1. LAMINAR DEVELOPMENT

How do V1 Ocular Dominance &Orientation maps develop?

Ocular dominance columns and orientation tuningare found before eye opening in the cat

How do cortical columns form?

Consistent tuning in vertical V1 penetrations beforeinterlaminar cortical connections have matured

HYPOTHESIS: The Cortical Subplate

Model of laminar development

Subplate develops maps that are

taught to LGN-to-layer 4 connections

Subplate input guides layer 2/3

clustering

Subplate input guides layers 4 and

2/3 connections

Grinvald (http://www. weizmann.ac.il/brain/images/cubes.html)

2. ADULT ORGANIZATION OF V1

Ocular Dominance Columns (ODCs)

Alternating stripes of cortex respond preferentially

to visual inputs of each eye

R/L in Figure

Orientation Columns

A smooth pattern of changing orientation

preference

Organized in a pinwheel like fashion

( in Figure)

Horizontal projections

connect areas of same

ocular dominance

Horizontal projections

connect areas of similar

orientation preference

3. LATERAL CONNECTIONS IN V1

Clusters of lateral projections are found in the

supragranular and infragranular layers

Bosking et al., 1997

Retina

Oriented

Learns geniculocortical map

Unoriented

On Center / Off surround

Learns corticogenicular map

Random retinal activity

drives network before eye

opening

Subplate

LGN

7. MODEL SUBPLATE MAP

Orientation Map Learned in Subplate

Left

Monocular Stripes

Afferents compete for

territory

Monocular Layers

Conserved # synapses

Eyes are uncorrelated

Subplate

LGN

Ocular Dominance Map Learned in Subplate

Retina

Right

Subplate map is taught to Layer 4

Patterned visual inputs drive segregation ofON and OFF subfields in Layer 4 neurons

At stimulus edges, ON and OFF thalamic cells arespatially out of phase and thus anti-correlated

Left Right

Retina

LGN

Subplate

Layer 4

8. MODEL LAYER 4 MAP

Oriented

Learned Layer 4 map

emulates LGN-Subplatemap

Subplate activity guides

development of LGN to

Layer 4 connections

ON and OFF layersbecome equally active

when eyes open

When eyes open,

random retinal activity

is replaced by patterned

visual inputs

9. MODEL LAYER 2/3 MAP

Subplate guides horizontal connections

Retina

LGN

Subplate

Left Right

Layer 2/3

Synapses with Subplate

in Layer 1

Clustered horizontal

connections

Layer 4 develops

connections to 2/3

Subplate activity

instructs developmentof Layer 2/3 connections

On Center / Off surround

Random retinal activity

drives network before

eye opening

Layer 4

10. MODEL LGN-TO-SUBPLATE MAP

Orientation Columns

Ocular Dominance Columns

Ocular Dominance Columns

develop in subplate with

help of conservation of LGN

synapses

[plot of ocularity index]

Oriented cells self organize

in subplate

[Length shows degree of

orientation tuning and angle

shows prefered orientation]

11. QUANTIFICATION OF SUBPLATE

TUNING

Matrices of Weights

Feedforward pattern of

connections from the LGN

Receptive fields initialized as

weight noise

Oriented profiles develop

Peak Orientation

Network is probed with

stimuli of different orientation

Peak orientation is plotted

Length shows orientation

index

Orientation Tuning Curves

Orientation tuning curves

calculated for each cell

Most fit gaussian profile withhalfwidths ~30˚ for tuned cells

0.79 1.00

0.54 0.48

12. LEARNED LGN-TO-4 MAP

Subplate Layer 4

Ocular Dominance Columns

Orientation Columns

Maps in the Subplate are taught to Layer 4

13. RECIPROCAL CONNECTIONS

BETWEEN LGN & SUBPLATE

Oriented corticofugal connections match

orientation of V1 cells

LGN to Subplate

Subplate to LGN

Orientation same as LGN to

Subplate connections

Patterns are transferred to

the later developing layer 6

to LGN connections

Raw connection patterns

Data from monocular OFF

simulation

Weights are clearly oriented

Murphy et al., (1999)

Model Results

AFFERENTS FROM ON LAYERS

AFFERENTS FROM OFF LAYERS

14. ON/OFF IN LAYER 4

ON and OFF segregation when eyes open

Spatially offset ON & OFF cells fire to same edge

Anti-correlation drives segregated receptive fields

Significant diversity exists in arrangement of ON

and OFF subfields in cortical receptive fields

15. MODEL SUBPLATE ABLATION

Ocular Dominance Columns fail to develop

Orientation Tuning fails to develop

Some cells have a significant

tuning index but inspection of

the curves show no tuning

(Ghosh & Shatz 1992)

(Kanold et al., 2001)

16. LAYER 2/3 CLUSTERED

HORIZONTAL CONNECTIONS

Subplate Guides Horizontal Clusters

Reciprocal connections between layer 2/3 cells

Cluster precision due to local isotropic filters

Size and spacing due to size of filters

Noisy filters would result in more realistic pattern

Model Results

17. LAYER 4-TO-2/3 CONNECTIONS

Subplate Provides Vertical Correlations

Focused connections contrast with 2/3 clusters

Learning gated by layer 2/3 activity

Connections develop without use of distance bias

Model Results

18. BDNF AND SUBPLATE ABLATION

Subplate ablation increases cortical BDNF

Increase or Decrease of BDNF blocks ODC

BDNF affects release of Glutamate and GABA

Model insights: Parameters Matter

Increasing excitation reduces the selectivity of

cells by enlarging their receptive fields

Increasing inhibition reduces activity and

results in noisier receptive fields

Equally changing both excitation and inhibition

causes a shift in balance

Increasing total input can reduce network

activity since DOGs suppress uniform inputs

(Ghosh & Shatz, 1994)

