神经生物学

Glycogen synthase kinase-3 (GSK-3) occupies an unusual niche in cellular regulation via its negative regulation of a series of important cellular target proteins coupled with its own sensitivity to several major signaling pathways including the Wnt, Notch, Hedgehog, and insulin syst ...

The erbB membrane tyrosine kinases (EGF receptor, erbB2, erbB3, and erbB4) are a family of structurally similar transmembrane proteins that act as receptors for the EGF and neuregulin (NRG) families of growth factors. ErbB receptors and their ligands are widely expressed by neurons and glia t ...

Cyclin-dependent kinase 5 (Cdk5) is a versatile protein kinase that plays a role in a variety of neuronal activities including neuronal migration during brain development, synaptic activities in mature neurons, and neuronal cell death in neurodegenerative diseases. However, the fu ...

Larval zebrafish are genetically tractable, easy to manipulate, and can be generated in large numbers. Their small size also makes them ideal for high-throughput screens for genes or pharmacological compounds that affect behavior. Thus, larval zebrafish are an ideal model system to inve ...

The light–dark preference test is one of the most commonly used anxiety models in animal preclinical studies. This test assesses spontaneous/natural tendency of an animal to explore/avoid certain zones of a given environment, for instance a half black-half white box. This test has been vali ...

One of the most commonly used behavioral endpoints measured in preclinical studies employing rodent models is thigmotaxis (or “wall-hugging”). Thigmotaxis is the propensity to avoid the center of an arena and stay or move in close proximity to the boundaries of the environment. Thigmotax ...

The attributes of the zebrafish (Danio rerio) make it an excellent model system for the development and discovery of new drugs. A robust behavioral assay is described that has been used successfully in studies of nicotine biology. The movement response of a group of larval zebrafish is measured o ...

The zebrafish is a promising model organism in vision research. To evaluate the visual function of laboratory animals, reliable behavioral assays are indispensable. The optokinetic response (OKR) assay has proven a valuable tool not only to screen for mutations affecting the visual sys ...

Olfactory responses develop early in larval zebrafish and are important throughout life to direct physiological and behavioral responses. Responses are evoked by odorants, which act as ligands to the olfactory neuron receptors. A response of immediate relevance is the detection of f ...

This protocol describes an assay for measuring visual recognition memory in larval zebrafish using an automated imaging system. Dubbed the “context recognition assay,” this assay measures the responses of larvae to familiar and unfamiliar visual stimuli displayed on an LCD screen be ...

A long-standing debate on whether fish can feel pain is coming to a close as evidence gathers regarding the existence of nociceptive mechanisms in the peripheral and central nervous system of these vertebrates, as well as nocifensive behavior that can be altered by pharmacological treatme ...

The open tank diving test and the light/dark test are commonly used to assess anxiety-like behavior in zebrafish. The open tank test exerts relatively weak control over behavior, and uses vertical locomotion as its primary measure. The light/dark test exerts relatively strong control over b ...

The open field test is a well-established paradigm for assaying anxiety-related behaviors and has been successfully employed in a broad range of species. We describe an adaptation of this test for the zebrafish, which is increasingly widely used as a model for anxiety-related behavior and st ...

Some teleost fish present scototaxis, a tendency to search for dark places and avoid brightly lit spaces. In zebrafish, it has been proposed that scototaxis (preference for dark environments) is a model of anxiety. In this chapter, we discuss some evidence regarding that proposal, and present a s ...

Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase known to merge extracellular instructions with information about cellular metabolic resources and control the rate of anabolic and catabolic processes accordingly. In neurons, mTOR has been implicated in ...

Endocytosis and trafficking of Trk receptors are central to their functions in neuronal development. Neurotrophin binding to Trk receptors induces endocytosis of Trk receptors as a ligand–receptor complex in axon terminals. This endocytic ligand–receptor complex, termed the s ...

Diacylglycerol kinase (DGK) is a lipid kinase but not protein kinase. However, the enzyme regulates many protein kinases including PKC, PI4P-Kinase, and mTOR by reducing the amount of diacylglycerol and producing phosphatidic acid. To date, ten mammalian DGKs have been cloned and divided i ...

The protein kinase C (PKC) family contains ten members that share a catalytic core but differ in the composition of their regulatory modules. The conventional PKCs are a subfamily whose regulatory domains bind to Ca2+ and to the lipid second messenger diacylglycerol and thus they are activated ...

Cyclic-AMP dependent protein kinase (PKA) is present in most branches of the living kingdom, and as an example in the nervous system where PKA integrates the cellular effects of various neuromodulators. The recent development of fluorescence resonance energy transfer (FRET) biosens ...

PTEN-induced novel kinase 1 (PINK1) and leucine-rich repeat kinase 2 (LRRK2) are two protein kinases associated with recessive and dominant forms of parkinsonism, respectively. Mutations in PINK1 cause loss of protein function whereas mutations in LRRK2 are less easily defined but, in s ...