Neocortex: consciousness

Cerebellum: unconsciouscontrol of posture & movement

Grey matter(chips)

White matter(the wiring: the brain mainly talks to itself)

brains

1. Golgi-stained section of cerebral cortex 2. One of Ramon y Cajal’s faithful drawingsshowing nerve cell diversity in the brain

cajal

Neuropil: perhaps 1 km2 of plasma membrane - a molecular reaction substrate for 1024

voltage- and ligand-gated ion channels.

light to

Glia: 3 further cell types

astros

1. Astrocytes: trophic interface with blood, maintain blood brain barrier, bufferexcitotoxic neurotransmitters, support synapses

oligos

Oligodendrocytes:myelin insulation

Production persists into adulthood:radiation myelopathy

3. Microglia: resident macrophages of the CNS. Similarities and differences withLangerhans cells, the professional antigen-presenting cells of the skin. 3% of all cells, normally renewed very slowly by division and immigration.

Normal Neurosyphilismicroglia

Cell birth

Migration

Neurite outgrowth

Synaptogenesis

Myelination

Synapse elimination

week: 0 6 12 18 24 30 36 Month: 0 6 12 18 24 30 36 Year: 4 8 12 16 20 24

EMBRYONIC POSTNATAL

Modified from various sources inc:Andersen SL Neurosci & Biobehav Rev 2003Rakic P Nat Rev Neurosci 2002Bourgeois Acta Pediatr Suppl 422 1997

Most adult neurons are already produced by birth

Peak synaptic density by 3 months

timeline

2*

1*

*1 Synaptogenesis Rat

Cat

Macaque

Man

DEA

TH

DEA

TH

DEA

T H

DEA

T H

100%

0%

BIR

TH

BIR

TH

BIR

TH

BIR

TH

PUB

ERTY

PUB

ERTY

PUB

ERTY

PUB

ERTY

100%

100%

100%

0%

0%

0%

10 days 100 days 2.5 years 25 years

Density of synapses inprimary visual cortexat different times post-conception.(logarithmic scale)

The density values equivalent to 100% vary between speciesbut in Man the peak value is 350 x106 synapses per mm3

The peak rate of synapse formation is at birth in themacaque: extrapolating tothe entire cortex, this amounts to around 800,000 synapses formed per sec.

(Modified from Bourgeois, JP,Acta Pediatr Suppl. 422: 1997)

synapse density

Plasticity in the adult cerebral cortex: phantom limbs.

Referredphantomhands

These phenomena could be explained if cortical afferents (blue) sprout new connections (red to occupy the vacated sensory field, but the timescale is too short. There may be more widespread (but latent) cortical connectivity than we are accustomed to believe.

Ramachandran

Myelination continues through the 2nd decade in some regions

There is evidence that axons cannot myelinate until they form synapses, so theschedule may reflect gradual acquisition of hard-wired status.

myelin schedule

* 2. The hippocampus: site of transfer of declarativememories from short term into longterm storage in the neocortex.

Dentate gyrus: 1 of 2 significant sites of neurogenesis in the adult brain

Hippocampus

Dentate gyrus

hippocampus

Neurogenesis in the adult rat dentate gyrus

2 million granule neurons in the adult rat

About 10,000 new granule neurons produced per day, ie, 0.5% of total.

New granule cells differentiate as proper neurons butonly survive for about 1m. May compete for survival or have a specific transient role.

Rate of division enhanced by environment enrichment,activity & learning.

Reduced by stress & steroids and no doubt affected by hormones during puberty.

Sources include:Cameron & McKay, J Comp Neur 2001Gould E, et al, Nature Neuroscience 2001Shors, TJ et al, Nature 2001Monje M & Palmer T, Curr Op Neurol 2003 Modified from Cameron & McKay

J Comp Neur 2001rat dentate

The mitotic dance in the early neuroepithelium: exponential growth

Cell cycle time ... 7hrsEarly spinal cord

Cell numbers in Man: cerebral cortex 15 billioncerebellum 70 billionother 5 billion

In the macaque, all cortical neurons are produced in 2 months between E40 & E100,during which the average rate of production is 3000.sec-1

neurogenesis 1

Later development: linear growth by unequal divisions producing 1 post-mitotic neuroblast (dark blue) and 1 renewed stem cell (light blue)

1

2

ventriculargerminalzone

ventricleneurogenesis 2

Vascular niches in the hilus of the dentate gyrus support adult neurogenesis

Therapeutic cranial X-irradiation halts the production of neurons, but this is aninflammatory effect. Il-6 made by microglia switches the fate of the dividing stemcells from neurons to glia.

stem cell

neuroblasts

new granuleneuron

NORMAL

new astrocyte

glioblastsmicroglia

STRESSED

Sources include: Alvarez & Lim Neuron 2004Kemperman & Neumann Science 2003

niches

Childhood development of the CNS

At 9 months, the computer rolls off the production line apparently complete.We have a fair understanding of the mechanics of assembly, but very little idea of what happens while the software is installed during the ensuing 24 years.

Stages in cognitive development have been defined,but we have almost no mechanistic understanding of what they entail.

Science can respond to social priorities. Much of what we know about the production line arose from shock at the consequences for the developing brain of foetal irradiation.

We now live in an age worried by problems with software installation in the young. Is there a single cause for their sometimes unwelcome behaviour? Something in the water? Big Macs? EMF?

I seriously doubt the latter, but we know so little about what goes on duringinstallation that anything is possible.

homily

More than 90% of cortical neurons connect to other parts of the cortex: less than 10% connect with othe parts of the brain and the spinal cord

Pyramidalcells75%

Interneurons25%

90% intracortical connections

10% connections to other parts of the CNS

remote excitatoryconnections

local excitatorycollaterals

local inhibitoryconnections

I

II

III

IV

V

VI

WM

cell types

The adult complement of neurons isin place by birth

Peak synaptic density by 3 months

week: 0 6 12 18 24 30 36 Month: 0 6 12 18 24 30 36 Year: 4 8 12 16 20 24

EMBRYONIC POSTNATAL

Cell birth

Migration

Neurite outgrowth

Synaptogenesis

Myelination

Synapse elimination

*

*Modified from various sources inc:Andersen SL Neurosci & Biobehav Rev 2003Rakic P Nat Rev Neurosci 2002Bourgeois Acta Pediatr Suppl 422 1997 timeline

1. Pre-GD3PDGFRDM20CNP

2. OPC/O2-APDGFRDM20CNP

+ GD-3

3. Premyelinatingoligodendrocyte

DM20CNPMBPGalC

4.Myelinating oligodendrocyte

DM20 + PLPCNPMBP

Oligodendrocytedevelopment

- local embryonic origin

- migration and peakproliferationperinatally

- susceptible toperinatal stress andirradiation in childhoodand in adult

oligo 1