19th september 2013bio 334 - neurobiology i - target selection - map formation1 target selection –...

19th September 2013 Bio 334 - Neurobiology I - Target selection - map formation 1

Target selection – map formation

Raghav RajanBio 334 – Neurobiology I

September 19th 2013


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


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


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]

http://en.wikipedia.org/wiki/Grapheme-color_synesthesia#cite_note-10


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.


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


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


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)



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



In the absence of their normal targets, axons will innervate neighbouring targets ...

● LGN degenerates after ablation of visual cortex

● Superior colliculus lesioned



... 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



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


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


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



Auditory cortex sees (NOT HEARS) the light



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



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



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



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


Midsem exam

● Application oriented questions● Read the chapters listed in my lectures and read

my lectures● Some multiple choice questions● Some short essay type questions – like the

disorders assignment● Good luck!!

19th september 2013bio 334 - neurobiology i - target selection - map formation1 target selection –...

Documents

target regionreceptors

particular number

neurobiology iseptember

number colour synesthesiaa

particular brain region

sensory modalitybio

sensory modalities

particular category