Sensory Experience Engages Microglia to Shape Neural Connectivity through a Non-Phagocytic Mechanism.


Journal

Neuron
ISSN: 1097-4199
Titre abrégé: Neuron
Pays: United States
ID NLM: 8809320

Informations de publication

Date de publication:
11 11 2020
Historique:
received: 22 07 2019
revised: 10 05 2020
accepted: 05 08 2020
pubmed: 16 9 2020
medline: 29 12 2020
entrez: 15 9 2020
Statut: ppublish

Résumé

Sensory experience remodels neural circuits in the early postnatal brain through mechanisms that remain to be elucidated. Applying a new method of ultrastructural analysis to the retinogeniculate circuit, we find that visual experience alters the number and structure of synapses between the retina and the thalamus. These changes require vision-dependent transcription of the receptor Fn14 in thalamic relay neurons and the induction of its ligand TWEAK in microglia. Fn14 functions to increase the number of bulbous spine-associated synapses at retinogeniculate connections, likely contributing to the strengthening of the circuit that occurs in response to visual experience. However, at retinogeniculate connections near TWEAK-expressing microglia, TWEAK signals via Fn14 to restrict the number of bulbous spines on relay neurons, leading to the elimination of a subset of connections. Thus, TWEAK and Fn14 represent an intercellular signaling axis through which microglia shape retinogeniculate connectivity in response to sensory experience.

Identifiants

pubmed: 32931754
pii: S0896-6273(20)30609-7
doi: 10.1016/j.neuron.2020.08.002
pmc: PMC7666095
mid: NIHMS1620438
pii:
doi:

Substances chimiques

Cytokine TWEAK 0
TWEAK Receptor 0
Tnfrsf12a protein, mouse 0
Tnfsf12 protein, mouse 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

451-468.e9

Subventions

Organisme : NIMH NIH HHS
ID : R00 MH120051
Pays : United States
Organisme : NIMH NIH HHS
ID : RF1 MH114047
Pays : United States
Organisme : NINDS NIH HHS
ID : P30 NS072030
Pays : United States
Organisme : NIMH NIH HHS
ID : K99 MH120051
Pays : United States
Organisme : NINDS NIH HHS
ID : R21 NS085320
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS028829
Pays : United States
Organisme : NEI NIH HHS
ID : P30 EY012196
Pays : United States

Commentaires et corrections

Type : CommentIn
Type : CommentIn

Informations de copyright

Copyright © 2020 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Interests L.C.B. and K.A.E. are employees and shareholders of Biogen.

Auteurs

Lucas Cheadle (L)

Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA.

Samuel A Rivera (SA)

Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA.

Jasper S Phelps (JS)

Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA; Program in Neuroscience, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA.

Katelin A Ennis (KA)

Research and Early Development, Biogen, 115 Broadway, Cambridge, MA 04142, USA.

Beth Stevens (B)

Department of Neurology, F.M. Kirby Neurobiology Center, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA.

Linda C Burkly (LC)

Research and Early Development, Biogen, 115 Broadway, Cambridge, MA 04142, USA.

Wei-Chung Allen Lee (WA)

Department of Neurology, F.M. Kirby Neurobiology Center, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA.

Michael E Greenberg (ME)

Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA. Electronic address: michael_greenberg@hms.harvard.edu.

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Classifications MeSH