Good morning everyone and
I'd like to thank Chris and Bill out for

the invitation to come and
talk to you today it's always so

nice to be able to come to a place
where you hear so many things about and

I mean this is a shameless plug for
any potential collaboration and

that could come from this talk this
is a plea for help as well with some

of the data that I'm going to show you and
so if lightbulbs go off when we're talking

about some of the big data things that
we're doing please do reach out and

I hope to reach out to you during
the course of the next few months.

The you know talks go pretty quickly and
so what I want to start off by doing

is talk to you about the people
who actually do the work and

give them all the credit all the criticism
you throw my way all the credit to them.

A lot of the work that I'm going to be
talking about today is the is the work of

two research specialists in the lab.

And so my son Igor he and then Sarah
Hunter is an undergraduate in the lab was

really taking us in different directions
with the work that I'm going to be talking

to you about but I'm not going to be able
to share too much of her walk this morning

in his work on trial run the Lebanese
American poet collegiate Brown writes and

a woman who held a babe against her
bosom said Speak to us of children and

he said us you your children are not
your children they are the sons and

daughters of life's longing for
itself you may give them your love but

not your thoughts for they have their own
thoughts you may strive to be like them

but seek not to make them like you
you may give them your love but

not your thoughts for they have
their own thoughts historical events

data collected in the aftermath of those
events and modern neuroscience prove

this to be completely false Take for
example Rachel who does work.

Rachel shown that babies who were in
utero at the time that their moms

directly experience the nine eleven
terrorist attacks had lower cortisol

levels at age one compared to a comparable
cohort of babies whose mothers

did not directly experience those attacks
Rachel's group has also shown that

lower cortisol levels up predictive of
post-traumatic stress disorder developing

in descendants of Holocaust survivors
even if those descendants did not

experience the Holocaust themselves
closer to home this work my town or

your van of which which has shown that
children born to mothers who were abused

and even if this abuse happened before
those children were conceived those

children brought into the boy to present
with hiring Zeitlin depression like

metrics compared to children who were
not abuse and then of course we know

across history starting with the Dutch
hunger winter in one thousand nine hundred

four when food and and ration was
embargoed going into the Netherlands and

then a few famines that have occurred
in Sweden in all the data collected in

the aftermath of those famines that
nutritional impoverishment has profound

imprints on descendant biology in how
they process their food mental health and

a suite of Father metabolic disorders so

if you think that this happens
only in humans that's not true and

one of my favorite examples is this
is the study with field crickets and

wolf spiders so you have gravity field
crickets field crickets who are pregnant

and those few crickets were raised into
environments high predation by wolves

spiders Olopade Asian by wolves spiders
and what they found with these authors

found is that the crickets who were born
in an environment that had high predation

by Will spiders showed defensive
behaviors to the wolf spider ODA and

did not approach that will spider ODA and
so

descendants bear profound imprints
of ancestral environments and

ancestors transfer copious amounts
of information to descendants

This happens across life stages and
this happens across species

the question then becomes how do
descendants inherit information from

ancestors and how is descending
neurobiology impacted by and

session for
environments to answer these questions.

There have been a lot of animal models
that that are allowing us to to be able to

decipher how to send in spare
imprints of ancestral environments so

take for example in the nutritional
space I'm showing you to two papers

here one by Margaret Morris says group and
the other by all you ran Doe's group and

both of these have a similar
flavor they took male wraps female

rats they manipulate their diets and
then they look to the offspring and

they show that the offspring imprints off
these altered diets such as the offspring

process their food differently
there's higher metrics of diabetes and

a bunch of other metabolic symptoms and

so when a cut came to nutrition we
already knew that you could model this in

the laboratory when you were starting out
these experiments that I'm going to be

talking to you about that was less known
from a neuro psychiatric for spect shown

here are two studies the first by David
Cruz who I coincidentally did my Ph D.

with David took
Michael Skinner's model and

what what Skinner's model is is they take
female rats when they're pregnant and

they feed them a fungus
site called been closed.

