A novel molecular mechanism key to associative memory encoding in the hippocampus has been uncovered by a team led by Dr Carlos Saura from the Institut de Neurociències (INc) at the Universitat Autònoma de Barcelona. This brain region is highly affected pathologically at early stages of several neurodegenerative diseases, including Alzheimer´s disease.

Associative memory is used to store and remember situations, places and people long term. This study shows that a protein called CREB-regulated transcription coactivator 1 (CRTC1), which regulates genes essential for neuron function, needs to be activated in the hippocampus so that associative memory can be processed and stored.

In earlier studies, the research group showed that CRTC1 was disrupted in the brain of Alzheimer´s patients at early disease stages. Indeed, associative memory is one of the first cognitive abilities altered in dementia patients.

The new study reveals that disruption of CRTC1 function also occurs while neurodegeneration is occurring.

Memory Loss Reversed

To restore CRTC1 function, researchers used a gene therapy approach to introduce copies of this gene in a group of neurons in the hippocampus of a mouse model of neurodegeneration. Mice that have already memory deficits and neuropathology and treated with this gene-therapy approach were able to remember a negative experience that they had in the past.

Mice that received an innocuous treatment did not remember the experience and they behaved normally. Saura explains:

“The relevance of this discovery is that activation of specific neurons of the hippocampus reverses memory loss even at late stages of neurodegeneration."

The study provides important knowledge on the molecular bases of memory processing in normal and pathological conditions, especially in memory disorders.

“These results are exciting since provide strong support for potential translational applications in the clinic because this molecular mechanism could be a new target to reverse memory decline in dementia,” said Dr. Saura.

Parra-Damas, Arnaldo et al. CRTC1 Function During Memory Encoding Is Disrupted in Neurodegeneration Biological Psychiatry , Volume 81 , Issue 2 , 111 - 123

Top Image: CRTC1 activation (green) on neurons (blue) after a memory test. Credit: UAB

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