Abstract
The central extended amygdala (EAc) is a forebrain macrosystem which has been widely implicated in fear, anxiety and pain. Its two key structures, the lateral bed nucleus of the stria terminalis (STL) and the central nucleus of amygdala (CeA), share similar mesoscale connectivity. However, it is not known whether they also share similar cell-specific neuronal circuits. We addressed this question using tract-tracing and immunofluorescence to reveal the connectivity of two neuronal populations expressing either protein kinase C delta (PKCδ) or somatostatin (SOM). PKCδ and SOM are expressed predominantly in the dorsal part of STL (STLD) and in the lateral/capsular parts of CeA (CeL/C). We found that, in both STLD and CeL/C, PKCδ+ cells are the main recipient of extra-EAc inputs from the external lateral part of the parabrachial nucleus (LPBE), while SOM+ cells are the sources of long-range projections to extra-EAc targets, including LPBE and periaqueductal gray. PKCδ+ cells can also integrate inputs from posterior basolateral nucleus of amygdala or insular cortex. Within EAc, PKCδ+, but not SOM+ neurons, serve as the major source of projections to the ventral part of STL and to the medial part of CeA. However, both cell types mediate interconnections between STLD and CeL/C. These results unveil the pivotal positions of PKCδ and SOM neurons in organizing parallel cell-specific neuronal circuits of CeA and STL, which further support the idea of EAc as a structural and functional macrostructure.
Footnotes
- Abbreviations
- ac
- anterior commissure
- ASt
- amygdalostriatal transition area
- BDA
- biotin dextran amine, 10000 MW
- BL
- basolateral nucleus of the amygdala
- BLA
- basolateral nucleus of the amygdala, anterior
- BLP
- basolateral nucleus of the amygdala, posterior
- BMP
- basomedial nucleus of the amygdala, posterior
- Calcrl
- calcitonin receptor-like
- CARD
- combined catalyzed reporter deposition
- CeA
- central nucleus of the amygdala
- CeC
- central nucleus of the amygdala, capsular part
- CeL
- central nucleus of the amygdala, lateral part
- CeL/C
- central nucleus of the amygdala, lateral and capsular part
- CeM
- central nucleus of the amygdala, medial part
- CGRP
- calcitonin gene-related peptide
- CGRPR
- calcitonin gene-related peptide receptor
- CPu
- caudate putamen
- CRF
- corticotropin-releasing factor
- cst
- commissural stria terminalis
- CTb
- cholera toxin B subunit
- D2R
- dopamine receptor D2
- DAPI
- 4’,6-Diamidino-2-Phenylindole, Dihydrochloride
- DMPAG
- dorsomedial periaqueductal gray
- DR
- dorsal rahpe nucleus
- EAc
- central extended amygdala
- ENK
- enkephalin
- FG
- Fluorogold
- Fu
- fusiform nucleus
- GI/DI
- granular and dysgranular insular cortex terminalis
- GP
- globus pallidus
- Htr2a
- serotonin receptor 2a
- i.p.
- intraperitoneal injection
- InsCx
- insular cortex
- KLH
- keyhole limpet hemocyanin
- LaVM
- lateral nucleus of amygdala, ventromedial
- LPAG
- lateral periaqueductal gray
- LPB
- lateral parabrachial nucleus
- LPBE
- external lateral parabrachial nucleus
- MPB
- medial parabrachial nucleus
- NPY
- neuropeptide Y
- PAG
- periaqueductal gray
- PB
- phosphate buffer
- PBS
- phosphate-buffered saline
- PHA-L
- Phaseolus vulgaris leucoagglutinin
- Pir
- piriform cortex
- PKCδ
- protein kinase C, delta type
- Ppp1r1b
- phosphatase 1 regulatory subunit 1B positive
- Rspo2
- R-spondin 2 positive
- s.c.
- subcutaneous injection
- S2
- secondary somatosensory cortex
- scp
- superior cerebellar peduncle
- SEM
- standard error of the mean
- SOM
- somatostatin
- ST
- bed nucleus of the stria terminalis
- STL
- lateral bed nucleus of the stria terminalis
- STLD
- dorsal lateral bed nucleus of the stria terminalis
- STLP
- posterior lateral bed nucleus of the stria terminalis
- STLV
- ventral lateral bed nucleus of the stria terminalis
- STMA
- anterior medial bed nucleus of the stria terminalis
- STMV
- ventral medial bed nucleus of the stria terminalis
- VLPAG
- ventral lateral periaqueductal gray