How a fly flies Michael Dickinson

I grew up watching Star Trek I love Star

Trek Star Trek wanted me it made me want

to see alien creatures creatures from a

far distant world but basically I

figured out that I could find those

alien creatures right on earth and what

I do is I study insects I’m obsessed

with insects particularly insect flight

I think the I think the evolution of

insect flight is perhaps one of the most

important events in the history of life

without insects there be no flowering

plants without flowering plants there

would be no clever of fruit eating

primates giving TED talks now David and

he Co and kotaki gave a very compelling

story about the similarities between

fruit flies and humans and there are

many similarities and so you might think

that if humans are similar to fruit

flies the favorite behavior of a fruit

fly might might be this for example but

but in my talk I don’t want to emphasize

on the similarities between humans and

fruit flies but rather the differences

and focus on the behaviors that I think

fruit flies excel at doing and so I want

to show you a high-speed video sequence

of a fly shot at 7,000 frames per second

and infrared lighting and to the right

off screen is an electronic looming

predator that is going to go at the fly

the fly is going to sense this predator

it is going to extend its legs out it’s

going to sashay away

to live to fly another day now I have

carefully cropped this sequence to be

exactly the duration of human eye blinks

and the time that it would take you to

blink your eye the fly has has seen this

this looming predator estimated its

position it initiated a a motor pattern

to fly it away beating its wings at 220

times a second as it does so I think

this is a fascinating behavior that

shows how fast the fly’s brain can

process information

now now flight what does it take to fly

well in order to fly just as in a human

aircraft you need wings that can

generate sufficient aerodynamic for

you need an engine sufficient to

generate the power required for flight

and you need a controller and in the

first human aircraft the controller was

basically that the brain of Orville and

Wilbur I’m sitting in the cockpit now

how does this compare to a fly well I

spent a lot of my early career trying to

figure out how insect wings generate

enough force to keep the flies in the

air and you might have heard how

engineers proved that that that bumble

bees couldn’t fly well the problem was

in thinking that the insect wings

function the way that aircraft wings

work but they don’t and and we tackled

this problem by building giant

dynamically scaled model robot insects

that would flap in in giant pools of

mineral oil where we could study the

aerodynamic forces and it turns out that

the insects flapped their wings in a

very clever way at a very high angle of

attack that creates a structure at the

leading edge of the wing a little

tornado like structure called a

leading-edge vortex and it’s that that

vortex that actually enables the wings

to make enough force for the animal to

stay in the air but the thing that’s

actually most so what’s fascinating is

not so much that the wing has some

interesting morphology what’s clever is

the way the wing that the fly rather

flaps it which of course ultimately is

controlled by the the nervous system and

this is what enables flies to perform

these remarkable aerial maneuvers now

what about the engine the engine of the

flies absolutely fascinating they have

two types of flight muscle so-called

power muscle which is stretch activated

which means that it activates itself and

does not need to be controlled on a

contraction by contraction basis by the

nervous system it specialized to

generate the the enormous power required

for flight and it fills the middle

portion of the fly so when a fly hits

your windshield it’s basically the power

muscle that you’re looking at but

attached to the base of the wing is a

set of little tiny control muscles that

are that are not very powerful at all

but they’re very fast and they’re able

to reconfigure the hinge of the wing on

a stroke by stroke basis and this is

what enables the fly to change its wing

and generate the the changes and

aerodynamic forces which change its its

flight trajectory and of course the role

of the nervous system is to control all

this so let’s look at the controller

now flies excel in the sorts of sensors

that they carry to this problem they

have antennae that sense odors and

detect wind detection they have a

sophisticated eye which is the fastest

visual system on the planet they have

another set of eyes on the top of their

head we have no idea what they do they

have a sensors on their on their their

wing the wing is covered with with

sensors including sensors that sense the

deformation of the wing they can even

taste with their wings one of the most

sophisticated sensors a fly has is a

structure called the hall tears the hall

tears are actually gyroscopes these

devices beat back and forth about 200

Hertz during flight and the animal can

use them to sense its body rotation and

initiate very very fast corrective

maneuvers but all the sensory

