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Methodological
approach
During the last decade, the work of many research groups have provided compelling insight into the molecular and cellular mechanisms
responsible for the induction and stability of synaptic changes and the
acquisition and storage of new memories in the mammalian brain.
This achievement has been possible thanks to the convergence of very
different disciplines and methodologies. Our team uses an interdisciplinary approach to investigate the role of transcriptional and epigenetic mechanisms in neuronal plasticity and memory formation. We combine
bottom-up (based on the generation of genetically modified mice
and their parallel analysis at the biochemical, molecular,
electrophysiological and behavioral levels) and top-down approaches (based on the application of global techniques for the analysis of gene expression and chromatin remodelling in the brain of behaving animals) to investigate this challenging question.
Specifically, we are using the following methodologies:
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• Mouse genetics
We are currently working with diverse strains of genetically modified
mice, including inducible transgenic lines and conditional knockouts. |
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• Molecular and cell biology techniques
We use conventional techniques to analyze gene expression, such as
western-blot, immunohistochemistry, in situ hybridization, quantitative
RT-PCR, etc. We are also interested in investigating genome-wide
changes in gene expression and transcriptional regulation in vivo. To
this end, we are applying recent methodological advances in the field,
including last generation high-density oligonucleotide expression
arrays and chromatin
immunoprecipitation (ChIP) assays.
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• Electrophysiological studies
Our analysis of acute hippocampal slices includes measures of
neuronal excitability, intrinsic membrane properties and synaptic transmission
and plasticity.
Dr. Mikel Lopez de Armentia, a former member of the team, prepared this interesting
introductory video to electrophysiological recordings with the
collaboration of Stuart Ingham, INA's graphic designer (sorry, at the
moment, soundtrack is only available in Spanish). 
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• Behavioral studies
We have established a battery of behavioral tasks to
evaluate basic mouse behavior and, more precisely, to assess explicit
forms of memory. This battery includes fear conditioning, spatial
learning at the Morris water maze, object recognition, etc...
You can see here a video showing how a mouse learns to navigate in
the Morris water maze, a common task to evaluate learning and memory in
rodents. 
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