The Synaptome

Question 1

What is SYNMAP?

Answer 1

• An idea aimed at looking at individual synapses on a brain wide scale
  
  • Looks specifically at protein composition, turnover and organisation on billions of individual synapses brain-wide and lifespan-wide
  • Molecular labelling -> Synapse imaging on whole brain sections -> image analysis -> synapse catalogues -> synaptome atlases -> databases -> web resources
• SYNMAP uncovered a 3D architecture of molecularly diverse synapses within the brain
• Added new taxonomy, not just excitatory inhibitory etc but based on parameters such as protein ratios, nanoarchitecture, size, lifespan etc

Question 2

What is the synaptome?

Answer 2

The set of all synapse types and subtypes in the brain

Question 3

What is synapse architecture?

Answer 3

The spatial organisation of diverse synapses

Question 4

What novel principles have been driven synaptome science?

Answer 4

• Many genetic diseases have a synaptic signature that can be traced through observation of architectural changes
• Synapse types preferentially respond to particular patterns of activity. NEW IDEA: This synaptome architecture IS a way of encoding behavioural programmes and representations
• The brains cortical columns can be considered computational units that communicate through interlayer connectivity - This is due to molecularly DISTINCT synapse types between different layers

Question 5

Discuss the role of the environment AND aging on the synaptome, including how they studied this

Answer 5

• Studied synaptome architecture in mice from birth till old age
• Generally, synapses were lost as mice aged, however not all synapses aged the same
• Some were age resilient - usually those involved in crystaline memory like language etc, whereas episodic memory synapses decayed
• Difference in synapse lifetime was found to be due to PROTEIN MAKEUP. Some having a short protein lifetime (SPL) and some having LPL)
• Big takeaway from this is that protein turnover-rate is a method of MODULATING MEMORY on MOLECULAR level
• Possible as synapse remodelling occurs every few weeks and offers possibility for reorganisation
• Magnitude of effect of environment on this was also governed by protein lifetimes
• Studied by giving mice a nice cage. Then blinding them?

Question 6

What occurs to the synaptome during sleep deprivation

Answer 6

• Decrease in synapse diversity in the Hippocampus (PhD)
• Based on protein turnover rate

Question 7

How does experience and sensory input effect the synaptome?

Answer 7

• Modifies synaptome architecture in a highly distributed network-wide manner
• Modifies particular types and subtypes of excitatory synapses
• Shifts the populations of synapses according to their protein lifetimes / turnover