- Neuroscience and Neuropharmacology Research
- Neurogenesis and neuroplasticity mechanisms
- Memory and Neural Mechanisms
- Neural dynamics and brain function
- Alzheimer's disease research and treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Genetic and Kidney Cyst Diseases
- Single-cell and spatial transcriptomics
- RNA Research and Splicing
- Epilepsy research and treatment
- Mitochondrial Function and Pathology
- Genetics and Neurodevelopmental Disorders
- Microtubule and mitosis dynamics
- Axon Guidance and Neuronal Signaling
- Neuroscience and Neural Engineering
- Neonatal and fetal brain pathology
- Ion channel regulation and function
- Hedgehog Signaling Pathway Studies
- Glioma Diagnosis and Treatment
- Fetal and Pediatric Neurological Disorders
- Phosphodiesterase function and regulation
- Epigenetics and DNA Methylation
- Functional Brain Connectivity Studies
- Advanced Neuroimaging Techniques and Applications
- MicroRNA in disease regulation
Yale University
2011-2025
University of Chile
2025
Creighton University
2025
University of Florida
2011
Instituto Cajal
1999-2007
Kleijnen Systematic Reviews (United Kingdom)
2007
Consejo Superior de Investigaciones Científicas
2001-2002
Dendritic spines are critical elements of cortical circuits, since they establish most excitatory synapses. Recent studies have reported correlations between morphological and functional parameters spines. Specifically, the spine head volume is correlated with area postsynaptic density (PSD), number receptors ready-releasable pool transmitter, whereas length neck proportional to degree biochemical electrical isolation from its parent dendrite. Therefore, morphology a could determine synaptic...
Primary cilia are present on mammalian neurons and glia, but their function is largely unknown. We generated conditional homozygous mutant mice for a gene we termed Stumpy. Mutants lack have conspicuous abnormalities in postnatally developing brain regions, including hypoplasic hippocampus characterized by primary deficiency neural stem cells known as astrocyte-like precursors (ALNPs). Previous studies suggested that mediate sonic hedgehog (Shh) signaling. Here, find loss of ALNP leads to...
The hippocampal-entorhinal system supports cognitive functions, has lifelong neurogenic capabilities in many species, and is selectively vulnerable to Alzheimer's disease. To investigate potential cellular diversity, we profiled single-nucleus transcriptomes five subregions humans, macaques, pigs. Integrated cross-species analysis revealed robust transcriptomic histologic signatures of neurogenesis the adult mouse, pig, macaque but not humans. Doublecortin (DCX), a widely accepted marker...
Recent results have demonstrated the existence of bidirectional communication between glial cells and neurons. We investigated in brain slices whether rat hippocampal astrocytes respond to acetylcholine synaptically released by an extrinsic pathway. stimulated stratum oriens/alveus, which contains cholinergic afferents from septum diagonal band Broca, recorded whole-cell membrane currents intracellular Ca 2+ levels located oriens. Nerve-fiber stimulation evoked a long-lasting inward current...
Thalamocortical neurons innervating the barrel cortex in neonatal rodents transiently store serotonin (5-HT) synaptic vesicles by expressing plasma membrane transporter (5-HTT) and vesicular monoamine (VMAT2). 5-HTT knock-out (ko) mice reveal a nearly complete absence of 5-HT cerebral immunohistochemistry, barrels, both at P7 adulthood. Quantitative electron microscopy reveals that ko affects neither density synapses nor length contacts layer IV. VMAT2 mice, completely lacking...
Impairment of GABA‐mediated inhibition is one the main hypotheses invoked to explain seizure activity, both in experimental models and human epilepsy. We have studied distribution neurochemical characteristics certain GABAergic circuits normal epileptic sclerotic hippocampal formation. focused our attention mainly on chandelier cells because, together with basket cells, they are considered powerful effects spike generation. Chandelier represent a unique type interneuron whose axon terminals...
Significance The formation of cortical convolutions primates, including humans, is one the most important subjects in developmental neuroscience, but underlying mechanisms—considered mostly solved toward end 20th century—have become controversial last decade. Recent studies suggest that a stem cell zone called outer subventricular (oSVZ) induces gyri to form directly through neurogenesis. Here, we provide evidence macaque monkey demonstrating oSVZ neurogenesis actually complete before...
