Grupos y Lneas de Investigacin

Modulation of Neural Excitability and Synaptic Transmission and its role in Learning and Memory

Dr. David Fernández de Sevilla

Research Interests:

The cellular mechanisms underlying information processing leading to memory formation and learning is under intense debate. Research of our group focuses on the study of the mechanisms that regulate neural excitability and synaptic plasticity in the cerebral cortex and its role leaning and memory.

My previous work provided the demonstration that acetylcholine (ACh) is able to induce long term potentiation of glutamatergic synaptic transmission at CA1 pyramidal neurons of the hippocampus by increasing neuronal excitability and converting silent synapses into functional one through the insertion of glutamatergic AMPARs in its spines. Similarly we have proved that ACh is able to induce calcium spikes and potentiation of glutamatergic synaptic transmission at layer 5 pyramidal neurons of the barrel cortex.

Our current research lines aim to analyze:

  • the role of endocannabinoids  in the induction of calcium spikes and its effect on excitability and synaptic plasticity in the somatosensory cortex.
  • the mechanisms by which IGF-1 (insulin-like growth factor 1) modulates synaptic transmission and neuronal excitability in the prefrontal cortex and its function in the fear conditioning memory.

Most relevant Techniques:

  •     Intracellular recording using the Patch clamp technique in rat or mouse brain slices.
  •     Extracellular recordings of the field potential in vitro.
  •     Calcium imaging to monitor intracellular calcium activity of astrocytes and neurons.
  •     Optogenetics.
  •     Fear conditioned Behavioural test.
  •     Surgery of rats and mice.

Group Leader:

  • David Fernández de Sevilla PhD

Postdoctoral Researchers:

  • Laura Maglio PhD

Predoctoral Researchers:

  • Jose Antonio Noriega Prieto

Ongoing Collaborations:

       Washington Buño, PhD (Instituto Cajal CSIC, Madrid)

       Ángel Núñez, PhD (UAM, Madrid)

       Zafaruddin Khan, PhD (UMA, Malaga)

       Ignacio Torres Alemán (Instituto Cajal CSIC, Madrid)

Technicians:

  • Marta Callejo

Selected Publications:

  • Año : 2017

Maglio LE, Noriega-Prieto JA, Maraver MJ, Fernández de Sevilla D. (2017) Endocannabinoid-Dependent Long-Term Potentiation of Synaptic Transmission at Rat Barrel Cortex. Cereb Cortex. Mar 1:1-14. doi: 10.1093

Díez-García A, Barros-Zulaica N, Núñez Á, Buño W, Fernández de Sevilla D. (2017) Bidirectional Hebbian Plasticity Induced by Low-Frequency Stimulation in Basal Dendrites of Rat Barrel Cortex Layer 5 Pyramidal Neurons. Front Cell Neurosci. Feb 1;11:8. doi: 10.3389/fncel.2017.00008

Domínguez S, Fernández de Sevilla D, Buño W. (2017) Acetylcholine Facilitates a Depolarization-Induced Enhancement of Inhibition in Rat CA1 Pyramidal Neurons. Cereb Cortex. Nov 29. pii: bhv276.

  • Año : 2016

Domínguez S, Fernández de Sevilla D, Buño W. (2016) Muscarinic Long-Term Enhancement of Tonic and Phasic GABAA Inhibition in Rat CA1 Pyramidal Neurons. Front Cell Neurosci. Oct 26;10:244.

  • Año : 2014

Dominguez S, Fernández de Sevilla D, Buño W.(2014) Postsynaptic activity reverses the sign of the acetylcholine-induced long-term plasticity of GABAA inhibition. Proc Natl Acad Sci U S A. 111(26):E2741-50.

  • Año : 2013

Ahumada J, Fernández de Sevilla D, Couve A, Buño W, Fuenzalida M. (2013) Long-term depression of inhibitory synaptic transmission induced by spike-timing dependent plasticity requires coactivation of endocannabinoid and muscarinic receptors. Hippocampus. 23(12):1439-52.

  • Año : 2012

Nuñez A, Domínguez S, Buño W, Fernández de Sevilla D. (2012) Cholinergic-mediated response enhancement in barrel cortex layer V pyramidal neurons. J Neurophysiol.108(6):1656-68.

Navarrete M, Perea G, Fernandez de Sevilla D, Gómez-Gonzalo M, Núñez A, Martín ED, Araque A. (2012)  Astrocytes mediate in vivo cholinergic-induced synaptic plasticity. PLoS Biol. 10(2) e1001259

  • Año : 2010

Fernández de Sevilla D, Buño W. (2010) The muscarinic long-term enhancement of NMDA and AMPA receptor-mediated transmission at Schaffer collateral synapses develop through different intracellular mechanisms. J Neurosci. 30(33): 11032-42