Advanced
Developmental
Psychology
PSY 620P
Messinger
Hmmm…

“Mothers who were pregnant during a 1944 famine in
the Netherlands, for example, were more likely to have
children—and grandchildren—prone to heart disease,
diabetes, and obesity. Female mice that are underfed
during pregnancy also give birth to pups that are more
likely to develop diabetes—and their male offspring have
epigenetic changes in their sperm. The offspring of those
males are also prone to diabetes. Male rats that are overfed,
when mated with healthy females, also had offspring that
were prone to developing diabetes.”
•
http://www.sciencemag.org/news/2015/12/weight-gain-and-loss-can-alter-men-s-sperm
Messinger
Obesity and Bariatric Surgery
Drive Epigenetic Variation of
Spermatozoa in Humans
Donkin, I., Versteyhe, S., Ingerslev, L. R., Qian, K., Mechta, M., Nordkap, L., . . .
Barres, R. (2015). Obesity and Bariatric Surgery Drive Epigenetic Variation of
Messinger
Spermatozoa in Humans. Cell Metab. doi: 10.1016/j.cmet.2015.11.004
Which is better?
Messinger
Environmental Influences on Gene
Activity

In rodents:
–
–

Low maternal care  elevated methylation
Prenatal exposure to chronic stress  increased
methylation
Less nurturing mothering leads to poorer stress
response in rat pups
 Fewer
corticosterone receptors
 Linked to DNA methylation
 Enzymes reverse methylation, improve receptor
numbers
–
Szyf & Meany (2004)
Gangi
Imagine you have access to a library…
1 DNA Sequence = 1 Book
(Champagne & Mashoodh, 2009; Syzf & Bick, 2012)
Rumper



DNA transcription: the process of DNA being
read by an enzyme called RNA polymerase >
leading to the production of mRNA > which is
then translated into a protein
DNA methylation: one type of epigenetic
mechanism; reduces the accessibility of DNA
and can lead to “silencing” of the gene
Epigenetic influences do NOT alter the sequence
of DNA
(Champagne & Mashoodh, 2009; Syzf & Bick, 2012)
Rumper
Epigenetic
mechanisms


Histone acetylation tends to
promote gene activity
Histone methylation and
DNA methylation tend to
inhibit it.
Messinger
How can an organism have different cell
types yet one genome?
 “The idea that DNA function could be
stably diversified without changing the
sequence comes from the study of cellular
differentiation during embryonal
development.” (Szyf & Bick, 2012)

Messinger
DNA methylation pattern
Szyf & Bick, 2012
Messinger
Dynamic DNA methylation
Messinger
Szyf & Bick, 2012
DNA methylation adaption are system wide
and involve multiple gene circuitries
Messinger
Why some books are read and
others not?
How could epigentetics play a
role in your research?
Rumper
Global Epigenomic Reconfiguration During Mammalian
Brain Development (Lister et al., 2013)
Background
• Early postnatal burst of synaptogeneis  activity-dependent pruning of
excess synapses during adolescence
 This process forms the basis for experience-dependent plasticity
 Disruption leads to behavioral alterations & neuropsychiatric disorders
• Epigenome: Network of chemical compounds surrounding DNA that modify
genomic expression without altering DNA sequences
 Dynamic epigenetic changes occur during brain development,
maturation, & learning
 DNA METHYLATION PLAYS KEY ROLE:
Major transcriptional changes  adult electrophysiological
characteristics in neocortical neurons
Goals of the Article
Better understand the unique role of DNA methylation in brain
development and function  Unravel the genetic program and
experience-dependent epigenetic modifications leading to a fully
differentiated nervous system
Methods: Integrate empirical data of genome-wide composition, patterning,
cell specificity, and dynamics of DNA methylation at single-base resolution in
human & mouse frontal cortex at different developmental stages
Global Epigenomic Reconfiguration During Mammalian
Brain Development (Lister et al., 2013)
Types
1. mCG
2. mCH
(where H = A, C, or T)
• DNA methylation is a stable covalent modification that
persists in post-mitotic cells throughout their lifetime,
helping define their cellular identity
Key Findings
1. CH methylation accumulates in neurons through early
childhood & adolescence – becoming the dominant form of
DNA methylation in mature human neurons
Demonstrates large-scale
reconfiguration of neuronal
epigenome!
A word on identity
1.Amy M. Boddy, Angelo Fortunato,
Melissa Wilson Sayres, Athena
Aktipis. Fetal microchimerism
and maternal health: A review
and evolutionary analysis of
cooperation and conflict beyond
the womb.BioEssays, 2015;
DOI: 10.1002/bies.201500059
Messinger
Schizophrenia risk from complex
variation of complement component 4
a person's risk
of
schizophrenia
is increased if
they inherit
specific
variants in a
gene related to
"synaptic
pruning“
C4 structures, C4A expression, and schizophrenia risk
http://www.sciencedai
ly.com/releases/2016/
01/160127141400.ht
m
A Sekar et al. Nature 1–6 (2016) doi:10.1038/nature16549
Methods in Developmental
Neuroscience

