Neurodevelopment,

the tricky journey to reaching a

functional neural network

Albane CLAVERE, Celia REYNAUD, Gabriela D. B.

MONTICELLI, Juliette LE LIVEC, Maële VIANFE

APP 9 supervised by:

V. Matarazzo
 Physiological Cognitive

Behavioral

Epilepsy Autism

Network activity Neuro

disruption development
Neurodevelopment

Cellular proliferation Neuronal maturation

Germinal layers Cellular migration Neuronal network

Table of Contents

01 Clinical aspects 02 Neural Networks

Cellular
03 Domain
04 Conclusion
 01.
Clinical Aspects
Observation of neuropathological cases

BY-SA.
01. Clinical aspects
First observations and questions

Early Onset Epileptic Encephalopathy

● Age: 1th – 8th week
● Symptomes: Seizures
● No seizures past the second month
● Diagnosis: EEG and genome sequencing
01. Clinical aspects
Pathophysiology of the EOEE

Opening of
voltage gated K+
channels

Genetic Mutations

• Genes involved in the process of

vesicle release

• Genes coding for voltage-dependent

sodium and potassium

Kv7.2 channel
● IM current
01. Clinical aspects
Prognosis of the EOEE

Does the channel

DNA
work?

Functional Channel
Healthy child

Partially Functional Channel

Healthy Child ?

Disfuctional Channel
Polyhandicap
Mental Retardation
Normal EEG – Premature Baby
01. Clinical aspects
Normal EEG - Delta Brushes

Twitches Thalamo cortical Loop

 The Significance of the Twitch

Endogenous sensory
information

Internal representation Pathology

Healthy baby

Network ready for

exogenous stimuli
Abnormal EEG – KCNQ2 Baby
 01. Clinical aspects
Pathophysiology of the EOEE

Is the cognitive disorder caused

should we prioritize anti-
by the seizures or the mutation ?
epileptic treatment or not?

Clinical research is
not sufficient to answer

despite the side effects ?

 02.
Neural networks
Understanding
neuropathological cases
02. Neural Networks
Two animal models

+ +
Mutation Seizures Mutation Seizures

Cognitive disorders? Cognitive disorders?

 02. Neural network
Connectivity

Laser Scanner Photostimulation

(LSPS)

Loose patch configuration

Embryo brain slice

Glutamate uncaging
02. Neural network
Connectivity

WISTAR Layers
genotype
Age P14 P30
1,4,5,6

Connectivity strength

somatosensory cortex

GAERS Layers
genotype Age P14 P30
1,4,5,6
WISTAR → Control group
GAERS → Epileptic group
02. Neural network
Connectivity

Size of EPSCs and IPSCs in WISTAR and GAERS

• P14 : Weaker currents in GAERS

compared to WISTAR

• P30 : Stronger currents in GAERS

compared to WISTAR

Decrease in connectivity

Increase in excitability
02. Neural network
Early electrical activities

GDP SPA

SPECIFIC
NEURONAL SHAPING OF
ELECTRICAL
MIGRATION SYNAPSES
ACTIVITIES

SPA (Synchronous Plateau Assemblies) GDP (Giant Depolarizing Potential)

02. Neural Networks
Results

Proportion of active cells with GDP activity by age Proportion of active cells with SPA activity by age
02. Neural Networks
Results

Comparison of the proportion of active cells

with GDP or SPA activity
 03.
Cellular
domain
Impact of external factors
on neuronal networks’ growth
03. Cellular domain
Protocol

Sampling of Cultivation
E17 embryo cortex for 3 days in 4 conditions
With dissecting microscope Control / NGF / 10µMpesticide /
50 nM pesticide

Neurobasal 2 plates/ condition

Mouse embryo 37°C for 3 days
Medium
03. Cellular domain
Protocol

Immuno-histochemistry Imaging
AC1 MAP2 + AC2 anti-AC1 Alexa 488 With a ZEISS 2 Apotome
 observations
Pesticide 50nM CONTROL
 observations
Pesticide 10µM CONTROL
NGF CONTROL
03. Cellular domain
Results
04. Conclusion

Stable and functional

Epilepsy
;

Autism ?
 THANKS!
To
all this amazing people

Mr Valéry Matarazzo Mme Ingrid Bureau Mr Matthieu Mihl Mr Pierre Pascal

Our Supervisor Lenck-Santini
THANK
YOU
for listening !
Words of wisdom
From the INMED’s hallway