(Cabelli et al., 1995, 1997)

(Berardi & Maffei, 1999)

19 OTHER MODELS

Most models are single layered

Other developmental models have not

demonstrated how vertical columns arise

Clustering in Layer 2/3 rarely addressed

The coordinated development of layer 2/3 horizontal

connections with maps of orientation and ocular

dominance has not previously been modeled

The subplate goes unnoticed

Our model is the first to use the subplate to explain

cortical development

LAMINART Model (Grossberg and Williamson 2001)

Demonstrates how patterned vision can refine

horizontal connections in Layer 2/3

After development these circuits generate

properties of adult perceptual grouping

The present model is consistent with these results

20. CONCLUSIONS

Subplate enables development of Columns

Learns Orientation and Ocular Dominance Maps

Teaches OR and ODC to Layer 4

Instructs clustering of Layer 2/3 connections

Guides growth of interlaminer connections

Removal of Subplate eliminates map formation

Eye opening segregates ON & OFF inputs

The introduction of patterned vision provides a

spatial anticorrelation of ON and OFF cells

Future Directions

Allow subplate to die

Develop layer 2/3 maps

Incorporate more realistic inhibitory circuit and

develop inhibitory connections

Generalizes model to other cortical areas, such as

A1 and extrastriate areas

21. REFERENCES

Albus, K., & Wolf, W. (1984). J Physiol , 348, 153-185.

Allendoerfer , K. L., & Shatz , C. J. (1994). Annu Rev Neurosci , 17,

185-218.

Bosking , W. H., Zhang, Y., Schofield, B., & Fitzpatrick, D. (1997).

J Neurosci , 17(6), 2112-2127.

Cook, P. M., Prusky , G., & Ramoa , A. S. (1999). Vis Neurosci ,

16(3), 491-501.

Crair, M. C., Horton, J. C., Antonini , A., & Stryker, M. P. (2001). J

Comp Neurol , 430(2), 235-249.

Ghosh , A., & Shatz , C. J. (1992).. Science, 255(5050), 1441-1443.

Ghosh , A., & Shatz , C. J. (1994). J Neurosci , 14(6), 3862-3880

Grossberg, S., & Williamson, J. R. (2001). Cereb Cortex, 11(1),

37-58.

Kanold , P.O., Kara, P., Reid, R.C., Shatz , C.J. (2001). Soc.

Neurosci . Abstr ., P27.16.

Murphy P.C., Duckett S.G., Sillito A.M.(1999). Science, 286,

1152-1154.

Yoshioka, T., Blasdel , G. G., Levitt , J. B., & Lund, J. S. (1996).

Cereb Cortex, 6(2), 297-310.

S upported in part by AF OS R , DAR P A, NS F , and ONR .

Crair et al., 2001

4. VISUAL DEVELOPMENT TIMELINE

OFF field bias

Cortical cells respond to negative contrast stimuli

76% at P8

Contralateral Bias

At P8 contralateral eye dominates

Horizontal Connections

ODCs project more to areas of same dominance thanother dominance

Iso-oriented areas project primarily to areas of similarorientation

~20-30% of projections to different “modules”

VisualCortex

Lateral

GeniculateNucleus

E37 E44 E51 E58 E65/P0 P7 P14 P21 P28

LGN axons

in Subplate

LGN axons in

cortical plate

(layers 5 and 6) LGN axons

in Layer 4

Ocular

dominance

columns

emerge

Orientation

selective

neurons

detectedCritical period

for visual

deprivation

Retinal ganglion

cell afferents in

LGN Retinogeniculate

afferents

segregate

LGN

cytoarchitechtonic

lamina differentiate

Albus & Wolf 1984

Crair et al., 2001

Molecular gradients provide a crude map

Epherins, Netrins, Semaphorins, Slit, etc.

Activity refines existing maps

Activity provides correlations between related cells

Retina TectumNasal Temporal Anterior Posterior

A Nasal-Temporal

gradient of Eph receptors

in retinal ganglion cells

interact with anterior to

posterior gradients of

repellant epherin ligand

in the Tectum. The result

is a crude retinotopic

map.

Normal Development ‡

Binocular Deprivation ‡

Monocular Deprivation ‡

Cook et al., 1999

LGN

5. DEVELOPMENTAL MECHANISMS

TTX

6. CORTICAL SUBPLATE

Cortical subplate forms circuit with LGN

LGN afferents wait in subplate for weeks before they

synapse in cortical plate (Ghosh & Shatz 1994)

Ablation of subplate stops map formation

When subplate is ablated, ocular dominance

columns fail to form (Ghosh & Shatz 1992)

Orientation tuning and orientation maps do not

develop after subplate ablation (Kanold et al., 2001)

Subplate connects to Layer 4 (Ghosh 1995)

Connections exist from subplate to Layer 4 when

LGN afferents begin to grow into Layer 4

Subplate connects to Layer 2/3

Subplate connects to Layer 1 (Allendoerfer & Shatz 1994)

Layer 2/3 has dendritic arborizations in Layer 1

Migrating Neuron

How Do Laminar Circuits Develop? The Role of the Cortical Subplate in the Development

and Laminar Coordination of Orientation and Ocular Dominance Maps in V1Aaron Seitz and Stephen Grossberg

Department of Cognitive and Neural Systems, Boston University, Boston, MA

aseitz@bu.edu steve@bu.edu http://www.cns.bu.edu/~aseitz