And what Michael and his group and
David in the space showed is that the F.

three generation remember it was only
the every zero generation that was spared

have been closer in the F.

three generation showed transgenerational
imprints of this particular ancestral

fungus site exposure and in this case they
looked at me preference Michael Skinner's

group has gone on to show that this
occurs across several generations and

I think they're at F eight right now
another example that I like to share is

the work by David Dietz American ness
was where you take a male mouse and

let him get beat up upon by another male
mouse that's called social defeat and

when that male mouse who's been defeated
goes on to sire offspring they found that

the offspring show higher depression and
anxiety like metrics in the lab and

so these examples show that
you can inherit information or

at least transfer information about
acquire traits across generations and

there's been a lot of work and I'll talk
about this towards the end of my talk

from Isabel months Tsui Tracy Balan
a suite of fathers trying to get us to

how this is actually happening
all of this is fine and

dandy but I think there's
still gaps that persist and

those gaps come in two flavors
one is can we prevent or

reverse the effects of ancestral
environments in descendants.

And how is this actually happening and
I'm going to submit that to answer both of

these questions we need to be able to
physically follow in some shape or

form assess a cue across generations
we need to physically follow

an ancestral experience that occurs in one
generation across multiple generations

that to me is akin to looking for
a small needle in a giant

haystack Wade you look for the imprints
of the Holocaust where do you look for

imprints of social defeat way do you
look for imprints of fungus side and

exposure that's where all faction come so

that all factory system as is known
to most of you in the room you and

I smell just like rodents smell within
our nose there are these neurons call

factory sensory neurons in the whole fact
regularly I'm I'm going to call those all

as EMS or factory century neurons or
sense send their X.

owns into the brain through
the critter form plate and

they coalesce into functional units
in the factory called Glue Merrill I

you can have millions of full factory
sensory neurons in your nose but

each sensory neuron will
only express one of

one thousand different older
interceptors order interceptors being

the locks that bind all
the odors in your environment so

that all factory century
neuron here a O.S.M.

is expressing a all red this always
sends expressing yellow blue green and

purple Why is that important
spread across the nose

you're going to have a bunch of or
sends that express red but

no matter where they are in the nose
they're going to send their axons and

those axons are going to
coalesce at the same place and

all factory Bob into a functional
unit called a glamorous.

The oil sands expressing Greene all of
them are going to go into a particular

place in the gloom era in the old
factory again called the Americas so

there's an exquisite structural
organization where you can visualize

information going into the brain in
a factory says why is this important

this is important because in the lab we
have mice way you can visualize specific.

Populations that express specific
order and perceptiveness So

here you have the M seventy
one leg Zed mouse and

with them seventy one leg said mice allows
you to do is it allows you to stain

blue all the sensory neurons in
the nose that express the M.

seventy one receptor and those send their
axons into the brain coalescing into

the olfactory bulb Why is this
important this is important

because we know that there's an odor
called a seed of pheno own which goes and

activates the M seventy one older and
receptor we also know that an odor in

propanolol does not activate this
receptor and so now not only do you have

a structural organization to the old
factory system but you also have some

kind of functional specificity
you can take this information and

what you can do is we are premise was
that you could take this information and

condition these animals with an odor so
order a shock odor shop or

a shop as you know if you know one plus
shop a seat a few no pressure opera open

all Plus shock the animals going to get
become fearful of that or would you then

have a behavioral protocol in which
a specific cue has taken on a salience and

a valence the olfactory system
already has this functional and

structural specificity in this animal and

you have a genetic locus the M seventy
one lags like you said locus in.

Seal fee known responsive factory
century neurons where you can look for

imprints of this particular old factory
experience across generations so

remember I said one of the things that
I think we need to do to be able to

understand how descendants inherit
information about ancestor environments is

actually follow that information here you
can follow that information at the level

of structure visualize it in the next
generation you can follow it at the level

of function because you can
you can look at how those next

generation respond to this particular odor
and maybe just maybe the imprints of this

experience you would find in the sperm all
the eggs of these animals which allows it

to go to the next generation Everyone with
me I'll be happy to take any questions for

the course of my talk if I don't
want to lose anyone All right so

this was where we thought we could go
from an intergenerational perspective

what do we start with so
before I go to Carrie's lab

said Jones who was a graduate student
put out a paper in two thousand and

eight where they took animals and
fear condition them

to see to feed on a problem
a special case special for

propane all plus shop propane all
pressure shown here on the Y.

