Whole-brain activity mapping onto a zebrafish brain atlas

Abstract

In order to localize the neural circuits involved in generating behaviors, it is necessary to assign activity onto anatomical maps of the nervous system. Using brain registration across hundreds of larval zebrafish, we have built an expandable open source atlas containing molecular labels and anatomical region definitions, the Z-Brain. Using this platform and immunohistochemical detection of phosphorylated-Extracellular signal-regulated kinase (ERK/MAPK) as a readout of neural activity, we have developed a system to create and contextualize whole brain maps of stimulus- and behavior-dependent neural activity. This MAP-Mapping (Mitogen Activated Protein kinase – Mapping) assay is technically simple, fast, inexpensive, and data analysis is completely automated. Since MAP-Mapping is performed on fish that are freely swimming, it is applicable to nearly any stimulus or behavior. We demonstrate the utility of our high-throughput approach using hunting/feeding, pharmacological, visual and noxious stimuli. The resultant maps outline hundreds of areas associated with behaviors.

The zebrafish as a promising tool for modeling human brain disorders: A review based upon an IBNS Symposium

“…optogenetics) (Chen et al, 2016;Portugues et al, 2013). "Snapshots" of whole brain activity can also be taken using in situ hybridization of the immediate early gene c-fos, a marker of neuronal activity (Ellis et al, 2012), or with antibody staining for another activity marker, phosphorylated ERK (Randlett et al, 2015). Together, this collection of tools for the interrogation of neural development and function will enable in vivo dissection of the changes that occur when ASD risk genes are mutated.…”

Correlating 3D light to 3D electron microscopy for systems biology

“…Likely. In LM, remarkably, registration of volumetrically morphed confocal z-stacks has allowed mapping of anatomy of populations of age-matched individual zebrafish larvae with near cellular resolution [66]. Registration with EM volume maps [35] may raise the possibility of comparisons of macroscopic distributions of ultrastructural features between individual animals.…”

Imaging, manipulation and optogenetics in zebrafish

“…For clarity 7 planes over the 20 are represented. As discussed before, the subpallium is believed to be responsive to noxious heat [139], which explains why it is responsive for both trapping modalities. The thalamus is interestingly responding when trapping the otolith's edge and not responsive when trapping its centre, which could suggest that it is involved in the processing of acceleration information.…”

“…Even though the behavioural responses observed and shown cannot be from heat, it does not prove the absence of heat sensation and heat information processing in the brain. Noxious heat has been studied in zebrafish [18,139,140], and multiple brain regions show activity in response to noxious heat. With those results, we know that we need to differentiate brain activity in responses to heat and acceleration.…”