A5052780363- Neuroscience and Neuropharmacology Research
- Memory and Neural Mechanisms
- Receptor Mechanisms and Signaling
- Neuroinflammation and Neurodegeneration Mechanisms
- Photoreceptor and optogenetics research
- Mitochondrial Function and Pathology
- Neural dynamics and brain function
- Neuroendocrine regulation and behavior
- Neuroscience, Education and Cognitive Function
- Zebrafish Biomedical Research Applications
- CRISPR and Genetic Engineering
- Stress Responses and Cortisol
- RNA and protein synthesis mechanisms
- Genetics and Neurodevelopmental Disorders
- Neurotransmitter Receptor Influence on Behavior
- Bacterial Genetics and Biotechnology
- Retinal Development and Disorders
- Neurogenesis and neuroplasticity mechanisms
- Chemical Synthesis and Analysis
- Nicotinic Acetylcholine Receptors Study
- RNA Interference and Gene Delivery
- Memory Processes and Influences
- Spatial Cognition and Navigation
- Alzheimer's disease research and treatments
- Epigenetics and DNA Methylation
Scripps Research Institute
2010-2022
University of California, San Diego
2000-2022
Neurosciences Institute
2016
Vrije Universiteit Amsterdam
2007
Cognitive Research (United States)
2007
Genomics Institute of the Novartis Research Foundation
2000-2004
Salk Institute for Biological Studies
2000
Howard Hughes Medical Institute
1992-1998
New York State Psychiatric Institute
1996-1998
Columbia University
1990-1997
One of the major limitations in use genetically modified mice for studying cognitive functions is lack regional and temporal control gene function. To overcome these limitations, a forebrain-specific promoter was combined with tetracycline transactivator system to achieve both transgene expression. Expression an activated calcium-independent form calcium-calmodulin-dependent kinase II (CaMKII) resulted loss hippocampal long-term potentiation response 10-hertz stimulation deficit spatial...
Using the phage P1–derived Cre/loxP recombination system, we have developed a method to create mice in which deletion (knockout) of virtually any gene interest is restricted subregion or specific cell type brain such as pyramidal cells hippocampal CA1 region. The recombination–based appears require certain level Cre protein expression. subregional knockout should allow more precise analysis impact mutation on animal behaviors.
Do learning and retrieval of a memory activate the same neurons? Does number reactivated neurons correlate with strength? We developed transgenic mouse that enables long-lasting genetic tagging c-fos-active neurons. found in basolateral amygdala are activated during Pavlovian fear conditioning retrieval. The correlated positively behavioral expression memory, indicating stable neural associative memory. ability to manipulate these genetically should allow more precise dissection molecular...
To investigate the function of autophosphorylated form CaMKII in synaptic plasticity, we generated transgenic mice that express a kinase is Ca2+ independent as result point mutation Thr-286 to aspartate, which mimics autophosphorylation. Mice expressing mutant show an increased level Ca(2+)-independent activity similar seen following LTP. The nevertheless exhibit normal LTP response stimulation at 100 Hz. However, lower frequencies, range 1-10 Hz, there systematic shift size and direction...
To determine the genetic causes and molecular mechanisms responsible for neurobehavioral differences in mice, we used highly parallel gene expression profiling to detect genes that are differentially expressed between 129SvEv C57BL/6 mouse strains at baseline response seizure. In addition, identified specific brain regions. We found approximately 1% of least one region seizure is significantly different two inbred strains. The results lead identification may account distinct phenotypes...
A form of learning in the marine mollusk Aplysia , long-term sensitization gill- and siphon-withdrawal reflex, results formation new synaptic connections between presynaptic siphon sensory neurons their target cells. These structural changes can be mimicked, when cells are maintained culture, by application serotonin, an endogenous facilitating neurotransmitter . group cell surface proteins, designated adhesion molecules (apCAM's) was down-regulated response to serotonin. The deduced amino...
Adding Artificial Associations In the mammalian cortex, there is significant spontaneous neural activity that internally generated, rather than arising from sensory inputs, and this influences processing of natural stimuli. What role does generated play in forming accessing new memory representations? Using transgenic mice combined with controlled artificial activation widely distributed neuronal ensembles associated specific contexts, Garner et al. (p. 1513 ; see Perspective by Morris...