axis is something called
Feel potentiate it stuff or

if you do that some of you may have
startle some of you may have not you put

an animal in a really small environment
and the animal startles that's called

startle response if an animal if
you pair that that noise bursts

this with the with a cue that the animal
has been conditioned with the animal's

going to be more fearful and a bigger
response and so what shown on the Y.

axis is fear potentiate of stopping
a measure of fear you have

animals who are conditioned to a seat
of pheno own showing a high startle to

see Tofino on but not to proper and
all animals who are conditioned

propanolol a shock protocol plus shall
show a high fear to propanolol but

not to exceed a few known so there's
a specificity of response when the animal

is conditioned with a particular
odor complimenting the specificity

was a new anatomical effect such
that in animals who are untrue

these are what the gloom era list
looks like often am seventy one lags

at animal who's not trained to any odor or
just strain with propane all

when the animal is trained to
a seed of pheno a seed of shock.

There are more sensory neurons that
express this particular older perception

that now send more axons into the brain
more axons into the brain means

a larger group Mairowitz And so
there's an enhanced representation for

that particular order interceptor in the
trained nose and in the train all factor.

So now the question becomes what if
we conditioned animals we waited for

some time allowed for them to mate
got their offspring How do their

offspring respond to this particular order
how does the olfactory system look like

in this particular in these offspring and
what are the signatures off this or

Factor experience in the sperm off these
animals who'd been conditioned all

the eggs that have been conditioned So
here's what the behavioral data looked

like shown here is something called odor
potentiate it starts to O.P.'s it's not

fair potentiate it started because we're
not training these animals these are F.

ones whose fathers had undergone
some kind of old experience or

not and then we just testing their
baseline response to these Otis

when we went when animals are trained to
a seed a fee known and then we get their

offspring so these are F one ace
offspring they show a higher Stoffel to

a seed OFI known compared to animals whose
fathers will condition appropriate all and

this is specificity of response because
when you when animals were conditioned to

propanolol they sire offspring that are
now most sensitive to probe and all but

animals who were conditioned to see the
pheno on their offspring are not showing

a higher potentiate it startled
to propane all a lot when

the when when this work came out a lot of
papers a lot of press picked it up and

said mice inherit the fear of their
fathers I'm here to stand before you

today a to get some good food which I've
sequestered away because everyone told me

I needed to know I'm here today
to tell you that it's not a fear

response you will never hear me say it's
a fear response it is a sensitivity to

that particular Oda they noses are set up

to respond to lower
concentrations of the odor.

Just tell Adam I'm
anthropomorphizing here something's

something's happening below and we know
that because we did a dose response

a conscious concentration and animals do
indeed have are able to detect little

concentrations of these particular odors
based on what the ever condition too so

this is similar to you being
able to detect the cologne of

the perfume of someone you're familiar
with ten feet away as opposed

to them having to come really close to
me for me to even detect what perfume or

cologne that they're wearing
you're just you're able to detect

lower concentrations of that odor so
it's a sensitivity not a fear and

we can talk about how we did how we figure
out whether it's a fear fear response or

whether it's appended to towards the end
of the talk so we have this enhanced

sensitivity in the next generation
what does the new anatomy look like so

when you look at F one home animals so
these are animals who are by individual F.

zeros males who are just
hanging out in their home cage

that's what the glamour look like when you
have F zero zero condition appropriate

all their offspring are male I
look this way no real change but

now in Adam olds who had no prior
exposure to see to feel but

their parents had been conditioned to see.

This is what they like there's
an enhanced representation for

the fall for
this particular odorant at baseline and so

not only was there an increased behavioral
sensitivity to the odo there was

an enhanced or factory representation for
this odor at this point we

asked the question houses happening and it
seemed like there were two possibilities.

You could either have social transmission
of information which is very akin

to cultural transmission grandmothers
A mother's telling their offspring about

what the Holocaust was about all they
could be something within the sperm or

egg that allowed for
an in heritance of information.

