Publications (9) View all
-
Article: Toward molecular genetic dissection of neural circuits for emotional and motivational behaviors.
[show abstract] [hide abstract]
ABSTRACT: How does the brain process the emotional meaning of sensory stimuli and in turn drive behavior?Studies in the mammalian systems have identified various brain regions and neurotransmitter systems that are critical for emotional and motivational behaviors and have implicated their involvement in neuropsychiatric disorders including anxiety, depression, schizophrenia, and addiction. Despite these significant advancements, the precise neural circuitry underlying emotional and motivational behaviors remains to be understood at molecular and cellular levels. In this review, we discuss how the vertebrate model organism zebrafish can help us gain insights into the underlying circuitry. We first describe studies of several simple and relevant preference behaviors in this model organism, and then discuss approaches and technologies that can be used to uncover the development and function of neural circuits underlying these behaviors.Developmental Neurobiology 06/2011; 72(3):358-65. · 3.55 Impact Factor -
Article: Conditioned place preference behavior in zebrafish.
[show abstract] [hide abstract]
ABSTRACT: This protocol describes conditioned place preference (CPP) in zebrafish following a single exposure to a substance. In the CPP paradigm, animals show a preference for an environment that has previously been associated with a substance (drug), thus indicating the positive-reinforcing qualities of that substance. The test tank consists of two visually distinct compartments separated by a central alley. The protocol involves three steps: the determination of initial preference, one conditioning session and the determination of final preference. This procedure is carried out in ∼2 d; other reported CPP protocols take up to 2 weeks. An increase in preference for the drug-associated compartment is observed after a single exposure. Establishment of this high-throughput protocol in zebrafish makes it possible to investigate the molecular and cellular basis of choice behavior, reward and associative learning. The protocol is also a tool for testing psychoactive compounds in the context of a vertebrate brain.Nature Protocol 02/2011; 6(3):338-45. · 8.36 Impact Factor -
Article: Identification of a brain center whose activity discriminates a choice behavior in zebrafish.
[show abstract] [hide abstract]
ABSTRACT: The ability to make choices and carry out appropriate actions is critical for individual survival and well-being. Choice behaviors, from hard-wired to experience-dependent, have been observed across the animal kingdom. Although differential engagement of sensory neuronal pathways is a known mechanism, neurobiological substrates in the brain that underlie choice making downstream of sensory perception are not well understood. Here, we report a behavioral paradigm in zebrafish in which a half-light/half-dark visual image evokes an innate choice behavior, light avoidance. Neuronal activity mapping using the immediate early gene c-fos reveals the engagement of distinct brain regions, including the medial zone of the dorsal telencephalic region (Dm) and the dorsal nucleus of the ventral telencephalic area (Vd), the teleost anatomical homologs of the mammalian amygdala and striatum, respectively. In animals that were subjected to the identical sensory stimulus but displayed little or no avoidance, strikingly, the Dm and Vd were not engaged, despite similar levels of activation in the brain nuclei involved in visual processing. Based on these findings and previous connectivity data, we propose a neural circuitry model in which the Dm serves as a brain center, the activity of which predicates this choice behavior in zebrafish.Proceedings of the National Academy of Sciences 02/2011; 108(6):2581-6. · 9.68 Impact Factor -
Article: Corticotropin-releasing factor critical for zebrafish camouflage behavior is regulated by light and sensitive to ethanol.
[show abstract] [hide abstract]
ABSTRACT: The zebrafish camouflage response is an innate "hard-wired" behavior that offers an excellent opportunity to explore neural circuit assembly and function. Moreover, the camouflage response is sensitive to ethanol, making it a tractable system for understanding how ethanol influences neural circuit development and function. Here we report the identification of corticotropin-releasing factor (CRF) as a critical component of the camouflage response pathway. We further show that ethanol, having no direct effect on the visual sensory system or the melanocytes, acts downstream of retinal ganglion cells and requires the CRF-proopiomelanocortin pathway to exert its effect on camouflage. Treatment with ethanol, as well as alteration of light exposure that changes sensory input into the camouflage circuit, robustly modifies CRF expression in subsets of neurons. Activity of both adenylyl cyclase 5 and extracellular signal-regulated kinase (ERK) is required for such ethanol-induced or light-induced plasticity of crf expression. These results reveal an essential role of a peptidergic pathway in camouflage that is regulated by light and influenced by ethanol at concentrations relevant to abuse and anxiolysis, in a cAMP-dependent and ERK-dependent manner. We conclude that this ethanol-modulated camouflage response represents a novel and relevant system for molecular genetic dissection of a neural circuit that is regulated by light and sensitive to ethanol.Journal of Neuroscience 01/2011; 31(1):214-24. · 7.11 Impact Factor -
Article: Differences of acute versus chronic ethanol exposure on anxiety-like behavioral responses in zebrafish.
[show abstract] [hide abstract]
ABSTRACT: Zebrafish, a vertebrate model organism amenable to high throughput screening, is an attractive system to model and study the mechanisms underlying human diseases. Alcoholism and alcoholic medical disorders are among the most debilitating diseases, yet the mechanisms by which ethanol inflicts the disease states are not well understood. In recent years zebrafish behavior assays have been used to study learning and memory, fear and anxiety, and social behavior. It is important to characterize the effects of ethanol on zebrafish behavioral repertoires in order to successfully harvest the strength of zebrafish for alcohol research. One prominent effect of alcohol in humans is its effect on anxiety, with acute intermediate doses relieving anxiety and withdrawal from chronic exposure increasing anxiety, both of which have significant contributions to alcohol dependence. In this study, we assess the effects of both acute and chronic ethanol exposure on anxiety-like behaviors in zebrafish, using two behavioral paradigms, the Novel Tank Diving Test and the Light/Dark Choice Assay. Acute ethanol exposure exerted significant dose-dependent anxiolytic effects. However, withdrawal from repeated intermittent ethanol exposure disabled recovery from heightened anxiety. These results demonstrate that zebrafish exhibit different anxiety-like behavioral responses to acute and chronic ethanol exposure, which are remarkably similar to these effects of alcohol in humans. Because of the accessibility of zebrafish to high throughput screening, our results suggest that genes and small molecules identified in zebrafish will be of relevance to understand how acute versus chronic alcohol exposure have opposing effects on the state of anxiety in humans.Behavioural brain research 01/2011; 219(2):234-9. · 3.22 Impact Factor
