Animal Communication Animal Communication Focus on Vocal - - PowerPoint PPT Presentation

Animal Communication Animal Communication – – Focus on Vocal Learning Focus on Vocal Learning Focus on Vocal Learning Focus on Vocal Learning

Stephanie A White, PhD Dept of Integrative Biology and Physiology UCLA UCLA June 2010 June 2010 UQAM Summer Institute on the Origins of Language

Language Language

• A major component of what makes

A major component of what makes humans unique

• Sensory motor conceptual intentional
• Sensory-motor, conceptual-intentional,

recursion (Hauser, Chomsky & Fitch; Science, 2002) P d ti f b t t

• Preadaptions for subcomponents must

exist in other species.

The vocal learning sub-component

• The ability to modify motor programs to make

new vocalizations

• Used in mimicry, but can be creative
• Accomplished via hearing others and auditory

feedback of self

• Not to be confused as association of innate

sounds with objects in the environment

• Not ‘uniquely human’ yet, critical

t f ll b i to a sense of well-being

The KE Family Speech Deficit The KE Family Speech Deficit

• videos

Timmy w/speech therapist 'Friends' Timmy w/speech therapist You Tube clip

Need for non-human animal models

How can we prove that a given species is capable of vocal species is capable of vocal learning?

Brief Communication Brief Communication Nature (2005)

A i l b h i El h t bl Animal behaviour: Elephants are capable

• f vocal learning

Joyce H. Poole, Peter L. Tyack, Angela S. Stoeger-Horwath and Stephanie Watwood

“T i l i t d d “Two animals coin unexpected sounds as a surprising form of social communication ” communication.

Sonograms of vocalizations

z

Mlaika Calimero

ncy, Hz equen Fre Time, sec

Sonograms are visual depictions of sound Sonograms are visual depictions of sound X axis = frequency (pitch), y = time, darkness = amplitude

Evidence for elephant vocal learning

Scatterplot of frequency vs. duration of calls. Ml ik ' i it ti ( t i l ) bl t k d (li ht bl Mlaika's imitations (green triangles) resemble truck sounds (light blue triangles) and differ from her normal calls (yellow (yellow triangles) triangles), which resemble calls of other African elephants (dark blue: stars, adult female; diamonds adult male; squares female calf; hexagons male

African elephants not only sound different f I di l h t

female; diamonds, adult male; squares, female calf; hexagons, male calf). Calimero makes chirp-like sounds (pink circles) similar to the chirps of the Asian elephants (red circles) who lived with him.

from Indian elephants…

…they look different too! African elephants Indian elephant

Songbirds are ideal for the study of vocal learning

D A D

S

O N

S

O N

Developmental timeline/Critical periods/Auditory dependence

Relative timing of human vs. zebra finch vocal learning vocal learning

Babbling/ language-specific speech perception First words!

3 6 9 12 months uman

Universal speech perception p p p

20 60 100 days nch H Fin

Sensory acquisition Sensorimotor learning Hatchling 13days 17days Fledgling Adult Crystallization

Adult singing: practice vs Adult singing: practice vs. performance

Undirected Directed

adapted from Jarvis et al (1999)

Normal song development

Crystallization

Normal song development

Sensorimotor Learning Sensory Acquisition

A B B A

Sings A Sings B>A

50 100

B A

Sings B>A

Post-hatch day

Deafening

Crystallization Sensorimotor Learning Sensory Acquisition

Deafening

15 35 65 90

Post-hatch day

Vocal learning depends on hearing

Zebra finch Eastern phoebe

intact deaf

The Eastern phoebe in contrast to The Eastern phoebe, in contrast to the zebra finch, is not a songbird and doesn’t need to learn its song

Wilbrecht & Nottebohm, 2003 Kroodsma & Konishi, 1991

Isolation from tutor

Crystallization

Isolation from tutor

Sensorimotor Learning Sensory Acquisition

Isolation

50 100

Post-hatch day

50 100

I solates learn new notes when controls do not

I SOLATE CONTROL

Pre- tutor

65d

TUTOR TUTOR

Post- tutor

86d 86d

Two similar birds, but w m , u

Memorizes Does not memorize Memorizes Does not memorize

Summary of auditory experience Summary of auditory experience

• Females prefer songs of normal > isolate > deaf

at 35 > deaf at 20 days

• Isolation can create two birds of the same

chronological age, but of different learning states

• Enables identification of molecules unique to the

memorizing state

• A similar postponement of sensorimotor learning

can be done (Funabiki & Konishi, 2003)

Neural substrate Neural substrate

Zebra finch brains are sexually dimorphic

HVc

• r

D

Female Male

R D

Female Male

(courtesy of Eugene Akutagawa)

The avian song circuit

HVC HVC HVC

Cortex

HVC HVC HVC

“sing

RA RA RA

Cortex

s g this!”