Der Neptun ist der sonnenfernste Planet

- Un élève de CM2
 ReferencesWords of wisdom

- Bender AC, Natola H, Ndong C, Holmes GL, Scott RC, Lenck-Santini PP. Focal Scn1a knockdown induces cognitive
impairment without seizures. Neurobiol Dis. 2013;54:297-307. doi:10.1016/j.nbd.2012.12.021
- Pierre-Pascal Lenck-Santini. Bad Timing for Epileptic Networks: Role of Temporal Dynamics in Seizures and
Cognitive Deficits. Epilepsy Currents, Wiley, In press, pp.153575972110018. ⟨10.1177/15357597211001877⟩.
⟨hal-03190547⟩
- Bender AC, Luikart BW, Lenck-Santini P-P (2016) Cognitive Deficits Associated with Nav1.1 Alterations:
Involvement of Neuronal Firing Dynamics and Oscillations. PLoS ONE 11(3):
e0151538.doi:10.1371/journal.pone.0151538
- Shepherd GM, Stepanyants A, Bureau I, Chklovskii D, Svoboda K. Geometric and functional organization of cortical
circuits. Nat Neurosci. 2005 Jun;8(6):782-90. doi: 10.1038/nn1447. Epub 2005 May 8. PMID: 15880111.

- Bureau I, Shepherd GM, Svoboda K. Precise development of functional and anatomical columns in the
neocortex. Neuron. 2004 Jun 10;42(5):789-801. doi: 10.1016/j.neuron.2004.05.002. PMID: 15182718.
Références?
ZIELE DES MEETINGS

NEPTUN MARS
Der äußerste Planet Obwohl er rot ist, ist der Mars
unseres Sonnensystems! sehr kalt

MERKUR JUPITER
Der Merkur ist der kleinste Jupiter ist der größte Planet
Planet des Sonnensystems des Sonnensystems
 ÜBER DAS
PROJEKT
Hier kannst du eine kurze Beschreibung des Themas geben,
über das du sprechen möchtest. Wenn du zum Beispiel über
den Merkur sprechen willst, könntest du sagen, dass er der
kleinste Planet im gesamten Sonnensystem ist
PROJEKTZEITPLAN

WOCHE 1 WOCHE 2 WOCHE 3 WOCHE 4

PHASE 1
Task 1

Task 2

PHASE 2
Task 1

Task 2
UNSER CHECKLIST

SCHREIBE HIER FERTIG

Der Merkur ist der sonnennächste Planet

Die Venus ist ein Gesteinsplanet

Der Mars ist eigentlich sehr kalt

Jupiter ist der größte Planet in unserem Sonnensystem!

NOTIZEN
Die Venus hat einen schönen Namen und ist der ist der drittkleinste Planet
des ganzes Sonnensystems
KPI DASHBOARD

VENUS
Die Venus ist fast so groß wie
die Erde

MARS
Obwohl er rot ist, ist der Mars
sehr kalt Folge dem Link in das Diagramm, um die Daten zu ändern
und füge dann das neue hier ein

$35,000 30 TAGE 7 ORTE 77

Normaler Preis Laufzeit Unsere Filiale Lagerbestände
STATUS REPORT

PRODUKT BESCHR. STATUS

Merkur ist der sonnennächste

TASK 1 Merkur
Planet
35 %

Die Venus ist extrem warm,

TASK 2 Venus
wärmer als Merkur
40 %

Obwohl er rot ist, ist der Mars

TASK 3 Mars
sehr kalt
18 %
RAID SUMMARY

RISK ASSUMPTIONS
Der Merkur ist der Die Venus ist der zweite
sonnennächste Planet und der Planet des Sonnensystems und
kleinste der drittkleinste

ISSUES KPIs
Obwohl er rot ist, ist der Mars Saturn ist ein Gasriese und hat
sehr kalt. Er enthält viel viele Ringe. Er besteht aus
Eisenstaub Wasserstoff
 WIR SIND WIR WOLLEN HIER
HIER SEIN
Der Merkur ist der sonnennächste Die Venus hat einen schönen
Planet und der kleinste im Namen und ist der zweite Planet
Sonnensystem. Der Name dieses von der Sonne. Sie ist fast so groß
Planeten hat nichts mit dem wie die Erde. Die Venus ist das
flüssigen Metall zu tun zweithellste Objekt des
Sonnensystems
 15% 50%
Die Venus ist das Jupiter ist der größte
zweithellste Planet Planet von allen

