Lab Members

2017. From left to right: Diego Asua (undergraduate student), Raul Escribano (Technician), Shira Knafo (PI), Alberto Ouro (PhD) and Ghassen Bougamra (graduate student)

Sitting: Maria Calleja (graduate student) and Maria Ulloa (undergraduate student).

Dr. Miguel Morales and Dr. Alberto Ouro at the lab (2018)

Dr. Alberto Ouro in a lab meeting (2018)

Diego Asua in a lab meeting (2017)

Dr. Miguel Morales at the rig (2018)

Maria Calleja in a lab meeting (2018)

Maria Ulloa in a lab meeting (2018)

Alain Castaño in a lab meeting (2018)

Dr. Cristina Sanchez-Puelles and Shira Knafo on Cristina's Thesis defense (2017)

2016. From left to right: Alberto Ouro (PhD), Shira Knafo (PI), Igotz Delgado (PhD= Maria Calleja (graduate student) and Raul Escribano (technician)

2016. From left to right: Diego Asua (undergraduate student), Miguel Morales (PhD), Alberto Ouro (PhD), Shira Knafo (PI), Maria Calleja (graduate student) and Ghassen Bougamra (visitng student)

2014. From left to right: Shira Knafo (PI), Igotz Delgado (postdoc), Cristina Sanchez-Puelles (graduate student), Ianire diaz and Maria Calleja (graduate student)

2014. From left to right: Maria Calleja (graduate student), , Ianire diaz (Visitng) Cristina Sanchez-Puelles (graduate student) and Igotz Delgado (postdoc).

Shira Knafo, MD, PhD, principal investigator, email: This email address is being protected from spambots. You need JavaScript enabled to view it.

Miguel Morales, PhD, Senior Research Associate

Alberto Ouro, PhD, Postdoctoral fellow

María Calleja, M.Sci., Graduate Student

Former members of the lab

Diego Asua, undergraduate student

Maria Olluo, undergraduate student

Alain Lopez , undergraduate student

Dr. Cristina Sanchez-Puelles

Dr. Igotz Delgado

News

Paper in Nature Neuroscience

Neurons communicate with one another by synaptic connections, where information is exchanged from one neuron to its neighbor. These connections are not static, but are continuously modulated in response to the ongoing activity (or experience) of the neuron. This process, known as synaptic plasticity, is a fundamental mechanism for learning and memory in humans as in all animals. In fact, we now know that alterations in synaptic plasticity are responsible for memory impairment in cognitive disorders such as Alzheimer’s disease. Nevertheless, the mechanisms by which these alterations take place are still starting to be uncovered.

This new research work, published in Nature Neuroscience reports that in Alzheimer’s disease, synaptic plasticity is altered by a protein originally described as a tumor suppressor: PTEN. In 2010, the research group of Dr. Esteban discovered that PTEN is recruited to synapses during normal (physiological) synaptic plasticity. This new investigation by Drs. Knafo, Venero and Esteban, now indicates that this mechanism runs uncontrolled during Alzheimer’s disease. One of the pathological agents of the disease, the beta-amyloid, drives PTEN into synapses excessively, unbalancing the mechanisms for synaptic plasticity and impairing memory formation.

An important aspect of this study is that it also describes how PTEN is recruited to synapses in response to beta-amyloid, and proposes a strategy to prevent it. Using a mouse model of Alzheimer’s disease, the investigators developed a molecular tool to shield synapses from the recruitment of PTEN. With this tool, neurons are rendered resistant to beta-amyloid, and Alzheimer’s mice preserve their memory.

Although this is basic research using animal models, these studies contribute to dissect the mechanisms that control our cognitive function, and orient us towards potential therapeutic avenues for mental diseases where these mechanisms are deficient.

Paper in PLoS Biology

From the web: "A recent study in PLoS Biology should give hope to the forgetful. A collaborative research group in Europe, spanning Spain, Switzerland and Denmark, developed a small protein called FGL that enhances memory formation and learning in rats, and now they have some explanation as to why. The study’s authors, led by Shira Knafo, César Venero and José Esteban, attribute the improvement from FGL to better connections—and ability to strengthen those connections—between neurons. This knowledge may eventually improve treatment of some disorders, as the authors explain that these “mechanisms are thought to be responsible for multiple cognitive deficits, such as autism and Alzheimer’s disease”

How it might work

In their most recent article, the authors suggest that FGL improves the brain's ability to modify the connections between neurons, the cells that are the building blocks of the brain. When examining neurons that had been treated with FGL, Knafo, Venero and Esteban found that they had higher levels of a receptor, AMPA, critical for modifying neuronal connections.

As the authors write, "The human brain contains trillions of neuronal connections, called synapses, whose pattern of activity controls all our cognitive functions. These synaptic connections are dynamic and constantly changing in their strength and properties, and this process of synaptic plasticity is essential for learning and memory. In this study, we show that synapses can be made more plastic using a small protein."

Many neuroscientists consider understanding plasticity the Holy Grail for learning and memory; once we understand plasticity, we will understand how the brain learns.