19th September 2013 Bio 334 - Neurobiology I - Target selection - map formation 1
Target selection – map formation
Raghav RajanBio 334 – Neurobiology I
September 19th 2013
19th September 2013 Bio 334 - Neurobiology I - Target selection - map formation 2
Assignment on disorders
● 1 page write-up – in layman language● Description of disorder● Present understanding of the cause?● What does this tell us about the brain?● Caveats
● Descriptions are good● Language not lay enough● Interpretation, caveats, etc. - largely missing
19th September 2013 Bio 334 - Neurobiology I - Target selection - map formation 3
Example - Synesthesia
● Our sense organs provide us with information about the world around us. Each sense provides us with a different picture of the world. Normally the senses don't overlap
● Just like sensory modalities, we also have categories for concepts like numbers, letters, etc. These are also represented in distinct regions of the brain
● Sometimes, a stimulus that normally only activates one sensory modality (or a particular category) involuntarily activates another sensory modality (or category)
● eg: a particular number or letter is also associated with a particular colour
19th September 2013 Bio 334 - Neurobiology I - Target selection - map formation 4
Quote from a person with number colour synesthesia
"A few years ago, I mentioned to a friend that I remembered phone numbers by their colour. He said "So you're a synesthete!" I hadn't heard of synesthesia (which means something close to 'sense-fusion') – I only knew that numbers seemed naturally to have colours: five is blue, two is green, three is red… And music has colours too: the key of C# minor is a sharp, tangy yellow, F major is a warm brown..."[10]
19th September 2013 Bio 334 - Neurobiology I - Target selection - map formation 5
Causes of number colour synesthesia
● Not clear
● Seems to be present from childhood in most cases
● Few cases where it seems to have come about through association – for example through refrigerator magnets
● But most cases, it is present without any learning
● Maybe because of extra connections between the colour and number area
● Some evidence that it runs in families
● Can also be induced by drugs, stroke, etc.
19th September 2013 Bio 334 - Neurobiology I - Target selection - map formation 6
Interpretation, future research ...
● Some commonalities of synesthetic experience suggests that even abstract concepts like numbers may be represented in the same place and same way across individuals
● Suggests that wiring in the young brain may be more widespread and non-specific
● Pruning of extra connections may happen as the brain matures
● Although since it occurs after drugs, it might even be just a case of the balance between excitation and inhibition
● Two aspects of connectivity – anatomical vs. functional● More studies on specificity of responses of a particular
brain region to one sensory modality
19th September 2013 Bio 334 - Neurobiology I - Target selection - map formation 7
Connecting up with the right cells – networking!
● End result – very well organized maps
Dan H Sanes, Thomas A Reh, William A Harris. Development of the Nervous System 2005 – Chapter 6
19th September 2013 Bio 334 - Neurobiology I - Target selection - map formation 8
Neurotrophins and their receptors can help axons choose the right targets
● Typically neurotrophins expressed by the target region
● Receptors expressed by the navigating axons
● Considerable number of different neurotrophins
● Nobel prize – Rita Levi Montalcini, Stanley Cohen (1986)
Dan H Sanes, Thomas A Reh, William A Harris. Development of the Nervous System 2005 – Chapter 6
19th September 2013 Bio 334 - Neurobiology I - Target selection - map formation 9
Dendritic target selection based on neurotrophic cues in the inner ear
● Dendrites of all cells express receptors for both NT-3 and BDNF
● Early growth is independent of neurotrophic cues
● BDNF can replace NT-3 with some excess innervation
● Neurotrophins also promote growth and survival
Dan H Sanes, Thomas A Reh, William A Harris. Development of the Nervous System 2005 – Chapter 6
19th September 2013 Bio 334 - Neurobiology I - Target selection - map formation 10
In the absence of their normal targets, axons will innervate neighbouring targets ...
● LGN degenerates after ablation of visual cortex
● Superior colliculus lesioned
Dan H Sanes, Thomas A Reh, William A Harris. Development of the Nervous System 2005 – Chapter 6
19th September 2013 Bio 334 - Neurobiology I - Target selection - map formation 11
... except, as always, border patrols try to control infiltration
● Presence of normal axons
● Presence of molecular cues
● All these prevent infiltration
● They also serve to keep axons inside the target area
Dan H Sanes, Thomas A Reh, William A Harris. Development of the Nervous System 2005 – Chapter 6
19th September 2013 Bio 334 - Neurobiology I - Target selection - map formation 12
Such erroneous connections can retune cortical areas to reflect properties of the input
● Orientation selective columns appear in rewired ferret A1
● Some differences with such columns in V1
http://web.mit.edu/msur/www/publications/induction.pdf
19th September 2013 Bio 334 - Neurobiology I - Target selection - map formation 13
Can rewired auditory cortex see the light?
● Animals trained to get reward on the left for a sound stimulus● Reward on the right for a visual stimulus● Trained with visual stimuli only in the left visual field● Tested wit h visual stimuli in the right visual field
http://web.mit.edu/msur/www/publications/visual.pdf
19th September 2013 Bio 334 - Neurobiology I - Target selection - map formation 14
More about the methods
● After training, they were tested with light on the right visual field
● They can respond with left V1 or left A1
● So next, left V1 was ablated
● And finally, left A1 was also ablated
http://web.mit.edu/msur/www/publications/visual.pdf
19th September 2013 Bio 334 - Neurobiology I - Target selection - map formation 15
Auditory cortex sees (NOT HEARS) the light
http://web.mit.edu/msur/www/publications/visual.pdf
19th September 2013 Bio 334 - Neurobiology I - Target selection - map formation 16
After reaching the target area, very nice topographical maps form
● Visual system topography organized by location in space
● Olfactory system topography organized by receptor type expression
Dan H Sanes, Thomas A Reh, William A Harris. Development of the Nervous System 2005 – Chapter 6
19th September 2013 Bio 334 - Neurobiology I - Target selection - map formation 17
Again molecular cues – could be intrinsic to the cell or area that it projects to (or both)
● Rotating the retina does not change the projection topography
● But changes behavior
Dan H Sanes, Thomas A Reh, William A Harris. Development of the Nervous System 2005 – Chapter 6
19th September 2013 Bio 334 - Neurobiology I - Target selection - map formation 18
And also experience can change wiring
● Extra whisker at birth results in extra column in S1
● Missing whisker results in missing column
● Tying two whiskers together results in merged columns
Dan H Sanes, Thomas A Reh, William A Harris. Development of the Nervous System 2005 – Chapter 6
19th September 2013 Bio 334 - Neurobiology I - Target selection - map formation 19
Summary
● A number of molecular cues help axons/dendrites reach the correct targets
● They also help keep them in the target area after they have reached
● Also correct innervation appears to compete and prevent incorrect innervation
● Caveat – incorrect innervation need not be detrimental, but in fact can still sustain correct behavior
● Activity and plasticity influence wiring to a great extent