information has to be processed by a

brain and yes indeed flies have a brain

a brain of about a hundred thousand

neurons now several people at this

conference have already suggested that

fruit flies could serve neuroscience

because they’re a simple model of brain

function and the basic punchline of my

talk is I’d like to turn that over on

its head I don’t think they’re a simple

model of anything and I think that flies

are a great model they’re a great model

for flies and let’s let’s explore let’s

explore this notion of simplicity so I

think unfortunately a lot of

neuroscientists we’re all somewhat

narcissistic when we think of brain we

of course imagine our own brain but

remember that this kind of brain which

is much much smaller instead of a

hundred billion neurons it has a hundred

thousand neurons but this is the most

common form of brain on the planet and

has been for 400 million years and is it

fair to say that it’s simple well it’s

simple in the sense that it has fewer

neurons but is that a fair metric and I

would propose it’s not a fair metric so

let’s sort of think about this I think

we have to compare we have to compare

the size of the brain with what the

brain can true can do so I propose we

have a trump number and the Trump number

is the ratio of of this man’s behavioral

repertoire to the number of neurons in

his brain will calculate the Trump

number for the fruit fly now how many

people here think the Trump number is

higher for the for the fruit fly it’s

it’s a very smart smart audience yes the

inequality goes in this direction or I

would posit it now I realized that it is

a little bit absurd to compare the

behavioral repertoire of a human to a

fly but let’s take take another animal

just as an example here’s that here’s a

mouse a mouse has about a thousand times

as many neurons as a fly I used to study

mice when I study mice I used to talk

really slowly and then something

happened when I started to work on flies

and I think if you compare if you

compare it the natural history of flies

and mice it’s really comparable they

have to forage for food they have to

engage in courtship they they they they

have sex they hide from predators they

do a lot of the similar things but but I

would argue that flies do more so for

example I’m going to show you a sequence

so they have to say some of my funding

comes from the military so I’m showing

this classified sequence and you cannot

discuss it outside of this room ok so I

want you to look at the payload at the

tail of the fruit fly watch it very

closely and you’ll see why my

six-year-old son now wants to be a

neuroscientist wait for it

so at least you’ll admit that if fruit

flies are not as clever as mice they’re

at least as clever as pigeons now I want

to get across that it’s not just a

matter of numbers but but also the

challenge for a fly to compute

everything that brain has to compute

with such tiny neurons so this is a

beautiful image of a visual interneuron

from a mouse that came from from Jeff

Lichtman a lab and you could see that

the wonderful images of brains that he

showed in his in his talk but up in the

corner in the right corner you’ll see at

the same scale of visual interneuron

from a fly and I’ll expand this up and

it’s a beautifully complex neuron it’s

just very very tiny and there’s lots of

biophysical challenges with trying to

compute information with tiny tiny

neurons how small can neurons get well

look at this interesting insect it looks

sort of like a fly it has wings that has

eyes it has antennae its legs

complicated life history it’s a parasite

it has to fly around and find

caterpillars to parasitize but not only

is its brain the size of a salt brain

which is comparable for a fruit fly it

is the size of a salt brain

so a salt brain so here’s some other

organisms at the similar scale this

animal is the size of a Paramecium and

an amoeba and it has a brain of 7,000

neurons that’s so small you know these

things called cell bodies you’ve been

hearing about where the nucleus of the

neuron is this animal gets rid of them

because they take up too much space so

this is a session on frontiers in

neuroscience I would posit that a front

one frontier in neuroscience is to

figure out how the brain of that thing

works but let’s think about this how can

you make a small number of neurons do a

lot and I think if from an engineering

perspective you think of multiplexing

you can take a hardware and have that

hardware do different things at

different times or have different parts

of the hardware doing different things

and these are the two concepts I’d like

to explore and they’re not concepts that

I’ve come up with

but concepts that have been proposed by

others in the past and and one idea

comes from lessons from chewing crabs

and I don’t mean chewing the crabs and I

I grew up in Baltimore and I chew crabs

very very well but I’m talking about the

crabs I

like doing the chewing crab chewing is

actually really fascinating crabs have

this complicated structure under their

carapace called the gastric mill that

grinds their food in a variety of

different ways and here’s an endoscopic

movie of this of this this this this

