A5084527843- Neuroscience and Neuropharmacology Research
- Receptor Mechanisms and Signaling
- Neurotransmitter Receptor Influence on Behavior
- Neural dynamics and brain function
- Ion channel regulation and function
- Protein Kinase Regulation and GTPase Signaling
- Retinal Development and Disorders
- Sleep and Wakefulness Research
- Biochemical Analysis and Sensing Techniques
- Neurological disorders and treatments
- Parkinson's Disease Mechanisms and Treatments
- Nicotinic Acetylcholine Receptors Study
- Adipose Tissue and Metabolism
- Circadian rhythm and melatonin
- Neuroinflammation and Neurodegeneration Mechanisms
- Neuroscience and Neural Engineering
- Genetics and Physical Performance
- Single-cell and spatial transcriptomics
- Peroxisome Proliferator-Activated Receptors
- Memory and Neural Mechanisms
- Children's Physical and Motor Development
- Advanced Memory and Neural Computing
- Mitochondrial Function and Pathology
- Biochemical effects in animals
University of Colorado Anschutz Medical Campus
2013-2023
University of Colorado Denver
2010-2022
Brown University
2017-2018
John Brown University
2017
Learning, memory, and cognition are thought to require normal long-term potentiation (LTP) of synaptic strength, which in turn requires binding the Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) NMDA-type glutamate receptor (NMDAR) subunit GluN2B. For LTP induction, many additional required players known. Here we tested hypothesis that CaMKII/GluN2B also mediates more elusive maintenance strength. Intriguingly, CaMKII inhibitor tatCN21 reduces strength only at high concentrations...
Abstract As the primary source of norepinephrine (NE) in brain, locus coeruleus (LC) regulates both arousal and stress responses 1,2 . However, how local neuromodulatory inputs contribute to LC function remains unresolved. Here we identify a network transcriptionally functionally diverse GABAergic neurons dendritic field that integrate distant modulate modes firing control arousal. We define peri-LC anatomy using viral tracing combine single-cell RNA sequencing spatial transcriptomics...
Abstract Ventral tegmental area ( VTA ) dopaminergic neurons are key components of the reward pathway, and their activity is powerfully controlled by a diverse array inhibitory GABA ergic inputs. Two major sources nerve terminals within local interneurons in rostromedial nucleus RMT g). Here, using optogenetics, we compared synaptic properties synapses on dopamine selective activation afferents that originate from these two cell populations. We found little evidence co‐release glutamate...
Abstract Excitatory inputs drive burst firing of locus coeruleus (LC) noradrenaline (NA) neurons in response to a variety stimuli. Though small number glutamatergic LC afferents have been investigated, the overall landscape these excitatory is largely unknown. The current study used an optogenetic approach isolate three afferents: prefrontal cortex (PFC), lateral hypothalamus (LH) and periaqueductal grey (PAG). AAV5‐DIO‐ChR2 was injected into each region male female CaMKII‐Cre mice...
It has proven challenging to faithfully recapitulate the key pathological, physiological, and behavioral features of Parkinson Disease (PD) in animals. Here we used adeno-associated virus (AAV) vectors achieve cell type-specific overexpression wild-type human α-synuclein (αsyn) a fluorophore (mCherry) midbrain dopamine neurons model PD mice. We found that AAVs drove selective expression both αsyn mCherry neurons. In conjunction with approximately 2-fold αsyn, several histopathological...
A hallmark feature of Ca2+/calmodulin (CaM)-dependent protein kinase II (CaMKII) is generation autonomous (Ca2+-independent) activity by T286 autophosphorylation. Biochemical studies have shown that "autonomous" CaMKII ~5-fold further stimulated Ca2+/CaM, but demonstration a physiological function for such regulation within cells has remained elusive. In this study, CaMKII-induced enhancement synaptic strength in rat hippocampal neurons required both and stimulation. Synaptic was decreased...
Stressful experiences potently activate kappa opioid receptors (κORs). κORs in the ventral tegmental area regulate multiple aspects of dopaminergic and non-dopaminergic cell function. Here we show that at GABAergic synapses on rat VTA dopamine neurons, a single exposure to brief cold-water swim stress induces prolonged activation κORs. This is mediated by receptor during stressor followed persistent, ligand-independent constitutive κOR itself. lasting change function not seen neighboring...
The release of acetylcholine from cholinergic interneurons (ChIs) directly modulates striatal output via muscarinic receptors on medium spiny neurons (MSNs). While thalamic inputs provide strong excitatory input to ChIs, cortical primarily regulate MSN firing. Here, we found that, while do drive ChI firing, a subset ChIs responds robustly stimulation as well. To examine how input-evoked changes in firing patterns at synapses onto MSNs, M4-receptor-mediated synaptic events were measured MSNs...
Background Autophosphorylation of the Ca2+/calmodulin (CaM)-dependent protein kinase II (CaMKII) at T286 generates partially Ca2+/CaM-independent "autonomous" activity, which is thought to be required for long-term potentiation (LTP), a form synaptic plasticity underlie learning and memory. A requirement autophosphorylation also efficient Ca2+/CaM-stimulated CaMKII activity has been described, but remains controversial. Methodology/Principal Findings In order determine contribution wild type...
Binding of the Ca²⁺/calmodulin (CaM)-dependent protein kinase II (CaMKII) to NMDA-type glutamate receptor subunit GluN2B is an important control mechanism for regulation synaptic strength. CaMKII binding and translocation synapses are induced by initial Ca²⁺/CaM stimulus, which also activates kinase. Indeed, several mechanistically different inhibitors [tatCN21 KN-93 (N-[2-[[[3-(4-chlorophenyl)-2-propenyl]methylamino]methyl]phenyl]-N-(2-hydroxyethyl)-4-methoxybenzenesulphonamide)]...
The Ca(2+) /calmodulin-dependent protein kinase II (CaMKII) forms 12meric holoenzymes. These holoenzymes cluster into larger aggregates within neurons under ischemic conditions and in vitro when are mimicked. This aggregation is thought to be mediated by interaction between the regulatory domain of one subunit with T-site another a different holoenzyme, an that requires stimulation /CaM nucleotide for its induction. model makes several predictions were verified here: Aggregation was reduced...
This protocol describes motor behavioral assays used to assess function in different models of Parkinson's disease. These include open field, pole, rotarod, cylinder, balance beam tests. It includes an example experimental time course perform identical across two institutions a progressive DA loss model; and the (and its variants) conducted examine partial more complete depletion induced by 6-OHDA (acute model).