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Synaptic proteomics as a means to identify the molecular basis of mental illness: Are we getting there?

Synapses are centrally involved in many brain disorders, particularly in psychiatric and neurodevelopmental ones. However, our current understanding of the proteomic alterations affecting synaptic performance in the majority of mental illnesses is limited. As a result, novel pharmacotherapies with improved neurological efficacy have been scarce over the past decades.

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Synaptic circuits associated with social interactions are affected in an autism mouse model

Social cognition is an important human skill frequently impaired in several neurodevelopmental disorders, including autism. Human genetic approaches have led to the identification of a number of genes associated with autism. However, how mutations in autism-associated genes affect the synaptic circuits of specific brain areas relevant for social interaction are not known. To identify synaptic […]

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Experimental induction of trans-synaptic long-term potentiation

Since the early 70’s of the past century, long-term potentiation (LTP) evoked experimentally by high-frequency stimulation (HFS) protocols is a popular technique for the study of cellular and molecular mechanisms underlying learning-dependent changes in synaptic strength. It was described for the first time in the hippocampus of anesthetized rabbits, but these seminal studies were followed […]

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Identification of layer-specific markers of hippocampal neurons

The hippocampus exhibits a huge genetic heterogeneity not only along the septo-temporal axis, but regionally from different subdivisions of CA1, CA2 and CA3 and from deep to superficial locations along the cornu ammonis. These genetic gradients link to differential contribution of hippocampal regions to cognitive processes such as episodic and spatial memory, and in hippocampal-specific […]

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Biochemical, cellular and physiological alterations of the glutamatergic synapse in a trisomic mouse model of Down syndrome

Along this project, we have explored the alterations of the glutamatergic synapse of the Ts65Dn mouse model of Down syndrome. We have fully characterized the proteomic and phosphoproteomic profile of subsynaptic fractions of the hippocampi of trisomic mice. Along this approach, we characterized candidate residues of the glutamate ionotropic receptors that are altered in trisomic […]

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DYRK1A-mediated phosphorylation of GluN2A at Ser(1048) regulates the surface expression and channel activity of GluN1/GluN2A receptors.

N-methyl-D-aspartate glutamate receptors (NMDARs) play a pivotal role in neural development and synaptic plasticity, as well as in neurological disease. Since NMDARs exert their function at the cell surface, their density in the plasma membrane is finely tuned by a plethora of molecules that regulate their production, trafficking, docking and internalization in response to external stimuli.

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