Direct Assessments
–
–
–

EEG/ERP
Functional Magnetic Resonance Imaging (fMRI)
Near Infrared Spectroscopy (NIRS)
Indirect Assessments
–
Marker Tasks
EEG/ERP Assessments
The EEG signal

Baseline/Resting
EEG
–
–
Ongoing EEG-summation of all
electrical activity
occurring in the
brain at a given
moment
Frequency
distributions -indicators of state
(sleep/wake) and
trait (arousal)
marker
Event-Related Potentials (ERPs)

EEG data is timelocked to a specific
stimulus or event and
then averaged
–
Averaging allows
filtering of
unrelated/background
EEG
Development
Brain Development

Activity-dependent specialization –
–
Face Processing example
 N170
to faces becomes specialized for upright faces by
12 months; prior to that elicited to inverted and upright
(de Haan et al., 2002; Halit et al., 2003)
MRI

Uses magnet and
radio waves to image
bodily tissues
–
–
Structural
Functional
Intellectual ability & cortical development
(structural)

IQ group and change in cortical thickness
(Shaw et al., 2006)
Intelligence and changes in cortical
thickness

Superior minus average intelligence groups
(Shaw et al., 2006)
Brain Development
 More
distributed pattern of activation in children vs.
adults during face matching task (functional)
From Passarotti et al., 2003
Dynamic Reconfiguration of Structural and Functional
Connectivity Across Core Neurocognitive Brain Networks
with Development. Uddin, et al., 2011


’Right fronto-insular cortex
(rFIC) is a component of a
salience network (SN)
mediating interactions between
large-scale brain networks
involved in externally oriented
attention [central executive
network (CEN)] and internally
oriented cognition [default
mode network (DMN)].
The causal influence of the
rFIC on nodes of the SN and
CEN was greater in adults than
children.
Near infrared spectroscopy
(NIRS)

Infrared light illuminates
tissue and activity below skin

Wavelengths of light scatter in
tissue and are absorbed
differently depending on
oxygen level (= activity)
NIRS

Figure 4. A single near-infrared spectroscopy (NIRS) channel over
prefrontal cortex from Nakano et al. (2009) showing decreasing
activations in 3 blocks of 5 trials to a speech category, following by
recovery to a novel speech category (orange) in the 4th block but not to a
no-change control group (green). Hb haemoglobin. From “Prefrontal Cortical
Involvement in Young Infants’ Analysis of Novelty”, by T. Nakano, H. Watanabe, F. Homae, and G. Taga, 2009,
Cerebral Cortex, 19, pp. 455–463. Copyright 2009 by permission of Oxford University Press.
Messinger
Four levels of brain development
From Nelson, 1999
Neural tube formation and
differentiation
https://www.youtube.com/watch?v=lGLexQR9xGs (1:49)
Bloom, Nelson, & Lazerson, 2001
Overview



