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