Modulatory Neurotransmitter Systems and Behavior: Towards Zebrafish Models of Neurodegenerative Diseases

Abstract

The modulatory aminergic neurotransmitters are involved in practically all important physiological systems in the brain, and many of them are also involved in human central nervous system diseases, including Parkinson's disease, schizophrenia, Alzheimer's disease, and depression. The zebrafish brain aminergic systems share many structural properties with the mammalian systems. The noradrenergic, serotonergic, and histaminergic systems are highly similar. The dopaminergic systems also show similarities with the major difference being the lack of dopaminergic neurons in zebrafish mesencephalon. Development of automated quantitative behavioral analysis methods for zebrafish and imaging systems of complete brain neurotransmitter networks have enabled comprehensive studies on these systems in normal and pathological conditions. It is possible to visualize complete neurotransmitter systems in the whole zebrafish brain at an age when the fish already displays all major vital behaviors except reproduction. Alterations of brain dopaminergic systems with MPTP, the neurotoxin that in humans and rodents induces Parkinson's disease, induces both changes in zebrafish dopaminergic system and quantifiable abnormalities in motor behavior. Chemically-induced brain histamine deficiency causes an identifiable alteration in histaminergic neurons and terminal networks, and a clear change in swimming behavior and long-term memory. Combining the imaging techniques and behavioral methods with zebrafish genetics is likely to help reveal how the modulatory transmitter systems interact to produce important behaviors, and how they are regulated in pathophysiological conditions and diseases.

Discrimination reversal and attentional sets in zebrafish (Danio rerio)

“…For example, using tyrosine hydroxylase (TH) immunocytochemistry, Rink and Wullimann [29] described the ascending dopaminergic pathways in the zebrafish brain, speculating homologies for the ventral tegmental area (posterior tuberculum), the striatum (ventralis telencephali) and prefrontal cortex (pallium or dorsomedial telencephalon). Ascertaining the functional relevance of these hodological and anatomical similarities, however, relies heavily on development of valid and reliable behavioural assays in the zebrafish, combined with lesion studies and/or use of the extensively available mutant lines [30].…”

Amigo Adhesion Protein Regulates Development of Neural Circuits in Zebrafish Brain

“…First, the locomotor activity of 6-dpf larvae was observed during 10 min in 24-well plates as described previously (20,22). The analysis included 80 fish (20/group in four independent experiments).…”

Zebrafish, a Potential Novel Research Tool for the Analysis and Modeling of Anxiety

“…It is notable that evolutionary conservation, i.e. functional and structural homologies, do not end at the nucleotide or amino acid sequence levels, but have been demonstrated at numerous other levels of the biological organization of zebrafish, including, for example, its neurotransmitter systems (Mueller et al, 2004;Panula et al, 2006; also see Gerlai et al, 2009) and its neuroendocrine responses to stress (Alsop & Vijayan, 2008). Conservation of function (at the gene expression level) has been found in zebrafish even in such responses as neuro-adaptation to drugs of abuse (Kily et al, 2008).…”