1

The Nervous System

Nobuhiko YamamotoOsaka UniversityGraduate Sch Frontier Biosciences

Basic aspects in the nervous system

2

A neuron is composed of axon, dendrite and somata

Diversity of neurons

3

Generation and conduction of action potentials

Occurrence of action potentials with sodium and potassium channels

4

Extracellular recording

+- -+

EPSP and IPSP

Excitatory postsynaptic potential

inhibitory postsynaptic potential

5

+-

EPSC recorded by patch recording

Excitatory postsynaptic current

I = C*dV/dt + V/R

6

Ionotropic and Mebotropic receptors

Function of the Brain

7

Functional properties of the nervous system１．Intensity is represented by frequency of action potentials

ex, response of retinal ganglion cells to light stimuli, response of motor cortical neurons to force

２．Different modality is processed in different brain region.The presence of visual, auditory, somatosensory, and motor areas

３．Topology is present.ex, retinotopy, somatotopy

４．Reciprocal innervation produces precise control.ex, flexor and extensor

５．Hierarchy of information processing is essential for selective responses.ex. Dotted light stimulus for retinal ganglion cells, more complex visual stimuli for cortical cells

What does firing code?

8

Cerebral cortexmotor

association

Somatosensoy

auditory

visual

Broadmann

コラム構造 (columnar structure)

Hubel and Wiesel

Tootel et al., 1982

Macaque retinotopyOcular dominance columnOrientation column

9

Body representation

Orientation column

Blasdel

10

Optical images in the higher visual cortex

Tanifuji et al., 2001

Myotatic reflex ( Ia afferent)

11

Synergists and antagonists

Reflex of cutaneous and deep receptors

12

Development of the Brain

Development of Human Brain

13

Establishment of neuronal circuitries

cell proliferationmigrationfate determinationaxon outgrowthpath-findingtarget recognitionsynapse formation

Cell division

14

Neural stem cells and neuronal cells

影山龍一郎紹介 in 新学術newsletter

proneural gene

nucleus

cytoplasm

neuron

cleavage of cytoplasmic region

neural stem cell

neuralstem cell

neuron

Desai and McConnell, 2000

Cell division and migration

15

From John Parnavelas

Cell migration of inhibitory neurons

Cell fate determination

Intrinsic factors(transcriptional factor)

Cell fate

Extrinsic factors(extracellular signals)

Differentiation

16

Patterning centers and graded transcription factors drive arealization of the neocortex

O’leary and Sahara, 2008

Fukuchi-Shimogori and Groove, 2001

Electroporatedsite

Neocortex Patterning by the Secreted Signaling Molecule FGF8

17

Emx2 expressionHamasaki et al., 2004

Armentano et al., 2007

Axon growth and guidance

18

Axon guidance mechanism

Guidance by attractive factors

By repulsive factors

Cellular responsiveness

19

Diffusible factors attract growth cones

Commissural axon system

20

Semaphorin is involved in the formation of spinal refelex pathway

21

Retinotectal projection

posterior

anterior

lateral

medial

nasaltemporal

dorsal

ventral

Fujisawa et al., 1987

Dorsal Lateral Ventral Medial

Retinotopic map formation in the tectum

Temporal Anterior Nasal Posterior

22

Stripe assay

Ephrin-Eph system regulates retinotectal projections

23

Refinement by neuronal activity

WT

β2 KO

Patterned activity is necessary for fine map formation

McLaughlin et al., 2003

24

Sretavan et al., 1988

Neural activity is necessary for pruning of axon branching

Huberman et al., 1988

Neural activity is necessary for segregation of RGC axons in the LGN

P1 P10 P10, epibatidine

25

Plasticity

Hippocampus

26

Long-term potentiation in hippocampal circuitry

Possibility for postsynaptic mechanisms for LTP

27

Hubel and Wiesel, 1962

Ocular dominance column after monocular deprivation

Constantine-paton and Low, 1978

Eye-specific bands are formed by environmental control

28

Orientation responsiveness

Axonal branching and synapse formation are inhibited when electrical activity is blocked

Uesaka et al., 2007

29

Zuo et al., 2005

Morphology of dendritic spines also changes even in the adult

神経修復と神経再生

Repair and Regeneration

30

Christopher Reeve

頚髄における皮質脊髄路の対側への軸索枝形成

0

2

4

6

8

10

12

14

16

C4 C5 C6 C7 C8

cont

rala

tera

l / ip

sila

tera

l (%

)

42 daycontrol BDA

100μm

injury

CST

cervical spinal cord

BDA BDA

control42 day

**

* *

**

皮質脊髄路の再交叉

31

V

VI

VII

VIII

X

BDA

脳損傷後に再交差した皮質脊髄路の枝はlamina VII とVIII に投射する

C4

Propriospinal neuronはlamina VII とVIII に局在する

long

short

0

10

20

30

40

50

60

I-III IV V VI VII VIII IX Xlamina

42day (C4 level)

9週齢で運動皮質切除

3日齢で運動皮質切除

幼い時は代償性神経回路の形成が著明