During early telencephalic development, intricate processes of regional patterning and neural stem cell (NSC) fate specification take place. However, our understanding these in primates, including both conserved species-specific features, remains limited. Here, we profiled 761,529 single-cell transcriptomes from multiple regions the prenatal macaque telencephalon. We deciphered molecular programs organizing centers their cross-talk with NSCs, revealing primate-biased galanin-like peptide (...
It is surprising that after more than a century using rodents for scientific research, there are no clear, consensual, or consistent definitions when mouse rat becomes adult. Specifically, in the field of adult hippocampal neurogenesis, where this concept central, trend to consider puberty marks start adulthood and not uncommon find 30-day-old mice being described as adults. However, others discussed earlier, implies an important bias perceived importance trait because functional studies...
Abstract INTRODUCTION Tau phosphorylated at threonine‐217 (pT217‐tau) is a novel fluid‐based biomarker that predicts onset of Alzheimer's disease (AD) symptoms, but little known about how pT217‐tau arises in the brain, as soluble dephosphorylated post mortem humans. METHODS We used multilabel immunofluorescence and immunoelectron microscopy to examine subcellular localization early‐stage entorhinal prefrontal cortices aged macaques with naturally occurring tau pathology assayed levels...
Importance The risk of mental disorders is consistently associated with variants in CACNA1C (L-type calcium channel Cav1.2) but it not known why these channels are critical to cognition, and whether they affect the layer III pyramidal cells dorsolateral prefrontal cortex that especially vulnerable cognitive disorders. Objective To examine molecular mechanisms expressed primate cortices. Design, Setting, Participants design included transcriptomic analyses from human macaque cortex,...
Neuronal primary cilia are not generally recognized, but they considered to extend from most, if all, neurons in the neocortex. However, when and how develop known. This study used immunohistochemistry for adenylyl cyclase III (ACIII), a marker of cilia, electron microscopic analysis describe development maturation mouse neocortical neurons. Our results indicate that ciliogenesis is initiated late fetal stages after neuroblast migration, mother centriole docks with plasma membrane, becomes...
Abstract Various mechanisms are thought to control excitation of pyramidal cells the cerebral cortex. With immunocytochemical methods, we found that proximal portions numerous cell axons (Pyr‐axons) in human and monkey neocortex immunoreactive for serotonin (5‐HT) receptor 5‐HT‐ 1A . double‐labeling experiments confocal laser microscopy, most (93.4%) 5‐HT –immunoreactive Pyr‐axons present layers II III were innervated by parvalbumin‐immunoreactive chandelier axon terminals. In addition,...
The convolutions of the mammalian cerebral cortex allow enlargement its surface and addition novel functional areas during evolution while minimizing expansion cranium. Cognitive neurodevelopmental disorders in humans, including microcephaly lissencephaly, are often associated with impaired gyrification. In classical model gyrification, area is initially set by number radial units, forces driving cortical folding include neuronal growth, formation neuropil, glial cell intercalation,...
Glutamate carboxypeptidase-II (GCPII) expression in brain is increased by inflammation, e.g. COVID19 infection, where it reduces NAAG stimulation of metabotropic glutamate receptor type 3 (mGluR3). GCPII-mGluR3 signaling increasingly linked to higher cognition, as genetic alterations that weaken mGluR3 or increase GCPII are associated with impaired cognition humans. Recent evidence from macaque dorsolateral prefrontal cortex (dlPFC) shows expressed on dendritic spines, they regulate cAMP-PKA...
Summary: Purpose: Alzheimer disease (AD) and epilepsy are brain disorders frequently associated with neuronal cell loss in mesial temporal lobe structures, but presenting different patterns of damage. Recently it was proposed that a causal relation may exist between AD pathology the appearance some cases AD. This study aimed to determine CA1 hippocampal region from patients bearing presenilin‐1 [E280A] mutation (PS1[E280A]) seizures. Methods: Coronal sections formation (anterior one third)...
Noradrenergic (NE) α1-adrenoceptors (α1-ARs) contribute to arousal mechanisms and play an important role in therapeutic medications such as those for the treatment of posttraumatic stress disorder (PTSD). However, little is known about how α1-AR stimulation influences neuronal firing dorsolateral prefrontal cortex (dlPFC), a newly evolved region that dysfunctional PTSD other mental illnesses. The current study examined effects manipulation on dlPFC rhesus monkeys performing visuospatial...