We wanted to tease these
possibilities apart so we did three

sets of experiments I'm not going to have
time to go into the details off them but

basically all of these experiments
suggested that there was an inheritance of

our phenotypes not a biological
transmission not a social transmission So

for example we did in vitro fertilization
and so the idea being OK maybe we've

conditioned these males maybe they've
mated with these females and and

transferred some information about
that conditioning to offspring so

what if we just take sperm from these
males do an I.D.F. experiment in

a dish to implant those into Sarra gets
Will we still get those effects and

we did so that imply to us that there
was an inheritance of information not so

much or biological transmission so
the question is how is this happening

B L U E is blue for

an all of seventy one lakh said sensory
neuron in the EV's ear Generation and

B L U E is blue for an M.

seventy one lacks said neuron in the F
one generation what we thought was

happening is you're making a lot
of blue with a lot of blue.

And so we turn to epi genetics.

The ability to read how
the genetic code how much

of a gene is expressed versus not and
this is an embarrassingly simple

cartoon of happy genetics but
it shows you two flavors one is D.N.A.

methylation which I know a lot of people
in the room study so you have metal groups

there it's there that are attached
to C.P.G. sites in the genome we

now know that metal groups are not
only the purview of C.P.G. sites and

that's a conversation for a different
time and then you have histones around.

The D.N.A. D.N.A. woven around histones
which which tell a particular locus

All right come in transcribed me or
if there's another set of histone that's

going to say no I'm not available to be
transcribed and so what you're doing is

you're allowing for a particular genetic
locus to either be transcribed on not

so if this if this information went
through the sperm which I.D.F.

experiments suggested then we would have
to have some kind of clues as to what's

going on in the sperm and so
we looked at histones at the M.

seventy one locus in the sperm of animals
that have been conditioned with the seed

of pheno no prob and all and
so absolutely nothing so

that point we sent the soft active
motif to do by cell fight sequence and

we now do this in the lab at that time we
didn't have the ability and so we sent

a tract of multi Now what I'm showing you
here is percent methylation on the Y.

axis and
you can see that in the F A zero sperm so

these are animals who've been conditioned
to see to feel known there is a modest but

significant decrease in methylation
compared to sperm from animals

who have been conditioned
appropriate all this was known on

every olfactory odor interceptor that we
looked at because when we look at all of

our six which is not activated by a seed
of pheno and we don't see this difference

in methylation I am not
here to say that D.N.A.

methylation is what is giving us this
causal mechanism that allows for

the inheritance of our phenotypes
across generations and

I'll tell you what I think it is
towards the latter half of my talk but

what I'm here to say is that we think
that D.N.A. methylation gives us so

readout that something salient
happened to the animal and

dispose is registering that
information if you think that's

farfetched I'm only going to draw your
attention to more data coming out from

from from fathers who are often
advanced paternal age and

we know that a lot of a lot of the birth
issues that we might be seeing is because

of D.N.A. methylation marks being a crude
all stripped away in the sperm of those

fathers and so D.N.A. methylation
in the sperm is a pretty big deal.

But we using it as a readout of saying

that there's an all factory experience the
sperm is registering it in some shape or

form whether this is causal or not I think
is a topic for another conversation and

I think some of the technology
needs to catch up so

when we send this paper out we show
that these effects went into the F.

and F.

two generation as well which the review
was taught to talk to tell us so

now show us that this methylation
is also present in the F.

one sperm and so we went ahead and

did that experiment and we see
a decrease in methylation even in the F.

one spoke of animals who saves erode
had been conditioned to a seed

of female so what I've shown you the US
far is before I came into the lab

you could take an odor and shock an animal
and that animal then showed a feeler to us

that odor and then had an enhanced
representation for that Odo in its brain

we were able to show that this resulted
in a decrease methylation in the sperm

of these animals at that particular
order intercept the locus

when you train the next generation
when you expose the next generation to

the older they had a higher startle
to that particular odor and

an enhanced representation for that odor
in the brain and this was at baseline and

we also showed that these effects
persisted into the sperm of the F.

ones giving us an effect in the X.

to generation I should I have this M.R.
twenty three G.F.P. would like

to remind myself to tell you we also have
another mouse in the lab which is them

are twenty two G.F.P. mouse where twenty
three neurons can be stained with G.F.P.

or express G.F.P.
Lyra is an odor that targets those and

we see all of these effects even with
that particular order or pairing and so

this is not something specific to a seed
a few known it you can see this with

different orders so
at this point you should be saying what So

I want to I want to draw your
attention to two experiments

one is this beautiful work by
Giotto drank Indigo Restrepo while

working with Diego Restrepo where
what they did was they fed maam.

