What makes mosquitoes hungry

Research which could help to mitigate the danger of these insects to humans...
04 July 2022

Interview with 

Trevor Sorrells, Rockefeller University


Many regard mosquitoes as the world's most dangerous animals because of the diseases that the females transmit when they feed on us. They need blood to provide protein to support their egg laying. But other than the fact that they are attracted to the CO2 in our breath and the heat from our bodies, we know relatively little about how their feeding behaviour operates. And that's what Trevor Sorrells, at Rockefeller University, has been studying. He's been using the technique called optogenetics to fool mosquitoes into thinking they've just smelled a whiff of carbon dioxide. This, he's found, puts them into a "feeding mode" that seems to control a host of other downstream behaviours...

Trevor - Mosquitoes are micro-predators: they attack small quantities of their prey at a given time. And so this gave us inspiration to understand this behaviour that they use to find humans. And we wondered whether it had some similarities with larger predatory animals that hunt their prey over long periods of time. And this question of timing hadn't been examined. So we set out to understand whether mosquitoes have a sort of hunting state in their brain.

Chris - Is that in the way that if I felt hungry and I thought, "right, dinner time", I would lock myself into dinner mode and then my goal would be, "I'm going to make dinner." And I wouldn't stop until I'd eaten. Is that what you're saying? That they have a sort of default mode they go into that says, "Right, it's dinner time and I've smelt a human, now I'm on the scent of a human. I'm going to go and find them."

Trevor - Yeah, exactly. So if you were very hungry and you were walking down the street and smelled pizza, you might search around to try and find where the pizza smell is coming from. And until you locate your pizza shop and have a slice, then you'd be in this hunting mode.

Chris - Would that be indefinite? Would I carry on in hunting mode until something turned it off or would there be a time clock running?

Trevor - Yeah, exactly. And this is the question we set out to answer. It is also an important question because it has a lot of implications for how mosquitoes are able to find humans and bite us so effectively.

Chris - Obviously they're dubbed flying hypodermics and also the world's most dangerous animal, aren't they, in terms of the disease burden that's linked to them. How did you actually go about looking at this?

Trevor - We used a technique called optogenetics, which gives us the ability to activate neurons using light. And this is an advantage because it gives us really great control over the timing of when the neurons are activated. We used it to activate the carbon dioxide sensory neurons - carbon dioxide being a major component of our breath. So we put this channel that responds to red light in the neurons that respond to carbon dioxide. And so when we shine red light on them, it causes these neurons to activate and simulates the experience of carbon dioxide for the mosquito. And so we refer to this as fictive carbon dioxide.

Chris - I suppose one of the advantages of doing that is that you can be very precise in terms of when you give the stimulus and how much stimulus. It's not like blowing some CO2 at a mosquito and not knowing how much it's really smelled. This way, you actually know what the stimulus was when it was presented and in what sort of amplitude.

Trevor - Yeah, that's exactly right. And it's very hard to control gases because you don't know exactly where they are. And so we know exactly where, how much and when the mosquitoes are receiving this fictive carbon dioxide stimulus.

Chris - So that simulates a mosquito running into a human or an animal that's just breathed out. So what happens next then once it gets that stimulus?

Trevor - So mosquitoes respond to the fictive carbon dioxide stimulus by flying, which is well known as the response of mosquitoes to carbon dioxide. They also showed a lot of walking and this behaviour called probing, which involves the insertion of their proboscis into small crevices. So if a mosquito has landed on your clothing, then they show this behaviour of probing. So you would be very familiar with this, but what was surprising about our results is how long they do it for. They have this response for up to 15 minutes after just a brief fictive CO2 stimulus.

Chris - So that would be like flicking some kind of switch. It basically is the master switch that says, "right, feeding time" and activates all those other behaviours.

Trevor - That's what it appears to do. So these are a number of behaviours that the mosquitoes exhibit, but they have also altered responses to subsequent stimuli that occur later in time, or while they're in this hunting state. And these include additional cues that they use from the human host, like heat and the taste stimuli, that are present in our blood.

Chris - The one thing that we haven't discussed with this is the difference between males and females, because it is the female mosquitoes that do the blood meal feeding and the males don't do they. So if you do the experiments on males, what happens to them?

Trevor - So male mosquitoes do not feed on blood because they don't need to produce eggs. However, the males, when we tested them, they showed a strong response to fictive carbon dioxide. But the response was about 1/10th the duration of the female's response. This was interesting to us because it showed that males, while they have the ability to detect the carbon dioxide stimulus, they do not have this persistent state that we think is associated with blood feeding specifically. So males, it has been shown, do respond to carbon dioxide in order to get closer to humans and to mate with females in their vicinity. So we think that this time scale of the response of males and females is one of the reasons that the state we've discovered is specific to the goal of feeding on blood.

Chris - Does that also potentially give you a way to find out how this works? Because if you can look what is happening in the female brain, but absent from the male brain, that perhaps might be whatever that platform is that's subserving this timing mechanism.

Trevor - Yeah, that's one really interesting way to get at the neurons that control this persistent state, which is my goal for future research. Exactly as you said, to compare males and females and to understand which neurons are different in the male and female brain, because we would expect that if not the neurons that control the persistence of the state, it would identify the neurons at least that are somewhere in the circuit that control the persistent state.


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