Biology subjects

Fernandez de Sevilla, D.

Publications and source records attributed to Fernandez de Sevilla, D..

4 recordsLinked to original sources

bioRxiv2023

Bidirectional Modulation Of Synaptic Transmission By Insulin-Like Growth Factor I

Insulin-like growth factor-I (IGF-I) plays a key role in the modulation of synaptic plasticity, and is an essential factor in learning and memory processes. Indeed, we have demonstrated that IGF-IR activation induces long-term potentiation (LTP) of synaptic transmission (LTPIGF-I) both in the barrel cortex, improving object recognition (Noriega-Prieto et al., 2021), and in the prefrontal cortex, facilitating the extinction of conditioned fear (Maglio et al., 2021). However, during aging, IGF-I levels are decreased, and the effect of this decrease in the induction of synaptic plasticity remains unknown. Here we show that the induction of NMDAR-dependent LTP at layer 2/3 PNs of the mouse barrel cortex is favored or prevented by IGF-I (10nM) or IGF-I (7nM), respectively, when IGF-I is applied 1 hour before the induction of Hebbian LTP. Analyzing the cellular basis of this bidirectional control of synaptic plasticity, we observed that while 10nM IGF-I generates LTP (LTPIGF-I) of the post-synaptic potentials (PSPs) by inducing LTD of the inhibitory post-synaptic currents (IPSCs), 7nM IGF-I generates LTD of the PSPs (LTDIGF-I) by inducing LTD of the excitatory post-synaptic currents (EPSCs). This bidirectional effect of IGF-I is supported by the observation of IGF-IR immunoreactivity at both excitatory and inhibitory synapses. Therefore, IGF-I controls the induction of Hebbian NMDAR-dependent plasticity depending on its concentration, revealing novel cellular mechanisms of IGF-I on synaptic plasticity and in the learning and memory machinery of the brain. SIGNIFICANCE STATEMENTInsulin-like growth factor-I (IGF-I) signalling plays key regulatory roles in multiple processes of brain physiology, such as learning and memory, and brain pathology, such as Alzheimer disease. Yet, the underlying mechanisms remain largely undefined. Here we demonstrate that IGF-I signalling triggers long-term potentiation (LTP) or long-term depression (LTD) of synaptic transmission at cortical synapses in a concentration dependent manner, thus regulating the induction of Hebbian synaptic plasticity. The present work represents an important conceptual advance in our knowledge of the cellular basis of IGF-I signalling in brain function.

neuroscience↗

bioRxiv2023

GENERATION OF FUNCTIONAL NEURONS FROM ADULT HUMAN MUCOSAL OLFACTORY ENSHEATHING GLIA BY DIRECT LINEAGE CONVERSION

A recent approach to promote central nervous system (CNS) regeneration after injury or disease is direct conversion of somatic cells to neurons. This is achieved by transduction of viral vectors that express neurogenic transcription factors. In this work we propose adult human mucosal olfactory ensheathing glia (hmOEG) as a candidate for direct reprogramming to neurons due to its accessibility and to its well-characterized neuro-regenerative capacity. After induction of hmOEG with the single neurogenic transcription factor NEUROD1, the cells under study exhibited morphological and immunolabeling neuronal features, fired action potentials and expressed glutamatergic and GABAergic markers. In addition, after engraftment of transduced hmOEG cells in mouse hippocampus, these cells showed specific neuronal labeling. Thereby, if we add to the neuro-regenerative capacity of hmOEG cultures the conversion to neurons of a fraction of their population through reprogramming techniques, the engraftment of hmOEG and hmOEG induced neurons could be a procedure to enhance neural repair after central nervous system injury.

neuroscience↗

bioRxiv2020

IGF-1 facilitates extinction of conditioned fear

Insulin-like growth factor-1 (IGF-1) plays a key role in synaptic plasticity, degenerative diseases, spatial learning, and anxiety-like behavioral processes. While IGF-1 regulates neuronal activity in many areas of the brain, its effect on synaptic plasticity and animal behavior dependent on the prefrontal cortex remain unexplored. Here, we show that IGF-1 induces a long-lasting depression of the medium and slow post-spike afterhyperpolarization (mAHP and sAHP), increasing the excitability of layer 5 pyramidal neurons of the infralimbic cortex. Besides, IGF-1 mediates a long-term depression of both inhibitory and excitatory synaptic transmission that results in a longterm potentiation of the postsynaptic potentials. We demonstrate that these synaptic and intrinsic regulatory processes mediated by IGF-1 favor the fear extinction memory. These results show novel functional consequences of IGF-1 signaling on animal behavior tasks dependent on the prefrontal cortex, revealing IGF-1 as a key element in the control of the fear extinction memory. Impact StatementIGF-1 modulates the neuronal firing and synaptic plasticity in infralimbic cortex, favoring the extinction memory

neuroscience↗

bioRxiv2020

IGF-I Governs Cortical Inhibitory Synaptic Plasticity By Astrocyte Activation

Insulin-like growth factor-I (IGF-I) signaling plays key regulatory roles in multiple processes of brain physiology and pathology. While the direct effects of IGF-I in neurons have been extensively studied, the astrocyte involvement in IGF-I signaling and the consequences on synaptic plasticity and animal behavior remain unknown. Here we show that IGF-I induces the long-term depression (LTD) of inhibitory synaptic transmission in the mouse barrel cortex. This LTD requires the activation of the IGF-I receptor (IGF-IR) in astrocytes, which stimulates astrocyte Ca2+ signaling and the release of ATP/adenosine that in turn activates A2A adenosine receptors at presynaptic inhibitory terminals. Specific deletion of IGF-IR in cortical astrocytes (IGF-IR-/-) impaired the behavioral performance in a whisker discrimination task. These results show novel mechanisms and functional consequences of IGF-I signaling on cortical inhibitory synaptic plasticity and animal behavior, revealing astrocytes as key elements in these processes.

neuroscience↗