A particular diet either either
a seed of pheno own or mint and

we know that these particular
odors will activate one older and

receptive versus another and they did
that at different points of gestation and

what they showed is that there was
an enhanced representation an increase

which in the offspring for
that particular older interest scepter

when Mom was fed that diet at
different points during gestation

almost identical to the work that we
propose we published ZIV WILLIAMS

put out a paper using fruit flies where
you can condition fruit flies and you see

the say olfactory condition fruit flies
and you see the same effects in the F.

one generation of the F.

two generation as we saw but Xavier with
the power of genetics was able to go and

turn on and off mushroom body neurons and
show where that particular.

Processing was happening and how he could
reverse those effects or prevent those

sensitivities from going to one generation
and then to the next generation so

we don't think this is something specific
to mammals in fact we know a lot from

the honeybee literature this kind of stuff
happens all the time depending on foraging

availability in terms of what
the order odor and bouquet is vailable

to honeybees and now we know that it's not
specific to mammals because we've seen

this in fries as well we can
talk about whether we think

this is generalizable to other sensory
modalities towards the end of the talk

so the question now becomes All right so
this is been shown not only by us by other

people as well in this work by Regina
Sullivan who's done things we told us and

intergenerational as well the question is
What do you do with this information and

that hit home to me when we're talking
to retired general people here early

Who's question was What would you like
me to do not enlist anyone in the U.S.

Army whose parents or grandparents
suffer from P.T.S.D. earings ID.

Because of their own deployments or

because of their own mental
health issues and so

this is where these kinds of conversations
take on a different meaning and so

on are and what we need to ask ourselves
is can we reverse these effects and these

are the gaps that I was felt about for the
first gap was prevention or reversal and

the second was mechanism can we reverse
these effects because if you can reverse

these effects maybe we can buffer future
generations from the detrimental effects

of ancestral traumas or
we can break cycles of inheritance so

can we return to extinction
training in animals to try and

tease us apart what extinction training is
is you have several groups you have a home

cage group you have condition with the sea
to feed on which is what I've been talking

about a special case but shock you have
exposure to a sea to feed on which is just

a Safe Space Ace but then you have THIS IS
THE MONEY group condition with the C.D.O.

fee known exposed to a seed a female and
with no shock and so

what that means is a special case but

shock a special so the animal
becomes fearful of that odor and

then you extinguish that fear response
by doing ACE ACE ACE ACE ACE And so

the animals fear response will
diminish over time or that's what we

thought would happen to film and Morrison
when she was a graduate student with Cary

put out this paper where she took what we
would consider every serial animals and

she trained them to fear a seed a few
known and then chicks sting and then

she subjected them to extinction training
so what feel men are showing you on this

graph is the percent freezing so you can
see when animals are trained to see Tofino

and you have a high fear response and
then when you train them to see to feed on

with subject them to extinction training
that fear response decreases over time

what film was also able to show is that
this an enhanced representation for

the M seventy one lakh said neurons
six weeks post conditioning but after

you extinguish those animals after you
after you perform extinction training that

that enhanced representation comes back
down to baseline so they does seem to be

a malleability within the ever generation

the question then becomes can
we reverse effects in the F.

one generation after extinction
training that after zeros Everyone with

me OK So here's what the data
looks like the answer is yes and

we're trying to publish
these these data right now.

When you take animals who've been
conditioned to see a few known

their offspring show a higher
sensitivity to see Tofino And

just like we showed earlier but when
you train animals to see to feed on and

then extinguish their responses you see
that that sensitivity decreases and

that is complemented by the enhanced
representation for the good Maryla seen in

the F one a Santa ML's which then goes
back down to baseline when you've

trained they have zero zero and extinction
and then extinction train them so

there is again a malleability to this we
just don't know how this is happening but

remember I told you we look to the sperm
to see if they register information about

all of this and about all of this or
Factor experience and so we can partially

rescue in the sperm the methylation
Mox we see a decrease in methylation

at them seventy one lag said locus
in the in the ever sperm and

when we extinguish those animals with
the seed a few known we see a reverse so

too big to words baseline I'm not going
to say that a reverse is completely and

we can show this with as well so

why does this matter this
matters because way back when G.

by easy was talked about a lot
it still talked about a lot gene

by environment interactions
epigenetic serves as that bridge

that allows us to understand how
environments might influence

gene expression to give us
a particular phenotype and

we know that this allows for a lot of
developmental regions of health and

disease that allow for one individual
to go down a risk scenario the other

individual to go down a resilience and
based on their environmental experiences.

