lines have been shown to be specific and comprehensive. For example, the Vipr2-ires-Cre driver captures a subset of neocortical and basolateral amygdala (BLA) AACs, but is not entirely specific in these areas (Daigle et al, 2018; Nakashima et al, 2022; Tasic et al, 2018). Similarly, our Unc5b-CreER line enabled AAV targeting of hippocampal AACs, but also labels endothelial cells when combined with a reporter line (Dudok et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Specific and comprehensive genetic targeting reveals brain-wide distribution and synaptic input patterns of GABAergic axo-axonic interneurons

Raudales,

Kim,

Kelly

et al. 2023

Preprint

View full text Add to dashboard Cite

Axo-axonic cells (AACs), also called chandelier cells (ChCs) in the cerebral cortex, are the most distinctive type of GABAergic interneurons described in the neocortex, hippocampus, and basolateral amygdala (BLA). AACs selectively innervate glutamatergic projection neurons (PNs) at their axon initial segment (AIS), thus may exert decisive control over PN spiking and regulate PN functional ensembles. However, the brain-wide distribution, synaptic connectivity, and circuit function of AACs remains poorly understood, largely due to the lack of specific and reliable experimental tools. Here, we have established an intersectional genetic strategy that achieves specific and comprehensive targeting of AACs throughout the mouse brain based on their lineage (Nkx2.1) and molecular (Unc5b,Pthlh) markers. We discovered that AACs are deployed across essentially all the pallium-derived brain structures, including not only the dorsal pallium-derived neocortex and medial pallium-derived hippocampal formation, but also the lateral pallium-derived claustrum-insular complex, and the ventral pallium-derived extended amygdaloid complex and olfactory centers. AACs are also abundant in anterior olfactory nucleus, taenia tecta and lateral septum. AACs show characteristic variations in density across neocortical areas and layers and across subregions of the hippocampal formation. Neocortical AACs comprise multiple laminar subtypes with distinct dendritic and axonal arborization patterns. Retrograde monosynaptic tracing from AACs across neocortical, hippocampal and BLA regions reveal shared as well as distinct patterns of synaptic input. Specific and comprehensive targeting of AACs facilitates the study of their developmental genetic program and circuit function across brain structures, providing a ground truth platform for understanding the conservation and variation of a bona fide cell type across brain regions and species.

show abstract

Genetic labeling of axo-axonic cells in the basolateral amygdala

Cited by 7 publications

References 32 publications

Synaptic Organization-Function Relationships of Amygdala Interneurons Supporting Associative Learning

Synaptic Organization-Function Relationships of Amygdala Interneurons Supporting Associative Learning

Specific and comprehensive genetic targeting reveals brain-wide distribution and synaptic input patterns of GABAergic axo-axonic interneurons

Specific and comprehensive genetic targeting reveals brain-wide distribution and synaptic input patterns of GABAergic axo-axonic interneurons

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