CREB binding protein is required for both short-term and long-term memory formation

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• CREB binding protein (CBP) acts as a transcriptional coactivator and possesses histone acetyltransferase activity.
• Previous research indicated CBP as a potential target of presenilins in memory and neuronal survival regulation.

Purpose of the Study:

• To investigate the specific role of CBP in the adult brain, particularly in memory formation.
• To generate and analyze conditional knock-out (cKO) mice lacking CBP in forebrain excitatory neurons.

Main Methods:

• Generation of CBP conditional knock-out (cKO) mice with CBP inactivated in postnatal forebrain excitatory neurons.
• Histological analysis to assess neuronal morphology and degeneration.
• Behavioral testing for spatial, associative, and object-recognition memory (short- and long-term).
• Administration of trichostatin A (a histone deacetylase inhibitor) to assess rescue effects.
• Microarray and Western blot analyses to examine gene and protein expression.

Main Results:

• CBP cKO mice showed normal neuronal morphology and no age-dependent degeneration.
• Significant impairments in spatial, associative, and object-recognition memory (both short- and long-term) were observed in CBP cKO mice.
• Histone deacetylase inhibitor treatment did not rescue memory deficits.
• Decreased expression of calcium-calmodulin-dependent kinase isoforms and NMDA/AMPA receptor subunits in the cerebral cortex of CBP cKO mice.

Conclusions:

• CBP plays a crucial role in the formation of both short-term and long-term memory in the adult brain.
• The memory deficits in CBP cKO mice are likely not due to a general reduction in histone acetyltransferase activity.
• CBP influences memory formation through mechanisms involving the regulation of specific gene and protein expression, including components of synaptic plasticity.