structure the amazing thing about this

is that it’s controlled by a really tiny

set of neurons about two dozen neurons

that can produce a vast variety of

different motor patterns and the reason

it can do this is that the this little

tiny ganglion in the crab is actually

inundated by many many neuromodulators

you heard about neuromodulators earlier

they’re more neuromodulators that that

alter that that innervate this structure

then actually neurons in the structure

and they’re able to generate a

complicated set set of patterns and this

is the work by yves martyr and her many

colleagues who’ve been studying this

fascinating system that show how a small

cluster of neurons can do many many many

things because of neuromodulation that

can take place on a moment-by-moment

basis so this is basically multiplexing

and time imagine a network of neurons

with one neuromodulator you select one

set of cells to perform one sort of

behavior another neuromodulator another

set of cells a different pattern and you

can imagine you could extrapolate to a

very very complicated system is there

any evidence that flies do this well for

many years in my laboratory and other

laboratories around the world we’ve been

studying fly behaviors and little flight

simulators you can tether a fly to a

little stick you can measure the

aerodynamic forces it’s creating you can

let the ply it fly play a little video

game by letting it fly around and in a

visual display so let me show you a

little tiny sequence of this here’s a

fly and enlarged infrared view of the

fly in the flight simulator and this is

the game the Flies love to play you

allow them to steer towards a little

stripe and they’ll just steer towards

that stripe forever it’s part of their

visual guidance system but very very

recently it’s been possible to modify

these sorts of behavioral arenas for

physiology so this is the preparation

that one of my former postdocs gabby

Mayman who’s now at Rockefeller

developed and it’s basically a flight

simulator but under conditions where you

actually can stick and elect

in the brain of the fly and record from

a genetically I identified neuron in the

fly’s brain and this is what one of

these experiments looks like it was a

sequence taken from another postdoc in

the lab Bettina schnell the green trace

at the bottom is the membrane potential

of a neuron in the fly’s brain and

you’ll see the flies start to fly and

the fly is actually controlling the

rotation of that visual pattern itself

by its own wing motion and you can see

this visual interneuron respond to the

pattern of wing motion as the fly flies

so for the first time we’ve actually

been able to record from neurons in the

fly’s brain while the fly is performing

sophisticated behaviors such as such as

flight and one of the lessons we’ve been

learning is that the physiology of cells

that we’ve been studying for many years

in quiescent flies is not the same as

the physiology of those cells when the

Flies actually engaged in active

behaviors like flying and walking and so

forth and why is the the physiology

different well it turns out it’s these

neuromodulators just like the

neuromodulators in that little tiny

ganglion in the crab so here’s a picture

of the october immune system octo

commune as a neuromodulator that seems

to play an important role in flight and

other behaviors but this is just one of

many neuromodulators that’s in the fly’s

brain so I really think that as we we

learn more it’s going to turn out that

the whole fly brain is just like a large

version of the stomatogastric ganglion

and that’s one of the reasons why it can

do so much with so few neurons

now another idea another way of

multiplexing is multiplexing in space

having different parts of a neuron do

different things at the same time so

here’s two sort of canonical neurons

from a vertebrate and invertebrate a

human pyramidal neuron from rimoni cahal

and and another a cell to the right a

non spiking inner neuron and this is the

work of Alan Watson and Malcolm burrows

many years ago and malcolm burrows came

up with a pretty interesting idea based

on the fact that this neuron from a

locust does not fire action potentials

it’s a non spiking cell so a typical

cell like the neurons in our brain has a

region called the dendrites that

receives input and that input somes

together and will produce action

potentials that run

down the axon and then activate all the

output regions of the neuron but non

spiking neurons are actually quite

complicated because they can have input

synapses and output synapses all inter

digitated and there’s no single action

potential that drives all the the

outputs at the same time so there’s a

possibility that you have computational

compartments that allow the different

different neurons to do different of

different parts of the neuron to do

different things at the same time so

these basic concepts of of multitasking

and time a multitask in space I think

these are things that are true in our

brains as well but I think the insects

are the true masters of this so I hope

you think of insects a little bit

differently next time and as I say up

here please think before you swat

you