25% 75%
Saturn ist ein Gasriese Merkur ist der kleinste
mit Ringen Planet
Slides // 20XX

150,000
Der Neptun ist der sonnenfernste Planet
EIN BILD SAGT MEHR ALS TAUSEND WORTE
UPCOMING EVENTS

23/07/2022 21/08/2022
Der Jupiter ist ein Gasriese und der Jupiter ist der größte aller Planeten in
größte Planet des Sonnensystems the Solar System

18/09/2022 23/11/2022
Saturn ist ein Gasriese mit Ringen. Er Der Merkur ist der sonnennächste Planet
besteht aus Wasserstoff und der kleinste

15/12/2022 13/02/2023
Die Erde ist der dritte Planet von der Der Neptun ist der sonnenfernste Planet.
Sonne aus gesehen Er ist wirklich größ
HIER HAST DU EINE KARTE

MARS
Obwohl er rot ist, ist der
Mars sehr kalt. Er enthält viel
Eisenstaub
DESKTOP
MOCKUP
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Werk ersetzen. Rechtsklick
einfach darauf und wähle „Bild
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Slides // 20XX

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Neuron
Infographics
Here is where this template begins
 Neuron infographics

Sensory Motor
Jupiter is a gas giant and Neptune is the farthest
the biggest planet planet from the Sun

Pyramidal Astrocyte
Mercury is the closest Despite being red, Mars
planet to the Sun is a cold place

Betz cell Microglia

Venus has a beautiful Pluto is considered a
name but is hot dwarf planet
 Neuron infographics

01

Sensory neurons
Mercury is the closest
planet to the Sun 02

Motor neurons
Venus has a beautiful
03 name but is hot

Interneurons
Jupiter is a gas giant and
the biggest planet
Neuron infographics

Cell body
01 Mercury is the closest
planet to the Sun

Nucleus
02 Venus has a beautiful
name but is hot

Axon
03 Jupiter is a gas giant and
the biggest planet
 Neuron infographics

01 02

Jupiter Neptune
Jupiter is a gas giant and Neptune is the farthest
the biggest planet planet from the Sun

03 04

Mercury Mars
Mercury is the closest Despite being red, Mars
planet to the Sun is a cold place
 Neuron infographics

01 02

Jupiter Neptune
Jupiter is a gas giant and Neptune is the farthest
the biggest planet planet from the Sun

03 04

Mercury Mars
Mercury is the closest Despite being red, Mars
planet to the Sun is a cold place
 Neuron infographics
Sensory neuron

Dendrites

Peripheral process

Axon

Unipolar neuron Cell body Central process

Mercury is the closest planet to the

Sun and the smallest one in the entire
Solar System
 Neuron infographics
Dendrite Axon terminal
Jupiter is a gas giant and Neptune is the farthest
the biggest planet planet from the Sun

Nucleus Node of Ranvier

Mercury is the closest Despite being red, Mars
planet to the Sun is a cold place

Cell body Schwann cell

Venus has a beautiful Pluto is considered a
name but is hot dwarf planet

Axon Myelin sheath

Earth is the third planet Ceres is located in the
from the Sun main asteroid belt
 Neuron infographics
01 02 03

Sensory Pyramidal Betz cell

Jupiter is a gas giant and Mercury is the closest Venus has a beautiful
the biggest planet planet to the Sun name but is hot
 Neuron infographics

Synapses
Mercury is the closest 01
planet to the Sun

Excitatory
Venus has a beautiful 02
name but is hot

Inhibitory
Jupiter is a gas giant and 03
the biggest planet
 Neuron infographics

The structure
of microglia
Cell body

Nucleus

Microglyocyte
Mercury is the closest planet to
the Sun and the smallest one in
the entire Solar System
 Neuron infographics

Motor
01 Neptune is the farthest
planet from the Sun

Astrocyte
02 Despite being red, Mars
is a cold place

Microglia
03 Pluto is considered a
dwarf planet
 Neuron infographics
Sensory neuron

Physical inputs Chemical inputs

● Light ● Smell
● Sound ● Taste

Jupiter is a gas giant and

Response the biggest planet
 Neuron infographics
Located within the fifth
Betz cell Giant pyramidal cells
layer of the grey matter
Pyramidal cells of Betz

Primary motor
cortex
 Neuron infographics

Soma Dendrites
Jupiter is a gas giant and 01 02 Neptune is the farthest
the biggest planet planet from the Sun