Increasing
differentiation of areas
of cortex
Infant is born during
height of brain
development
Tertiary sulci develop
from 1 month before
to 12 months after
birth
http://www.youtube.com/watch?v=YXTA0lUBZW4 1:20-2:19
https://www.youtube.com/watch?v=86NDMfxU4ZU structural view
Neural migration



Many elements of initial neural migration
specified genetically
By 20 weeks gestation, 100 billion neurons!
 50,000 – 500,000 neurons per minute
Neurons follow path of glial cells outward from
ventricles
–
To form 6 layers of cortex
Time lapse sequences


Neuron migration
Radial migration (glial guidance) and somal
translocation
–

http://www.nature.com/neuro/journal/v4/n2/ext
ref/nn0201-143-S1.mpg
Typical and Atypical
http://www.youtube.com/watch?v=GBIa8G
3gBH0&feature=related
Proliferation & migration of neurons

General pattern of brain development genetically
specified
–
–
–

By 20 weeks, most neurons present
3rd - 16th prenatal week most crucial
At 8 weeks, head is half of fetus
But specific connections depend on generic
growth processes and sensory-motor stimulation
–
–
Trillions of connections still forming
Trimming of these connections is developmental task
Neural development: Synaptogensis

Once in place, synapses are overproduced
somewhat haphazardly
–


1 year old has 150% more synapses than adult
These are pruned (diminish) during development
Repetition of sensory-motor patterns create more
specific set of experience dependent synaptic
linkages
Changes in Synaptic Density
Like a
growing
forest
Increase in complexity of neural
connections
Does
increasingc
omplexity
asymptote?
How do the correct synapses form?

15,000 synapses for every cortical neuron
–
1.8 million per second in first 2 years!



Cerebral cortex triples in thickness in 1st year
Sensory and motor neurons must extend to correct
brain are and form correct synapses
This quantity of information cannot be genetically
micro-managed
–
Edelman
Synaptic Density Growth Curves
See ThompsonSchill et al.
(2009) for
interesting
Discussion of
benefits of
Protracted PFC
development
Functional regressions in
face perception
(Pascalis, de Haan, & Nelson, 2002)
Prolonged pre-specialization period
supports plasticity
–
Extent of plasticity depends on age at injury, site
of damage, skill area
 Early
injury ( < 6 mos) to either hemisphere affects
language competence, rapid improvements by 5 yrs with
compensatory activation (Stiles et al., 2001)
 Greater
spatial impairments with effects differing on
hemispheric damage
 Sleeper
effects
Increasing specialization has
functional implications
- Examples of functional regressions
 Face
–
perception (Pascalis, de Haan, & Nelson, 2002)
By 9 months lose ability to discriminate monkey faces as well
as human faces
 Phonemic
–
discrimination (Werker & Polka, 1993)
Young infants discriminate all phonetic contrasts (regardless of
native language) but only up until 12 months of age
Brain Development

Differentiation of Cerebral Cortex
–
Reflection of innate modularity or experiencedependent processes?
 Adults
tend to have similar functions housed within
same regions of cortex
–
–
Does this imply innateness?
Likely a combination of both
 Generic
large scale regions with functional
specialization dependent on activity
Cortical Expansion
Similar patterns of cortical expansion
between infants and adults as between
macaque monkeys and adults
 “The pattern of human evolutionary
expansion is remarkably similar to the
pattern of human postnatal expansion”

–
(Hill et al., 2010)
Bell
Comparing evolutionary and postnatal
cortical surface expansion
(A) Map of regional
evolutionary cortical
expansion between an
adult macaque
and the average human
adult PALS-B12 atlas
(right hemisphere only).
Evolution expansion
scale indicates how
many times larger the
surface area is
in humans relative to
the corresponding area
in the macaque.
(B) Map of human
postnatal cortical
expansion (combined
left and right
hemispheres)
for comparison.
(C) Correlation map
comparing postnatal to
evolutionary cortical
surface expansion.