But I think what these data also show
is that not only can loan sensitivities

be propagated across generations but
also their reversal so

there is a malleability which we need to
be able to tap into because otherwise for

the most part would be pretty screwed
if every environmental experience had

replications in the next generation and
for the most part we're not and so there

is this malleability the question is what
is the launch of that malleability and

how is that happening so what I've
shown you this far is that in an F.

zero generation you
could take an order and

a foot shock you could make that
animal feel full of that odor and

have an enhanced representation for
that odor in the brain and

feel man was able to show that you could
reverse that with extinction training

where we were able to show with this
intergenerational experiment is that via

sperm mediated inheritance of information
I.V.'s derived F one and F two

offspring have an enhanced representation
for Odo and a behavioral sensitivity for

that Odo which we can reverse on
published data with extinction training

so there you have a scenario now where
we followed that information and

that genetic haystack but
a lot smaller all factory genes and

that needle got a lot bigger which was
that older interest scepter older and

receptive but not so
quick how is this happening and

to address how is this happening you go
to get at one of the critiques of this

particular field so I found the best way
to address the critics is to just write

about them yourself and
the critiques of the field to forget my or

factory story take any
intergenerational inheritance phenotype

out there how is any of that information
about the environment getting to the sperm

or the egg in one thousand thirty eight
August wisemen propose of the sperm and

egg are immune to everything around
them all insults around them so

how is any information getting
to the sperm and the egg and

I'll address that in
a minute the critique B.

is this this is a concept of genetic
reprogramming So you have epi genetic

marks being laid down his stones D.N.A.
methylation whatever you want but

they get scrubbed away they get a raise
at different points during development.

So how is any marks which are laid down
by environmental experiences how are any

marks escaping that epigenetic
reprogramming that's a bigger question

than me but thankfully we have a ton of
people who've been working on this stuff

and most recently put out a paper
a companion piece with in a pretty big

Journal where they looked at primordial
germ cells human primordial germ cells and

found that there were twenty five percent
of the low side that escape reprogramming

these twenty five percent of the low
side were associated with obesity and

schizophrenia now what the law behind that
escaped from reprogramming is why and

what what ramifications that has I
think is the wave of the future but

at least we know that there are all
factors that there are genetic lowside

that do escape genetic reprogramming So
the question is how is this happening

when we try to put out this paper we and
I think it's been a while but

in the discussion we said
our name might be mediators

of into generation heard since I can
show you the e-mail where the editor or

the reviewer said that
is the suffer of science

fiction twenty seventeen
that's exactly what we know

all right all of these papers
in some shape or form have done

this experiment they've conditioned their
animals are they stressed their animals or

they manipulated the diet of their
animals they've gone extracted sperm

they've got an R.N.A. from that
sperm they've injected that R.N.A.

into single cells zygotes and
they recapitulated all of their effects

Tracy males group took
nine micro R.N.A.'s and

injected it into a single cell zygotes and
got all of their facts so

at this point R.N.A. are the frontrunners
in terms of carrying into

generally into generation information
about ancestral environments and

so what we have working to our
advantage right now is we have a point.

Of trauma of stress we have the nose so
all we're doing right

now is we're profiling R.N.A. in the main
all factory up with helium in animals that

will stress versus not with the we the
odor we're looking at circulating eggs or

zones which have these tiny best
coursing through circulation and

they were looking at sperm to see
is there any correspondence and

just to give you I mean I just find it
amazing that people have thought about

this stuff before way back when Charles
Darwin proposed this concept called gem

mules little gems floating through
circulation that would allow for

information to go from one part of the
body to another including the germ cells

we would call those eggs are zones right
now eggs are Soames blabbing off from

every tissue that we can conceivably think
of where what those are carrying where

they're going I think that's the stuff
that I know a lot of people in the room

are working on if you are engineering
exits omes that I can then track

please please please drop me an email
we would love to be able to do that

I've had some conversations
with people but

I want to further those conversations so
in the last minute or

two I want to tell you where is this going
so when I send this stuff to and I H.

