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Inhibition of cAMP response element-binding protein reduces neuronal excitability and plasticity, and triggers

Dragana Jancic1, Mikel Lopez de Armentia, Luis M Valor

  • 1Instituto de Neurociencias de Alicante (Universidad Miguel Hernández-Consejo Superior de Investigaciones Científicas), Campus de Sant Joan, 03550 Alicante, Spain.

Cerebral Cortex (New York, N.Y. : 1991)
|February 14, 2009
PubMed

Insights

The cAMP-responsive element-binding protein (CREB) pathway is crucial for neuronal plasticity, learning, and survival. Inhibiting CREB in mice impaired learning and caused significant neuron loss, confirming its vital role.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • The cAMP-responsive element-binding protein (CREB) pathway regulates gene expression critical for neuronal function.
  • CREB is implicated in neuronal plasticity, learning, and survival.

Purpose of the Study:

  • To investigate the in vivo role of CREB-dependent gene expression in neuronal plasticity and survival.
  • To analyze the effects of CREB inhibition on hippocampal function and neuronal health.

Main Methods:

  • Generated bitransgenic mice expressing a regulatable CREB inhibitor (A-CREB) in forebrain neurons.
  • Assessed hippocampal long-term potentiation (LTP), neuronal excitability, seizure susceptibility, and gene expression.
  • Evaluated long-term effects of chronic CREB inhibition on neuronal survival.

Main Results:

  • A-CREB expression in hippocampal neurons impaired L-LTP and reduced intrinsic excitability.
  • Inhibition of CREB altered basal and activity-driven gene expression and decreased seizure susceptibility.
  • Chronic CREB inhibition led to severe neuronal loss in the hippocampus (CA1) and other brain regions.

Conclusions:

  • CREB-dependent gene expression plays a dual role in regulating intrinsic and synaptic plasticity.
  • CREB is essential for maintaining neuronal survival, particularly in the hippocampus.
  • These findings reinforce the critical role of CREB in learning, memory, and neuronal health.

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