Abstract
The behavioral effects of ethanol have been studied in multiple animal models including zebrafish. Locomotion of zebrafish larvae is resistant to high concentrations of ethanol in bath solution. This resistance has been attributed to a lower systemic concentration of ethanol in zebrafish when compared with bath solution, although the mechanism to maintain such a steep gradient is unclear. Here we examined whether the intrinsic properties of neurons play roles in this resistance. In order to minimize the contribution of metabolism and diffusional barriers, larvae were hemisected and the anterior half immersed in a range of ethanol concentrations thereby ensuring the free access of bath ethanol to the brain. The response to vibrational stimuli of three types of reticulospinal neurons: Mauthner neurons, vestibulospinal neurons, and MiD3 neurons were examined using an intracellular calcium indicator. The intracellular [Ca2+] response in MiD3 neurons decreased in 100 mM ethanol, while Mauthner neurons and vestibulospinal neurons required >300 mM ethanol to elicit similar effects. The ethanol effect in Mauthner neurons was reversible following removal of ethanol. Interestingly, activities of MiD3 neurons displayed spontaneous recovery in 300 mM ethanol, suggestive of acute tolerance. Finally, we examined with mechanical vibration the startle response of free-swimming larvae in 300 mM ethanol. Ethanol treatment abolished long latency startle responses, suggesting a functional change in neural processing. These data support the hypothesis that individual neurons in larval zebrafish brains have distinct patterns of response to ethanol dictated by specific molecular targets.
Highlights
Alcoholism is a severe disease affecting approximately 18 million people in the United States [1]
In this study we examined the intrinsic properties of neurons in zebrafish larvae exposed to high doses of ethanol in a semi-intact preparation
Comparison of the neural activity in sectioned and intact larvae suggest that the ratio of internal/external ethanol concentration in 5–6 dpf zebrafish larvae may be close to 1
Summary
Alcoholism is a severe disease affecting approximately 18 million people in the United States [1]. Alcohol induces a variety of effects on the central nervous system, and acute administration of ethanol in humans induces euphoria, sedation and hypothermia [2]. Various animal models have been utilized to clarify the mechanisms of ethanol induced-changes in the CNS. Zebrafish genes are 70–80% identical to human orthologs [4]. Their CNS possesses classical vertebrate architecture and a full complement of neurotransmitters [5,6]. Thanks to these similarities, zebrafish are being increasingly utilized as a model in behavioral pharmacology
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