TopicNeuroscience

knockout mice

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24Total items

22ePosters

2Seminars

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SeminarNeuroscience

Towards Human Systems Biology of Sleep/Wake Cycles: Phosphorylation Hypothesis of Sleep

Hiroki R. Ueda

Graduate School of Medicine, University of Tokyo

Jan 15, 2024

The field of human biology faces three major technological challenges. Firstly, the causation problem is difficult to address in humans compared to model animals. Secondly, the complexity problem arises due to the lack of a comprehensive cell atlas for the human body, despite its cellular composition. Lastly, the heterogeneity problem arises from significant variations in both genetic and environmental factors among individuals. To tackle these challenges, we have developed innovative approaches. These include 1) mammalian next-generation genetics, such as Triple CRISPR for knockout (KO) mice and ES mice for knock-in (KI) mice, which enables causation studies without traditional breeding methods; 2) whole-body/brain cell profiling techniques, such as CUBIC, to unravel the complexity of cellular composition; and 3) accurate and user-friendly technologies for measuring sleep and awake states, exemplified by ACCEL, to facilitate the monitoring of fundamental brain states in real-world settings and thus address heterogeneity in human.

SeminarNeuroscienceRecording

The GluN2A Subunit of the NMDA Receptor and Parvalbumin Interneurons: A Possible Role in Interneuron Development

Steve Traynelis & Chad Camp

Emory University School of Medicine

Jan 19, 2022

N-methyl-D-aspartate receptors (NMDARs) are excitatory glutamate-gated ion channels that are expressed throughout the central nervous system. NMDARs mediate calcium entry into cells, and are involved in a host of neurological functions. The GluN2A subunit, encoded by the GRIN2A gene, is expressed by both excitatory and inhibitory neurons, with well described roles in pyramidal cells. By using Grin2a knockout mice, we show that the loss of GluN2A signaling impacts parvalbumin-positive (PV) GABAergic interneuron function in hippocampus. Grin2a knockout mice have 33% more PV cells in CA1 compared to wild type but similar cholecystokinin-positive cell density. Immunohistochemistry and electrophysiological recordings show that excess PV cells do eventually incorporate into the hippocampal network and participate in phasic inhibition. Although the morphology of Grin2a knockout PV cells is unaffected, excitability and action-potential firing properties show age-dependent alterations. Preadolescent (P20-25) PV cells have an increased input resistance, longer membrane time constant, longer action-potential half-width, a lower current threshold for depolarization-induced block of action-potential firing, and a decrease in peak action-potential firing rate. Each of these measures are corrected in adulthood, reaching wild type levels, suggesting a potential delay of electrophysiological maturation. The circuit and behavioral implications of this age-dependent PV interneuron malfunction are unknown. However, neonatal Grin2a knockout mice are more susceptible to lipopolysaccharide and febrile-induced seizures, consistent with a critical role for early GluN2A signaling in development and maintenance of excitatory-inhibitory balance. These results could provide insights into how loss-of-function GRIN2A human variants generate an epileptic phenotypes.

knockout mice

Latest

Towards Human Systems Biology of Sleep/Wake Cycles: Phosphorylation Hypothesis of Sleep

The GluN2A Subunit of the NMDA Receptor and Parvalbumin Interneurons: A Possible Role in Interneuron Development

LONGITUDINAL BEHAVIORAL PROFILING OF MNK1 AND NLGN3 KNOCKOUT MICE USING AUTOMATED HOME-CAGE TRACKING

SENSORY FUNCTIONS OF THE Β-SECRETASE BACE1 IN KNOCKOUT MICE

ROLE OF SPINAL DORSAL HORN BEGAIN IN NEUROPATHIC AND INFLAMMATORY PAIN: INSIGHTS FROM CONDITIONAL KNOCKOUT MICE

PRESERVED STRIATAL NEURONS DESPITE IMPAIRED OXPHOS IN ARGINASE 2 KNOCKOUT MICE. PROTECTION VIA METABOLIC REPROGRAMMING?

BEHAVIORAL CHARACTERIZATION OF AGED <EM>FMR1 </EM>KNOCKOUT MICE. BASAL PHENOTYPING AND SKF81297-MEDIATED DOPAMINERGIC D1/D5 RECEPTOR MODULATION IN AGED FRAGILE X SYNDROME MOUSE MODEL

OLFACTORY BEHAVIORS AND RESPONSES IN FOREBRAIN-SPECIFIC <EM>CCN2</EM> KNOCKOUT MICE

INTEGRATED BULK MRNA-SEQ AND SYNAPTIC PROTEOMIC PROFILING OF VULNERABLE BRAIN REGIONS IN TDP-43 CONDITIONAL KNOCKOUT MICE

MAPPING SEX‑SPECIFIC SENSORY–PSYCHOMOTOR DYSREGULATION IN A NEURONAL GROWTH REGULATOR 1 (NEGR1) KNOCKOUT MICE

INVOLVEMENT OF THE CANNABINOID SYSTEM IN STRESS-INDUCED REINSTATEMENT TO OPIOID USE: A STUDY IN CB1 KNOCKOUT MICE OF BOTH SEXES

Orexin knockout mice have compromised orientation discrimination and display reduced AMPAR-mediated excitation in L4-2/3 connections in the primary visual cortex

Mood and cognition related analysis in dimethylarginine dimethylaminohydrolase-1 knockout mice

Sex-specific effects in fear memory generalization in IL-6 knockout mice

Synapsin triple knockout mice display social and cognitive deficits coupled to cortical glutamatergic dysfunction

Phenotypic characterization of nociceptin/orphanin FQ receptor knockout mice (NOP(-/-)) in different in vivo models of migraine and evaluation of the NOP receptor as a treatment target

Collagen XVIII knockout mice as a model for early cerebral small vessel disease

Analysis of anxiety-related/social behaviour and neural circuitry abnormalities in ligand of Numb protein X (LNX) knockout mice

Cellular response to oxidative stress and senescence in Fmr1 knockout mice modelling Fragile X Syndrome

Comparative examination of the ventral tegmental area in wild type and pituitary adenylate cyclase-activating polypeptide (PACAP) knockout mice

Deficient ocular dominance plasticity in primary visual cortex of orexin knockout mice

Elevated reactive aggression in forebrain-specific CCN2 knockout mice

Inhibition of glial scar formation after spinal cord injury in Noggin conditional knockout mice and by anti-Noggin antibody treatment

Lipid droplet pathology in the hippocampus of aged wild-type and perilipin2 knockout mice