Quick overview of the latest finding in 2015 about the evolution and role of astrocytes and glial cells in regulating networks and particularly sleep.

1. Glial cells and astrocytes:
neural network modulators?
Hugo Trad & Stephen Larroque
2 Nov 2015

2. Glia/Neuron ratio
• Glia not just a « glue », lots of different
functions
• Friede (1954) : Glial index, or glia/neurons
(G/N) ratio
• How does this ratio vary across species, and
to what extent this variation can be
informative of glia’s function ?
2
(Herculano-Houzel, 2014)

3. G/N varies with brain size?
3
(Herculano-Houzel, 2014)

4. G/N varies with brain size?
4
(Herculano-Houzel, 2014)

5. G/N varies with brain size?
5
(Herculano-Houzel, 2014)

6. G/N varies with neuronal density
6
(Herculano-Houzel, 2014)

7. G/N varies with neuronal density
7
(Herculano-Houzel, 2014)

8. Varies with neuronal density?
• Why ?
– Metabolic argument : larger neurons because of
smaller neuronal density (= metabolic cost?)
8
(Herculano-Houzel, 2014)

9. Varies with neuronal density?
• Why ?
– Metabolic argument : larger neurons because of
smaller neuronal density (= metabolic cost?)
9
(Herculano-Houzel, 2014)

10. Varies with neuronal density?
• Why ?
– Developmental argument : glia can proliferate
during postnatal development
– Glia : small size variations
and uniformly distributed
(contrary to neurons)
→ G/N vary with neuronal
density (not glial density)
– Consistent with data !
10
(Herculano-Houzel, 2014)

11. Implications of G/N ratio
• Uniform variation → highly conservated
throughout evolution
• Suggests glial cells perform fundamental role,
since they can hardly be altered
• May favor sparse coding
• Human exception : larger and more complex
astrocytes. Why ?
– Brain size vs intrinsic properties of human astrocytes ?
– Core to human cognition ?
11
(Herculano-Houzel, 2014)

12. Why is sleep important?
• Essential for memory and cognitive functions
• Universal for all animals with a brain (mammals, birds,
insects?, etc.)
• Necessary, else death is guaranteed
• Precise physiological (REM/NREM, slow waves) or
behavioral (no response to stimuli) definitions
• Compensation after deprivation (more frequent slow waves)
• Questions :
– What functionality ?
– How it works ? 12

13. Sleep functionality: theories
• Synaptic homeostasis (SHY) (Tononi & Cirelli,
2003) : wake LTP-potentiated synapses weights
are normalized during sleep for efficiency
• Memory trace replay (Lee & Wilson,2002) :
memories are consolidated by offline
reactivation during sleep
=> Sleep = regulation of plasticity ?
=> Contradictory or complementary theories?
13

14. Local synaptic modulation
14
• 2 pathways for local synaptic modulation by astrocytes :
(2B) A1 pathway is tonically activated to clean neurotransmitters,
While phasic A1 activation can regulate depending on synaptic activity
(Fellin et al, 2014)

15. Up-down states modulation
15
• Slow waves reduction in sleep-deprived dnSNARE mice can be
explained by the modulation of up-down states probabilities :
Deprived dnSNARE mice cannot compensate !
(Fellin et al, 2009)

16. Take home message
• Astrocytes :
– Active synaptic modulators (not just passive regulators)
similar to neurons gatekeepers (synaptic gating)
– Highly conservated throughout evolution = essential role
– Essential (core?) for sleep (and thus memory) functions
• Questions :
– Characteristics intrinsic or due to neural environment ?
– Astrocytes participate in the formation of complex neural
networks ? Do evolved astrocytes allow to better learn ?
16

17. – The Glia/Neuron Ratio, Herculano-Houzel, 2014, Glia, 62(9), 1377-1391.
– Astrocyte regulation of sleep circuits: experimental and modeling
perspectives, Fellin et al, Frontiers in Computational Neuroscience, 2014
– Time to be SHY? Some comments on sleep and synaptic homeostasis,
Tononi & Cirelli, 2012, Neural plasticity.
– Astrocytes drive neural network synchrony, Levine-Small & Guebeli &
Goddard & Yang & Chuong & Chow & Egert, 2012, In MEA Meeting 2012(p.
30).
– Memory of sequential experience in the hippocampus during slow wave
sleep, Lee & Wilson, 2002, Neuron, 36(6), 1183-1194.
– Reverse replay of behavioural sequences in hippocampal place cells
during the awake state, Foster & Wilson, 2006, Nature, 440(7084), 680-
683.
References
slideshare.net/LRQ3000

18. Thank you!
slideshare.net/LRQ3000

19. Bonus Slides

20. Network synchrony modulation
23
Local phasic ATP/Adn modulation may promote global synchrony :
(Fellin et al, 2014)

21. Sleep-deprived dnSNARE mice
24
• Sleep-deprived dnSNARE mice have difficulties to compensate
when under high homeostatic sleep pressure :
Deprived dnSNARE mice have reduced compensation !
(Fellin et al, 2009)

22. Bistable neurons, synaptic gating
25
• Bistable neurons can switch between two states : Up and Down
• Allow to create selective inhibition (aka : synaptic gating)
• A third neuron (or astrocyte?) can modulate this gating : the
gatekeeper

23. Up and down state in one neuron
26
• Up-state = depolarized ; Down-state = hyperpolarized (close to
membrane potential).
• Change neuron’s dynamics ; Up needs balanced excitation and
inhibition ? (Wilson & Cowan 1972)
• Can switch state without triggering a spike
DownDownUpUp

24. Up and down states
27
• Up and down states in dnSNARE mice (in-vivo patch-clamp
recordings from pyramidal neurons in somato-sensory cortex) :
(Fellin et al, 2009)

25. Neural oscillations
28
• Oscillation = rythmic pattern of activation of a
single neuron or a network

26. THE END