Jose Martínez-Hernández

Clinatec

Plaques of amyloid-β (Aβ) and neurofibrillary tangles are the main pathological characteristics of Alzheimer’s disease (AD). However, some older adult people with AD can retain cognitive function. Unraveling the factors that lead to this cognitive resilience to AD offers promising prospects for identifying new therapeutic targets. Our hypothesis fo...

Microtubules (MTs) support a variety of neuronal functions, such as maintenance of cell structure, transport, and synaptic plasticity. Neuronal MTs are highly heterogeneous due to several tubulin isotypes and the presence of multiple post-translational modifications, such as detyrosination and acetylation. The tubulin tyrosination/detyrosination cy...

In chemical synapses undergoing high frequency stimulation, vesicle components can be retrieved from the plasma membrane via a clathrin-independent process called activity-dependent bulk endocytosis (ADBE). Alix (ALG-2-interacting protein X/PDCD6IP) is an adaptor protein binding to ESCRT and endophilin-A proteins which is required for clathrin-inde...

Microtubules play fundamental roles in the maintenance of neuronal processes and in synaptic function and plasticity. While dynamic microtubules are mainly composed of tyrosinated tubulin, long-lived microtubules contain detyrosinated tubulin, suggesting that the tubulin tyrosination/detyrosination cycle is a key player in the maintenance of microt...

In neurons, dynamic microtubules play regulatory roles in neurotransmission and synaptic plasticity. While stable microtubules contain detyrosinated tubulin, dynamic microtubules are composed of tyrosinated tubulin, suggesting that the tubulin tyrosination/detyrosination (Tyr/deTyr) cycle modulates microtubule dynamics and synaptic function. In the...

In chemical synapses undergoing high frequency stimulation, vesicle components can be retrieved from the plasma membrane via a clathrin-independent process called activity dependent bulk endocytosis (ADBE). Alix (ALG-2 interacting protein X)/ PDCD6IP) is an adaptor protein binding to ESCRT and endophilin-A proteins and thereby driving deformation a...

Alterations of excitatory synaptic function are the strongest correlate to the pathological disturbance of cognitive ability observed in the early stages of Alzheimer disease (AD). This pathological feature is driven by Amyloid-β oligomers (Aβo) and propagates from neuron to neuron. Here, we investigated the mechanism by which Aβo affect the functi...

Metabotropic γ-aminobutyric acid (GABAB) receptors contribute to the control of network activity and information processing in hippocampal circuits by regulating neuronal excitability and synaptic transmission. The dysfunction in the dentate gyrus (DG) has been implicated in Alzheimer´s disease (AD). Given the involvement of GABAB receptors in AD,...

Three-dimensional microscopy is mandatory for biological investigation. We describe a stimulated emission depletion selective plane illumination microscope (STED-SPIM) that provides both ease of implementation and an efficient optical slicing. This self-aligned system is based on a single diode-pumped solid-state laser and phase masks made of simpl...

The hippocampus plays key roles in learning and memory and is a main target of Alzheimer’s disease (AD), which causes progressive memory impairments. Despite numerous investigations about the processes required for normal hippocampal functions, the neurotransmitter receptors involved in synaptic deficits by which AD disables the hippocampus are not...

Phosphatase and tensin homolog on chromosome 10 (PTEN) is a tumor suppressor and autism-associated gene that exerts an important influence over neuronal structure and function during development. In addition, it participates in synaptic plasticity processes in adulthood. As an attempt to assess synaptic and developmental mechanisms by which PTEN ca...

Amyloid-β (A β) drives the synaptic impairment and dendritic spine loss characteristic of Alzheimer’s disease (AD), but how Aβ affects the actin cytoskeleton remains unknown and contentious. The actin-binding protein, cofilin-1 (cof1), is a major regulator of actin dynamics in dendritic spines, and is subject to phospho-regulation by multiple pathw...

Emerging evidence indicates that microtubule-associated proteins (MAPs) are implicated in synaptic function; in particular, mice deficient for MAP6 exhibit striking deficits in plasticity and cognition. How MAP6 connects to plasticity mechanisms is unclear. Here, we address the possible role of this protein in dendritic spines. We find that in MAP6...

Angelman syndrome is a complex neurodevelopmental disorder caused by the lack of function in the brain of a single gene, UBE3A. The E3 ligase coded by this gene is known to build K48-linked ubiquitin chains, a modification historically considered to target substrates for degradation by the proteasome. However, a change in protein abundance is not p...