RA

X

RA

X

RA

to syrinx to syrinx

Motor neurons

to motor neurons

syrinx syrinx

vocal motor pathway vocal motor pathway

neurons controlling the syrinx

The avian song circuit

Cortex

HVC HVC HVC HVC HVC HVC

S triatum

RA

LMAN

RA

LMAN LMAN

RA

“modify!”

RA

X

RA

X

RA

T halamus

DLM DLM DLM

anterior forebrain pathway

Comparison of avian and human circuitry

SONGBIRD

HUMAN Cortex Cortex S triatum S triatum

Area X

T halamus T halamus

Songbird model system Songbird model system

• Vocal learner that captures some of the

Vocal learner that captures some of the complexity of human speech

• Socially-learned and influenced
• Parallel phases and neuroanatomy

p y

• Advantage: Identified circuit
• Advantage: Identified circuit

The KE family

• Deficits in spoken and written language
• Production and comprehension
• Production and comprehension
• Normal non-verbal IQ but low verbal IQ
• Normal peripheral control of orofacial

musculature musculature

• rofacial dyspraxia

Vargha-Khadem et al (1995) PNAS

The basal ganglia is a major site of abnormality abnormality

Frontal view

striatum

Transverse view

striatum

Watkins et al (2002) Belton et al (2003)

FoxP2 - a molecular entry point to language

dimerization DNA binding poly-Q

1 152 209 504 587 715

R553H

1 152 209 504 587 715

• FOX genes are transcription factors, so act by regulating other

molecules molecules

• FOX family members act during embryogenesis
• FOXP2 mutations cause orofacial dyspraxia

Lai, Fisher et al. (2001) Nature

FoxP2 DNA Binding Domain: R553

Working model for FoxP2 in vocal learning

Formation vs function Practice vs performance

Sensory acquisition

60 90 30 120

Sensorimotor learning Maintenance

xP2

?

Fox

?

Sagittal vs. frontal orientation

HVC LMAN X

X X

RA

DLM

D

D

cortex striatum

L

R

thalamus

Detection of ‘gene of interest’

bird 4 slide A slide A GENE GENE mRNA: a a g c c t probe: u u c g g a

Parallel expression of FOXP2 in songbirds and humans

sense

1d zebra finch 22wk human embryo

antisense antisense sense sense antisense antisense sense

Teramitsu, Kudo, Geschwind, White (2004)

Working model for FoxP2 in vocal learning

Formation vs function Practice vs performance

Sensory acquisition

60 90 30 120

2

Sensorimotor learning Maintenance

FoxP2

?

rgets

?

Tar

Adult singing: two behaviors in one Adult singing: two behaviors in one

Directed Undirected

adapted from Hessler & Doupe (1999)

FoxP2 expression in Area X is regulated by the social context of song by the social context of song

Non-singing

mid 3’

Undirected

mid 3’

Directed

mid 3’ mid 3’ mid 3’ mid 3’

nal 1.2 xP2 sign 1.0 alized Fox

Kruskal-Wallis, p < 0.0005 Teramitsu & White (2006)

* *

0.8 Norma

Working model for FoxP2 in vocal learning

Formation vs function Practice vs performance

Sensory acquisition

60 90 30 120

Sensorimotor learning Maintenance

xP2

?

ets Fox

?

Targe

Deafening prior to sensorimotor learning leads to abnormal songs

Tutor Sham-control son (60d) Deafened son (60d)

Motor-driven down-regulation of FoxP2

Control Deaf

Non-singing

Control Deaf

Singing

ratio m

1.2

density r g striatum

1.1

Non-singing vs. singing: p < 0.02, both conditions

ge pixel d X/outlying

1.0

both conditions

Averag Area X

Teramitsu, Poopatanapong, Torrisi & White (2010)

Hearing links song to FoxP2 levels

Hearing Deaf

R2 0 08 0 43 R2 0 7 0 025

tio

1.1 1 0 R2=0.08, p=0.43, ns R2=0.7, p<0.025

xP2 rat

1.0 0 9 1.0

Fox

0.9 0 8 0.9

Amount of singing seconds

200 600 1000 1000 2000 0.8

Amount of singing, seconds

Teramitsu, Poopatanapong, Torrisi & White (2010)

Our working model for FoxP2 in vocal learning

Formation vs function Practice vs performance

Sensory acquisition

60 90 30 120

Sensorimotor learning Maintenance

xP2 ets Fox Targe

FoxP1 expression is sexually dimorphic

medial

sexually dimorphic

♂

medial

HVC LMAN

♂

lateral

RA X LMAN

♂

D

DLM

♀

lateral

F

♀

Teramitsu, Kudo, Geschwind, White (2004)

