Connectome of the Suprachiasmatic Nucleus: New Evidence of the Core-Shell Relationship

Oct 5, 2018eNeuro

Brain network of the body’s internal clock showing new details about its core and outer parts

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Abstract

The brain clock in wild-type mice exhibits specific communication patterns among different peptidergic neuron types in the hypothalamic suprachiasmatic nucleus (SCN).

Connections between core and shell neurons in the SCN involve distinct peptidergic cell types, indicating specialized communication.
AVP fibers show sparse contacts with VIP neurons, while VIP neurons make numerous contacts back to AVP neurons.
AVP fibers have more connections to GRP neurons compared to the reverse direction.
In VIP-deficient mice, AVP expression is significantly reduced in the SCN but remains unchanged in other hypothalamic regions.
Colchicine treatment can restore AVP neuron numbers in VIP-deficient mice to levels seen in wild-type mice.

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A brain clock, constituted of ∼20,000 peptidergically heterogeneous neurons, is located in the hypothalamic suprachiasmatic nucleus (SCN). While many peptidergic cell types have been identified, little is known about the connections among these neurons in mice. We first sought to identify contacts among major peptidergic cell types in the SCN using triple-label fluorescent immunocytochemistry (ICC). To this end, contacts among vasoactive intestinal polypeptide (VIP), gastrin-releasing peptide (GRP), and calretinin (CALR) cells of the core, and arginine vasopressin (AVP) and met-enkephalin (ENK) cells of the shell were analyzed. Some core-to-shell and shell-to-core communications are specialized. We found that in wild-type (WT) mice, AVP fibers make extremely sparse contacts onto VIP neurons but contacts in the reverse direction are numerous. In contrast, AVP fibers make more contacts onto GRP neurons than conversely. For the other cell types tested, largely reciprocal connections are made. These results point to peptidergic cell type-specific communications between core and shell SCN neurons. To further understand the impact of VIP-to-AVP communication, we next explored the SCN in VIP-deficient mice (VIP-KO). In these animals, AVP expression is markedly reduced in the SCN, but it is not altered in the paraventricular nucleus (PVN) and supraoptic nucleus (SON). Surprisingly, in VIP-KO mice, the number of AVP appositions onto other peptidergic cell types is not different from controls. Colchicine administration, which blocks AVP transport, restored the numbers of AVP neurons in VIP-KO to that of WT littermates. The results indicate that VIP has an important role in modulating AVP expression levels in the SCN in this mouse.

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Connectome of the Suprachiasmatic Nucleus: New Evidence of the Core-Shell Relationship

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