Axon Axon terminals

Mercury is the closest 04 03 Despite being red, Mars
planet to the Sun is a cold place
 Neuron infographics

50% 70%
Soma Dendrites
Jupiter is a gas giant and Neptune is the farthest
the biggest planet planet from the Sun

80% 60%
Axon Axon terminals
Mercury is the closest Despite being red, Mars
planet to the Sun is a cold place

Follow the link in the graph to modify its data and then paste the new one here. For more info, click here
 Neuron infographics
80%
Motor
Neptune is the farthest
planet from the Sun
60%

Astrocyte
Despite being red, Mars
is a cold place

30%
Microglia
Pluto is considered a
dwarf planet
 Neuron infographics

30% 20%
Soma Dendrites
Jupiter is a gas giant Neptune is very far
and the biggest planet from the Sun

40% 10%
Axon Axon terminals
Mercury is the closest Despite being red, Mars
planet to the Sun is a cold place

Follow the link in the graph to modify its data and then paste the new one here. For more info, click here
 Neuron infographics

Pyramidal cells Location Cerebral cortex esp. Layers III and V

Shape Multipolar Pyramidal

Function Excitatory projection neuron

Pyramidal cells are a type of multipolar Neurotransmitt Glutamate, GABA

neuron er
 Neuron infographics
Cell body
Jupiter is a gas giant and 40%
the biggest planet

Myelin sheath
Mercury is the closest 20%
planet to the Sun

Schwann cell
Venus has a beautiful 10%
name but is hot

Axon terminal
Earth is the third planet 30%
from the Sun
 Neuron infographics
Synapses Neuron
Input 1
Neptune is the farthest 01
planet from the Sun

Input 2
Despite being red, Mars 02
is a cold place

Input 3
Pluto is considered a 03
dwarf planet

Output
 Neuron infographics

Synapses
01 Mercury is the closest
planet to the Sun

Excitatory
02 Venus has a beautiful
name but is hot

Inhibitory
03 Jupiter is a gas giant and
the biggest planet

Follow the link in the graph to modify its data and then paste the new one here. For more info, click here
 Neuron infographics

Soma Axon

Dendrites Myelin

Synapse
Despite being red, Mars
is a cold place
 Neuron infographics

75% 25% 40%

Betz cell Astrocyte Microglia

Mercury is the closest Despite being red, Mars Jupiter is a gas giant and
planet to the Sun is a cold place the biggest planet
 Neuron infographics

Excitatory
Venus has a beautiful
name, but it’s hot

Synapses
Mercury is the closest
planet to the Sun

Inhibitory
Jupiter is a gas giant and
the biggest planet
 Neuron infographics

Sensory neurons
Mercury is the closest
planet to the Sun

Interneurons
Jupiter is a gas giant and Response
the biggest planet

Motor neurons
Venus has a beautiful
name but is hot
 Neuron infographics
50% 70%
Soma Dendrites
Jupiter is a gas Neptune is the
giant and the farthest planet
biggest planet from the Sun

80% 60%
Axon
Axon
terminals
Mercury is the Despite being red,
closest planet to Mars is a cold
the Sun place

Follow the link in the graph to modify its data and then paste the new one here. For more info, click here
 Neuron infographics

Communicating axosomatic Mercury is the closest

synapses planet to the Sun

Synapse Communicating axodendritic Jupiter is a gas giant and

s synapses the biggest planet

Communicating axoaxonic Venus has a beautiful

synapses name but it’s hot
 Neuron infographics

Sensory neurons 75 Motor neurons 50

Jupiter is a gas giant and Neptune is the farthest
the biggest planet % planet from the Sun %
Central nervous system Neuron infographics

01 02 03

Sensory input Neural processing Motor output

Despite being red, Mars Jupiter is a gas giant and Neptune is very far from
3 step process is a cold place the biggest planet the Sun
 Neuron infographics
Microglia
Pluto is considered a
dwarf planet Regulate brain development

Resident cells Maintenance of neuronal networks

of the brain

Injury repair
 Types of neurons
Neuron infographics

Despite being red, Mars

is a cold place 80% 50% 60% 90% 70% 30%

Follow the link in the graph to modify its data and then paste the new one here. For more info, click here
 Neuron infographics

80%

70%

60%
Microglia
Jupiter is a gas giant and
the biggest planet

Follow the link in the graph to modify its data and then paste the new one here. For more info, click here
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