How Animals Sense Danger

Zebrafish, a popular model animal in biological studies, can perform fear conditioning as well as human and other mammals. Professor Kawakami’s group has succeeded in developing technologies for visualizing and manipulating specific brain neurons in zebrafish by employing the yeast transcription factor Gal4, the green fluorescent protein (GFP), and the botulinum neurotoxin (BoTx). They have generated a collection of transgenic fish lines being used to study brain functions as well as other various organs by zebrafish researchers all over the world. Of the nearly 2,000 such transgenic fish lines in his lab, one played an important role in the current study that labels neurons in the dorsomedial (Dm) area of the telencephalon of zebrafish.

“In mammals including human and mouse, fear conditioning is mediated by a brain area called the amygdala. The amygdala integrates information about dangerous events, like electric shock, and some signs, such as visual or auditory stimuli. However, in fish, such neurons have not been found.” Prof. Kawakami said.

“It is important to explore such neurons in fish because we can increase the knowledge about fundamental neural circuits for animals to perform evolutionary conserved fear conditioning”

For this purpose, Dr. Lal, a former graduate student in his lab, developed a behavioral analysis system. Fish are placed with a small tank with two compartments. Green LEDs are not harmful to fish. They gave electric shocks while green LEDs are on ten times a day for five consecutive days. Finally, when green LEDs are on, fish learned to escape from the compartment which was illuminated, and moved to another compartment.

“It is fun to see how smart they are” Dr. Lal said.

Using these technologies and resources, they have found that neurons in the region called Dm of the telencephalon of fish are essential for fear conditioning. Namely, these neurons are a functional equivalent of the amygdala of mammals. This result is a clue to clarify the structure and evolution of the neural circuit essential for fear conditioning.

Prof. Kawakami showed us his zebrafish facility where thousands of fish tanks can be seen, each of which contains genetically different fish that can turn on, or drive the GFP or BoTx expression in different types of neurons in the brain or in the body.

“This work showcases a successful application of our genetic resources in the study of the brain function. It is also expected to be the basis for clarifying the causes and treatment of diseases involving fear and anxiety and PTSD.”, Prof. Kawakami said.

This study was supported partly by JSPS KAKENHI Grant Numbers JP15H02370 and JP16H01651, and NBRP from Japan Agency for Medical Research and Development (AMED).

Contacts and sources:
Koichi Kawakami
Research Organization of Information and Systems
Citation: Identification of a neuronal population in the telencephalon essential for fear conditioning in zebrafish.  Authors: Pradeep Lal, Hideyuki Tanabe, Maximiliano L. Suster, Deepak Ailani, Yuri Kotani, Akira Muto, Mari Itoh, Miki Iwasaki, Hironori Wada, Emre Yaksi and Koichi Kawakami
BMC Biology201816:45 https://doi.org/10.1186/s12915-018-0502-y © Kawakami et al. 2018
http://dx.doi.org/10.1186/s12915-018-0502-y