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LAB LIFE 3 - Aggression in Zebrafish



Following on from my post 2 weeks into my internship I’ve finally wrapped my head around the science of my project. I can now better answer the why of what i am doing.


If you haven’t read that post, click here and then come back.




My Topic: Neurochemical consequences of histamine dysfunction studied in a histamine-knockout zebrafish

Now that you’re all caught up, lets recap a little


Neurochemical = chemicals usually found in the the nervous system. The nervous system is made up of the brain and spinal cord. For my project, i am focusing on the zebrafish brain.


Histamine is a neurotransmitter in the brain. It is not one of the main neurotransmitters but there have been studies that link histamine and aggression in animals.


So my project looks at histamine knockout zebrafish, meaning the gene that is responsible for the production of histamine has been removed.



What is aggression and why study it ?

Aggression in animals can be described as an adaptive behavior which animals display in everyday life for survival, assertion of dominance and even mating. Aggression in animals can also be detrimental to their survival.


Aggression in humans can simply be defined as feelings of anger or antipathy resulting in hostile or violent behaviour; readiness to attack or confront.

Studying aggressive behavior in animals can help better understand disorders that result in aggressive behaviour in humans such as ADHD and schizophrenia. Aggression in humans occur due to a multitude of factors (genetic factors, environmental and the effect of neurotransmitters).




Why use a fish to study something that affects humans?

Firstly, we can’t use human subjects for obvious ethical reasons. Zebrafish are used as the genes and neurotransmitters that control aggression in humans can also be found in zebrafish. 69% of zebrafish genes have evolved from the same ancestral gene as humans.


Zebrafish are used due to their short generation time and they are ideal to measure under laboratory procedures. They become adults in a short period of time and they show changes in behaviour that are easy to measure. My project did not involve the behavioral aspect of modelling aggression however, i dealt with the neurochemistry ie the stuff that goes on in our brains.


So the brain stuff !!!

I was testing a model of histamine dysfunction (mutant) vs the normal ( wild-type). The mutant had the gene that produced histamine removed and the wild-type could still produce histamine.


The zebrafish brain is dissected and cut into the four brain regions. The sections of the brain are then broken up, centrifuged and the liquid extracted contains the different neurotransmitters. The levels of the neurotransmitters are then measured using a HPLC( high- performance liquid chromatography machine).



HPLC Machine

HPLC machine is a fancy way of separating out the neurotransmitters according to their retention times. Think back to primary/ gcse experiments where you did paper chromatography and separated out a dot of black ink.


For the experiment, the zebrafish have to be killed. The use and killing of animals in science is heavily regulated and is never done in a wasteful manner or if it wasn't absolutely necessary. Measures are taken to make sure the animal is killed in a humane fashion. Since working in the lab i have had a greater appreciation for the safety measures and regulation made to ensure experiments are all ethically correct.



SO what does histamine have to do with aggression ?

Not many studies have been done on histamine hence my project lol . So we are yet to find out its exact links to aggression. Histamine has been found to control other behaviours in zebrafish . Its link to aggression has been proposed to blocking the 5HT receptors. 5HT is a neurotransmitter and is more commonly known as serotonin, the happy hormone .Serotonin is thought to have an inhibitory role in aggression .


In simpler terms, the presence of serotonin decreases the level of aggressive behaviour. Therefore if histamine blocks the signalling of 5HT an increased level of aggression is expected.





It's been a very interesting four weeks and now almost 6 weeks into my internship i am appreciating all the little details that go into research. My supervisor has been very inspirational and encouraging. Its easy to forget or take for granted how much time and effort it takes to host a student in a lab. This is an opportunity i will not forget and the lessons learnt thus far will stay with me and help me immensely in my professional journey as a scientist.







References


1. Filby, A. L., Paull, G. C., Hickmore, T. F. & Tyler, C. R., 2010. Unraveling the neurophysiological basis of aggression in a fish model. BMC Genomics , 11(1), p. 1.


2. Jones, L. J. & Norton, W. H. J., 2015. Using Zebrafish to uncover the genetic and neural basis of aggression, a frequent comorbid symptom of psychiatric disorders. Behavourial Brain research , 276(1), pp. 171-180.

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