Person: Muñoz Céspedes, Alberto
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First Name
Alberto
Last Name
Muñoz Céspedes
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Ciencias Biológicas
Department
Biología Celular
Area
Biología Celular
Identifiers
2 results
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Item High levels of 27‑hydroxycholesterol results in synaptic plasticity alterations in the hippocampus(Scientific Reports, 2021) Loera‑Valencia, Raul; Vazquez‑Juarez, Erika; Muñoz Céspedes, Alberto; Gerenu, Gorka; Gómez‑Galán, Marta; Lindskog, Maria; DeFelipe, Javier; Cedazo‑Minguez, Angel; Merino‑Serrais, PaulaAlterations in brain cholesterol homeostasis in midlife are correlated with a higher risk of developing Alzheimer’s disease (AD). However, global cholesterol-lowering therapies have yielded mixed results when it comes to slowing down or preventing cognitive decline in AD. We used the transgenic mouse model Cyp27Tg, with systemically high levels of 27-hydroxycholesterol (27-OH) to examine longterm potentiation (LTP) in the hippocampal CA1 region, combined with dendritic spine reconstruction of CA1 pyramidal neurons to detect morphological and functional synaptic alterations induced by 27-OH high levels. Our results show that elevated 27-OH levels lead to enhanced LTP in the Schafer collateral-CA1 synapses. This increase is correlated with abnormally large dendritic spines in the stratum radiatum. Using immunohistochemistry for synaptopodin (actin-binding protein involved in the recruitment of the spine apparatus), we found a signifcantly higher density of synaptopodinpositive puncta in CA1 in Cyp27Tg mice. We hypothesize that high 27-OH levels alter synaptic potentiation and could lead to dysfunction of fne-tuned processing of information in hippocampal circuits resulting in cognitive impairment. We suggest that these alterations could be detrimental for synaptic function and cognition later in life, representing a potential mechanism by which hypercholesterolemia could lead to alterations in memory function in neurodegenerative diseases.Item Stellate cell computational modeling predicts signal fltering in the molecular layer circuit of cerebellum(Scientific Reports, 2021) Rizza, Martina Francisca; Locatelli, Francesca; Masoli, Stefano; Sánchez‑Ponce, Diana; Muñoz Céspedes, Alberto; Prestori, Francesca; D’Angelo, EgidioThe functional properties of cerebellar stellate cells and the way they regulate molecular layer activity are still unclear. We have measured stellate cells electroresponsiveness and their activation by parallel fber bursts. Stellate cells showed intrinsic pacemaking, along with characteristic responses to depolarization and hyperpolarization, and showed a marked short-term facilitation during repetitive parallel fber transmission. Spikes were emitted after a lag and only at high frequency, making stellate cells to operate as delay-high-pass flters. A detailed computational model summarizing these physiological properties allowed to explore diferent functional confgurations of the parallel fber—stellate cell—Purkinje cell circuit. Simulations showed that, following parallel fber stimulation, Purkinje cells almost linearly increased their response with input frequency, but such an increase was inhibited by stellate cells, which leveled the Purkinje cell gain curve to its 4 Hz value. When reciprocal inhibitory connections between stellate cells were activated, the control of stellate cells over Purkinje cell discharge was maintained only at very high frequencies. These simulations thus predict a new role for stellate cells, which could endow the molecular layer with low-pass and band-pass fltering properties regulating Purkinje cell gain and, along with this, also burst delay and the burst-pause responses pattern.