Assessing the impact of FOXP1 mutations on developmental verbal dyspraxia Vernes, MacDermot, Monaco and Fisher (2009)

"W l d h FOXP1 i "We conclude that FOXP1 mutations are unlikely to represent a major cause of DVD"

A 785kb deletion of 3p14.1p13, including the FOXP1 gene, associated with speech delay, contractures, hypertonia and blepharophimosis

Pariani, Spencer, Graham and Rimoin (2009)

"We feel that a deletion of FOXP1 should be a part of any "It has been suggested that overlap of FOXP1 and FOXP2 expression in the songbird and human brain may indicate that mutation in FoxP1 would also result "We feel that a deletion of FOXP1 should be a part of any differential diagnosis when evaluating a patient with speech delay, developmental delay, blepharophimosis, and y in speech and language abnormalities" arthrogryposis"

Haploinsufficiency of foxp1 is assocated with Chiari I malformation and speech language disorder

Abdul-Rahman, Zimmerman, Justice & Lese-Martin

p g g

, ,

• American Society for Human Genetics meeting, 2008

"Songbird and human fetal brain analysis supports

• verlapping expression of both FOXP1 and FOXP2 in
• verlapping expression of both FOXP1 and FOXP2 in

structures important for learned articulation, which may explain the speech/language phenotype in this patient"

These data could NOT have been obtained in humans

• FoxP2 likely has a post organizational role in learned
• FoxP2 likely has a post-organizational role in learned

vocalizations

• FoxP1 may also be critical for language

FoxP1 may also be critical for language

• Basal ganglia FoxP2 decreases during motor practice,

especially during learning p y g g

• Hearing links FoxP2 to levels of practice
• Birds may ‘self-regulate’ by how often

they practice

Once you're hatched what's it doing? Once you re hatched, what s it doing?

FoxP2 as a 'plasticity gate'

Sensorimotor learning Maintenance

xP2 Fox FoxP2 high or low

Syllables and sequences appear more variable after song practice after song practice

(High Foxp2) Foxp2) (Low Foxp2)

Miller, Hilliard & White (2010)

Sequencing seems more variable after practice NS UD UD UD NS-UD

(High FoxP2)

UD-UD

(Low FoxP2)

Miller, Hilliard & White (2010)

FoxP2 is just the entry point FoxP2 is just the entry point

• FoxP2 targets in humans, songbirds, mice
• Compare gene networks for unique and shared

features

FoxP2 is just the entry point FoxP2 is just the entry point

FoxP2 high or low

?

WGCNA reveals modules of co- expressed genes expressed genes

Hilliard, Miller, Horvath & White, submitted

FoxP2 targets in songbird brain: viral transduction

Pilot data suggest altered gene expression in FoxP2+ cultures altered gene expression in FoxP2 cultures

CNTNAP2 expression is enriched in cortical loops of humans in cortical loops of humans Human Human Rodent

Abrahams et al. (2007)

CNTNAP2 punctuates vocal learning circuitry, similar to humans and unlike rodents

Male Female

Nissl Nissl Cntnap2 Cntnap2

LMAN

Nissl Nissl Cntnap2 Cntnap2

RA

Panaitof, Abrahams, Dong, Geschwind & White (2010)

Disrupt genes in song nuclei using virus

HVC LMAN RA CEREBELLUM DLM DLM T t To motor neurons innervating the syrinx

AAV driven GFP expression in song control region HVC

Our working model for FoxP2 in vocal learning

Formation vs function Practice vs performance

Sensory acquisition

60 90 30 120

Sensorimotor learning Maintenance

xP2 Fox

Next steps Next steps

• Identify zebra finch FoxP2 targets
• Identify zebra finch FoxP2 targets
• Hone in on genes shared with human targets
• Check human data bases for other genes involved in
• Check human data bases for other genes involved in

language disorders

• Characterize expression in songbird

Characterize expression in songbird

• Functional tests on song
• Identify genes related to syllable order

y g y

Acknowledgments

Ik k T it PhD

• Ikuko Teramitsu, PhD
• Amy Poopatanapong, MS
• Sam Torrisi, MFA, MS
• Don Noble, BS
• Carmen Panaitof, PhD
• Austin Hilliard, BS

Austin Hilliard, BS

• Julie Miller, PhD
• Dorsa Beroukhim
• Zach Burkett, BS
• Mike Condro, BS
• Ryan Dosumu-Johnson
• Ryan Dosumu-Johnson
• Jia Liu
• Diana Sanchez

Bird drawing by Johann Ulrich

• Steve Horvath, PhD
• Peter Langfelder, PhD

Thanks

• Alfred P. Sloan

Foundation Foundation

• M.I.N.D. Institute
• Tennenbaum Family

e e bau a y

• National Alliance for

Autism Research

• NIMH, NIDCD
• UCLA
• UQAM
• YOU

YOU