Synaptic inputs on dendrites are nonlinearly converted to action potential outputs, yet the spatiotemporal patterns of dendritic activation remain be elucidated at single-synapse resolution. In rodents, we optically imaged synaptic activities from hundreds spines in hippocampal and neocortical pyramidal neurons ex vivo vivo. Adjacent were frequently synchronized spontaneously active networks, thereby forming foci that received locally convergent presynaptic cell assemblies. This precise...
The stabilization of long-term memories requires de novo protein synthesis. How can proteins, synthesized in the soma, act on specific synapses that participate a given memory? We studied dynamics newly AMPA-type glutamate receptors (AMPARs) induced with learning using transgenic mice expressing GluR1 subunit fused to green fluorescent (GFP-GluR1) under control c-fos promoter. found learning-associated recruitment GFP-GluR1 selectively mushroom-type spines adult hippocampal CA1 neurons 24...
To investigate the roles phosphatases play in hippocampal-dependent memory, we studied transgenic mice overexpressing a truncated form of calcineurin. These have normal short-term memory but defective long-term evident on both spatial task and visual recognition task, providing genetic evidence for role rodent hippocampus nonspatial memory. The defect could be fully rescued by increasing number training trials, suggesting that capacity We next analyzed calcineurin regulated manner found is...
Neuronal signaling requires that synaptic proteins be appropriately localized within the cell and regulated there. In mammalian neurons, polyribosomes are found not just in body, but also dendrites where they concentrated or beneath dendritic spine. The α subunit of Ca 2+ -calmodulin-dependent protein kinase II (CaMKIIα) is one only five mRNAs known to present dendrites, as well soma neurons. This targeted subcellular localization mRNA for CaMKIIα provides a possible biological mechanism...
To obtain rapidly inducible and reversible expression of transgenes in the forebrain mouse, we have combined reverse tetracycline-controlled transactivator (rtTA) system with CaMKIIalpha promoter. We show that doxycycline induces maximal gene neurons within 6 days this can be reversed by removal doxycycline. Using calcineurin as a test transgene, doxycycline-induced impairs both an intermediate form LTP (I-LTP) hippocampus storage spatial memory. The reversibility rtTA turn allowed us to...
To relate different forms of synaptic plasticity to the formation and maintenance place cells in hippocampus, we have recorded freely behaving, transgenic mice that express a mutated Ca2+-independent form CaM Kinase II. These normal long-term potentiation (LTP) at 100 Hz, but they lack LTP response stimulation 5–10 Hz are impaired on spatial memory tasks. In these mice, CA1 region three important differences from those wild types: less common, precise, stable. findings suggest range may be...
Neuregulin-1 (NRG1) and its ErbB2/B4 receptors are encoded by candidate susceptibility genes for schizophrenia, yet the essential functions of NRG1 signaling in CNS still unclear. Using CRE/LOX technology, we have inactivated ErbB2/B4-mediated specifically CNS. In contrast to expectations, cell layers cerebral cortex, hippocampus, cerebellum develop normally mutant mice. Instead, loss impairs dendritic spine maturation perturbs interactions postsynaptic scaffold proteins with glutamate...
To examine the physiological role of Fyn tyrosine kinase in neurons, we generated transgenic mice that expressed a fyn cDNA under control calcium/calmodulin-dependent protein IIα promoter. With this promoter, detected only low expression neonatal brain. In contrast, there was strong fyn-transgene neurons adult forebrain. determine whether impairment long-term potentiation (LTP) observed fyn-deficient caused directly by lack hippocampal or indirectly an neuronal development, fyn-rescue...
The hippocampus is critical for episodic memory and computational studies have predicted specific functions each hippocampal subregion. Particularly, the dentate gyrus (DG) hypothesized to perform pattern separation by forming distinct representations of similar inputs. How achieved DG remains largely unclear. By examining neuronal activities at a population level, we revealed that, unlike CA1 neuron populations, granule cell (DGC) ensembles activated learning were not preferentially...