This they tell me that
all faction is to me.

It doesn't have translational relevance so
hopefully N.S.F. will bite.

We can hope and pray for a miracle.

But truth be told I've worked on
a lot of different species but

I've always I wanted to come back to the
psychiatric space and so leveraging really

generous collaboration's of the Okies
Primate Center we're doing some stuff

in non-human primates so I'm just
going to show you what we're doing and

the data just coming off the sequence and
we're doing the bio informatics on it so

we're doing in collaboration with people
like Mark Sanchez and Elise morron

Mark Wilson vast McCall Plus Jessica raper
and just in back of L.A. is we have.

Depending on males or females we're
getting plants eggs those omes

all sperm from animals who have
been maltreated as infants

from individuals who offer
higher a low social rank from

individuals who've been raised by their
mothers versus raised in the nursery and

we also have individuals who are
administering cocaine self administered

cocaine and so the question is
are there biological signatures that

are conserved across these different
stressors within the blood and

in the sperm that will then
predict what future offspring or

even within a generation will predict
what the behavioral phenotype will be so

here I'm showing you our
ability to to isolate eggs or

Soames from the mouse as well as
the monkey and then we have R.N.A.

coming off really small R.N.A. coming off
these particular eggs as omes you don't

expect are in a long long are any
species to be found in these eggs or

Soames and then here I'm showing you our
ability to get really high quality R.N.A.

from from a cat sperm and
we do this in a mouse form all the time so

why bother what's the big What's
the bigger What's what's the bigger goal

once we identify these signatures we can
either engineered those signatures in

the lab and then inject them into embryos
but what we are right now doing and this

is the work that it is really powering in
the lab with the help of Dr Anthony Chan

who's helping him tremendously
we're injecting stressed R.N.A.

which we obtained from sperm of those
animals who've been maltreated or

not on cocaine or not and then the idea is
to inject that stress R.N.A. into the male

pro nucleus let the embryos develop to
the sixteen cell stage and that embryo now

has a legacy of infant
maltreatment of maltreatment and

cocaine in some cases and
the idea is how we're going to push or

pull the embryo down or
risk versus a resilient trajectory.

And so that's I think everything that I
wanted to talk to you about today these

are the many faces of us hasa Analisa
not in the lab but really helping us

with the bar informatics and a lot of the
monkey work I haven't had time to talk to

you about Archon us work where we're
working on fear within a generation and

the neural circuits underlying fear
inhibition Kristi's been working on Astra

sites and all the undergraduates who
help out with their own projects thanks

to my funding sources I find that this too
much shade thrown on too many people's

work these days I don't believe this and I
don't believe that I'm not in the religion

business so this is my antidote to that
these are people whose work inspires and

informs me I'm thank you for
your attention.

Yeah thank you.

F one right yeah so
you bring up a great point the ship

sometimes already sailed with their
zeros and so how do you go in and

reverse that in a generation that
you have access to and so absolutely

that's the that's the kind of stuff
that we need to do yeah I agree there.

In the F.C.C.

rose as well in their videos as well.

Right.

He doesn't write so that was our ace
exposure group and we don't get that

effect so I think there's something
about the stress so that's allowing for

this effect to go through and we don't
know what that stress phenotype is one.

In

the F two You mean yeah

so that that's a really good question I
don't know the answer to that you know

people talk about genetic assimilation in
some way so you have maybe an epi genetic

mechanism and then it gets fixed in the
genome I think that's way too early for

something to get fixed so the hypothesis
I have is that if we actually took F.

three F.

four it would actually get diluted away
unless you give it a booster so to

speak because it doesn't make sense for an
animal to remember this particular salient

environment if a seed of a known is no
longer around and so that's something that

we're going to test in the lab to see do
you need an environment to constantly be

salient to get in to get this propagation
across many generations and get.

All.

Tons of different yeah yeah yeah and
so you know it's a question of

which ones do we look at is it going
to be only one versus another so

you bring up a point which I
think is well taken the whole

factory field typically thinks of older
interceptor choices being stochastic or

random and so then it's a question
of are we really forcing.

Choice with some of these kinds
of protocols that we're doing and

I think the Joeys still out on that and
you'll have people who say yes that can be

activity dependent olfactory
receptor choice but

then a lot of that is also stochastic so

Fidelman is trying we're trying to put out
a paper the way we it's more survivable

not so much neurogenic not so
much proliferation So we've done some.