The rodent hippocampus supports non-spatial object memory. Serotonin 5-HT2A receptors (5-HT2AR) are widely expressed throughout the hippocampus. We previously demonstrated that the activation of 5-HT2ARs enhanced the strength of object memory assessed 24 h after a limited (i.e., weak memory) training procedure. Here, we examined the subcellular dis...

During development of the central nervous system, anosmin-1 (A1) works as a chemotropic cue contributing to axonal outgrowth and collateralization, as well as modulating the migration of different cell types, fibroblast growth factor receptor 1 (FGFR1) being the main receptor involved in all these events. To further understand the role of A1 during...

The charged multivesicular body proteins (Chmp1-7) are an evolutionarily conserved family of cytosolic proteins that transiently assembles into helical polymers that change the curvature of cellular membrane domains. Mutations in human CHMP2B cause frontotemporal dementia, suggesting that this protein may normally control some neuron-specific proce...

Small-conductance, Ca2+-activated K+ (SK) channels regulate neuronal excitability in a variety of ways. To understand their roles in different neuronal subtypes it is important to determine their precise subcellular distribution. Here, we used biochemical, light microscopy immunohistochemical and immunoelectron microscopy techniques, combined with...

The interior of the neuronal cell nucleus is a highly organized three-dimensional (3D) structure where regions of the genome that are linearly millions of bases apart establish sub-structures with specialized functions. To investigate neuronal chromatin organization and dynamics in vivo, we generated bitransgenic mice expressing GFP-tagged histone...

Key points The molecular basis of left–right asymmetries in brain structure and function is a central question in neuroscience. We have previously demonstrated that the neuronal circuitry composed of hippocampal pyramidal neurones is asymmetrical depending on the hemispheric origin of presynaptic inputs and cell polarity of the postsynaptic neurone...

Huntington's disease is caused by an expanded polyglutamine repeat in the huntingtin protein (HTT), but the pathophysiological sequence of events that trigger synaptic failure and neuronal loss are not fully understood. Alterations in N-methyl-D-aspartate (NMDA)-type glutamate receptors (NMDARs) have been implicated. Yet, it remains unclear how the...

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are subthreshold activated voltage-gated ion channels. In the cortex, these channels are predominantly expressed in dendrites where they significantly modify dendritic intrinsic excitability as well synaptic potential shapes and integration. HCN channel trafficking to dendrites is r...

Voltage-gated sodium channels are responsible for action potential initiation and propagation in electrically excitable cells. In this study, we used biochemical, immunohistochemical and quantitative immunoelectron microscopy techniques to reveal the temporal and spatial expression of the Na(v)1.2 channel subunit in granule cells of cerebellum. Usi...

Psychostimulants induce neuroadaptations in excitatory and fast inhibitory transmission in the ventral tegmental area (VTA). Mechanisms underlying drug-evoked synaptic plasticity of slow inhibitory transmission mediated by GABA(B) receptors and G protein-gated inwardly rectifying potassium (GIRK/Kir(3)) channels, however, are poorly understood. Her...

Male sexual pheromones are rewarding stimuli for female mice, able to induce conditioned place preference. To test whether processing these natural reinforcing stimuli depends on the dopaminergic innervation of the nucleus accumbens, as for other natural rewards, we compare the effects of specific lesions of the dopaminergic innervation of the medi...

J. Neurochem. (2012) 120, 259–268. Autophagy is an important process which plays a key role in cellular homeostasis by degrading cytoplasmic components in the lysosomes, which facilitates recycling. Alterations to normal autophagy have been linked to excitotoxicity, but the mechanisms governing its signal transduction remain unclear. The aim of thi...

In rodents, sexual advertisement and gender recognition are mostly (if not exclusively) mediated by chemosignals. Specifically, there is ample evidence indicating that female mice are 'innately' attracted by male sexual pheromones that have critical non-volatile components and are detected by the vomeronasal organ. These pheromones can only get acc...

The amygdala of all tetrapod vertebrates receives direct projections from the main and accessory olfactory bulbs, and the strong similarities in the organization of these projections suggest that they have undergone a very conservative evolution. However, current ideas about the function of the amygdala do not pay sufficient attention to its chemos...

Even in rodents, there is no clear evidence of the existence of sexual pheromones mediating instinctive intersexual attraction. In this review we discuss previous results of our group indicating that female mice reared in the absence of male-derived chemosignals are ‘attracted’ by some components of male-soiled bedding, presumably detected by the v...

The role of the meso-accumbens dopaminergic pathway in reward-related behaviours is the subject of intense investigation. In this regard, here we analyse the effects of specific lesions of dopaminergic cells of the ventral tegmental area (VTA) of female mice on two goal-directed behaviours, namely sucrose preference (intake of sucrose solution vs....