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3D Modeling of Dendritic Spines with Synaptic Plasticity

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Published on: May 18, 2020

CBP and SRF co-regulate dendritic growth and synaptic maturation.

Beatriz Del Blanco¹, Deisy Guiretti^1,2, Romana Tomasoni^1,3

¹Instituto de Neurociencias de Alicante (Universidad Miguel Hernández - Consejo Superior de Investigaciones Científicas), Av. Santiago Ramón y Cajal s/n, 03550, Sant Joan d'Alacant, Spain.

Cell Death and Differentiation

|March 10, 2019

Summary

CREB-binding protein (CBP) is crucial for neuronal development and maturation. Its loss impairs neuronal growth, synaptic plasticity, and leads to developmental defects, highlighting CBP-SRF interactions in brain development.

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Area of Science:

Neuroscience
Molecular Biology
Developmental Biology

Background:

CREB-binding protein (CBP) is a key regulator of gene transcription.
CBP plays critical roles in various developmental processes.
Its specific function in neuronal differentiation and maturation requires further investigation.

Purpose of the Study:

To investigate the consequences of selective CBP ablation in newborn and adult-born neurons.
To elucidate the role of CBP in neuronal growth, differentiation, and synaptic plasticity.
To explore the interaction between CBP and serum response factor (SRF) in neuronal development.

Main Methods:

Selective genetic ablation of CBP in mice during neuronal differentiation and in adult neuroprogenitors.
In vivo studies of perinatal lethality and diaphragm innervation.
In vitro studies of cultured neurons assessing outgrowth, spine morphology, and synaptic remodeling.
Transcriptional profiling to identify affected genes and regulatory pathways.

Main Results:

CBP ablation in newborn neurons caused perinatal death and defective diaphragm innervation.
Loss of CBP in adult dentate gyrus neuroprogenitors impaired neuronal growth and maturation.
Cultured neurons lacking CBP showed reduced outgrowth, immature spines, and impaired activity-dependent synaptic remodeling.
Transcriptional analysis revealed broad changes in genes related to neuronal growth and plasticity, including targets of CBP and SRF.
Enhancing SRF activity independently of CBP rescued transcriptional, synaptic, and growth defects.

Conclusions:

CBP is essential for the final stages of neuronal differentiation and maturation in both developing and adult brains.
CBP-SRF interactions are critical for neuronal outgrowth and synaptic plasticity.
CBP supports a vital gene program necessary for neuronal development and function.