Studies where it's more
survival not proliferation.

It goes through the female
in huge to the reason we

focus on the male mice is just because we
can get a lot more sperm compared to eggs

we have not done that experiment and
I don't know what we'd expect.

There's a lot of literature to suggest
that mom can buffalo things that happen to

Dad And so I don't know that
could go either way yeah thanks.

Yes yes.

Yes yes.

Right.

Right so
I think the first part yes a lot of.

A lot of people of have talked about the
fact that how did how did folks you're in

a cat odor become
an innate predatory scent.

And at some point somewhere it needs to be
have started that initiations are being

hardwired and so is this that kind
of possibility so Gene Robinson who

does a lot of work with honey bees wrote
a piece on the evolution of instinct and

cited this work I stay away from those
kinds of things because they're out of my

real house but that that premise
has been put out there using it

as a control I think I see your point but
I feel like folks you are in a cat

OTOH is going to be so innately averse
of these effects are more subtle and so

I think then we're comparing
different shades of responses and so

I'm not so sure what we'll be able to
tease out I'll go there and then comes.

Up.

I did not cover that so thank you for

asking me I'm I only have I'm only
a consultant on these projects I'm not

involved Regina Sullivan does a lot of
work where she can parent odo with mom and

that becomes in rats and
that becomes an appendage of the order and

there's a preference response so
when Regina pairs of students pair

a particular order with Mom they
find that preference goes to the F.

two generation and then we're trying
to do so they're trying to do some

studies with with respect to the mechanism
as to how that's happening so

we don't think it's only an aversive
experience we think it's a parrot as well.

I'll go there and
then come back to spreading the wealth.

Great so

the I can answer that

question I guess let me try to answer
it in different ways maybe but

I don't think this announcer One
is we can say which males loan to

bout that although a lot more than
a splash shop Association and

which gave us the highest fear response
and then do we see correlations with

the anatomy and the behavior in
the offspring we haven't done that we

don't select any males at all so we don't
pre-select we just take all the males and

all their offspring so
that's one way the second way I think and

I think this is where what you might
be getting to is I don't know the on so

in terms of are all the three
million sperm in ejaculate

affected equally with an environmental
experience and that's

going to have single cell approaches that
we're going to have to take the bat and

also question of which sperm
which sperm precursors.

Preempt the question about eggs I don't
know whether all eggs are going to be

affected you have eggs that are arrested
in a particular state of the lot of

the cell cycle so then does it
matter if Mom is only influenced

only gets an environmental trauma
when she's just all violated and

there's one egg which will bear that
imprint all weather all her eggs

by that imprint Those are questions that
I just don't know the answer to How come.

The.

Show so let me let me just

take a step back question is
a nuanced one in the EV's euros

I don't think that the enhanced structure
representation is related to behavior.

Because you can train an animal to
see if you don't press shock and

get a behavioral response tomorrow but the
but the good memories response comes on

three weeks later and so they're writing
there's a dissociation we went with all

faction because we knew that this
genetic architecture existed so

in thinking about could this be done
with all the tree cues I suspect not but

I can invision it being
with say with visual and

with gusto ation because there are similar
mechanisms in play with rods and

cones being in coded and representation
is being changed based on environments so

I can see visual and station but
not so much auditory information.

The out I

mean I do not think we get this effect
with single exposure we haven't tried this

this experiment but you know I
think that's a good point because

when you talk about something
that is traumatic it's not so

you talk about a multiple hit hypothesis
you're talking about early childhood abuse

and then you have something happen in
adolescence and then something happened in

adulthood and so there are these different
phases of our ability where I don't think

it's only a single exposure that's
going to give us an effect or

even within if only child abuse was
the only trauma it needs to happen for

a sustained period of time to allow for
those effects to actually manifest and

so I think the trauma all the stress
in our in our animals the stress

needs to occur repeatedly for
us to get some effects Yeah.

Yeah so
we're talking I'm talking to someone

to try and figure that out to see out
of North Carolina to see if we can get

sperm from soldiers who before they go
into the army versus go into combat

versus after they come back but that stuff
comes with its own attendant issues but

we're trying to do that yeah
all right thanks everyone.