POU6f1 Mediates Neuropeptide-Dependent Plasticity in the Adult Brain.

TitlePOU6f1 Mediates Neuropeptide-Dependent Plasticity in the Adult Brain.
Publication TypeJournal Article
Year of Publication2018
AuthorsMcClard, CK, Kochukov, MY, Herman, I, Liu, Z, Eblimit, A, Moayedi, Y, Ortiz-Guzman, J, Colchado, D, Pekarek, B, Panneerselvam, S, Mardon, G, Arenkiel, BR
JournalJ Neurosci
Volume38
Issue6
Pagination1443-1461
Date Published2018 Feb 07
ISSN1529-2401
Abstract

The mouse olfactory bulb (OB) features continued, activity-dependent integration of adult-born neurons, providing a robust model with which to examine mechanisms of plasticity in the adult brain. We previously reported that local OB interneurons secrete the neuropeptide corticotropin-releasing hormone (CRH) in an activity-dependent manner onto adult-born granule neurons and that local CRH signaling promotes expression of synaptic machinery in the bulb. This effect is mediated via activation of the CRH receptor 1 (), which is developmentally regulated during adult-born neuron maturation. CRHR1 is a G-protein-coupled receptor that activates CREB-dependent transcription in the presence of CRH. Therefore, we hypothesized that locally secreted CRH activates CRHR1 to initiate circuit plasticity programs. To identify such programs, we profiled gene expression changes associated with CRHR1 activity in adult-born neurons of the OB. Here, we show that CRHR1 activity influences expression of the brain-specific Homeobox-containing transcription factor POU Class 6 Homeobox 1 (). To elucidate the contributions oftoward activity-dependent circuit remodeling, we targeted CRHR1neurons in male and female mice for cell-type-specific manipulation ofexpression. Whereas loss ofin CRHR1neurons resulted in reduced dendritic complexity and decreased synaptic connectivity, overexpression ofin CRHR1neurons promoted dendritic outgrowth and branching and influenced synaptic function. Together, these findings suggest that the transcriptional program directed bydownstream of local CRH signaling in adult-born neurons influences circuit dynamics in response to activity-dependent peptide signaling in the adult brain.Elucidating mechanisms of plasticity in the adult brain is helpful for devising strategies to understand and treat neurodegeneration. Circuit plasticity in the adult mouse olfactory bulb is exemplified by both continued cell integration and synaptogenesis. We previously reported that these processes are influenced by local neuropeptide signaling in an activity-dependent manner. Here, we show that local corticotropin-releasing hormone (CRH) signaling induces dynamic gene expression changes in CRH receptor expressing adult-born neurons, including altered expression of the transcription factorWe further show thatis necessary for proper dendrite specification and patterning, as well as synapse development and function in adult-born neurons. Together, these findings reveal a novel mechanism by which peptide signaling modulates adult brain circuit plasticity.

DOI10.1523/JNEUROSCI.1641-17.2017
Alternate JournalJ. Neurosci.
PubMed ID29305536
PubMed Central IDPMC5815346
Grant ListS10 OD016167 / OD / NIH HHS / United States
R01 NS078294 / NS / NINDS NIH HHS / United States
U54 HD083092 / HD / NICHD NIH HHS / United States
P30 CA125123 / CA / NCI NIH HHS / United States
F31 NS092435 / NS / NINDS NIH HHS / United States