Glial cells and astrocytes:neural network modulators?

Hugo Trad & Stephen Larroque

2 Nov 2015

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 ?

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(Herculano-Houzel, 2014)

G/N varies with brain size?

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(Herculano-Houzel, 2014)

G/N varies with brain size?

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(Herculano-Houzel, 2014)

G/N varies with brain size?

5

(Herculano-Houzel, 2014)

G/N varies with neuronal density

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(Herculano-Houzel, 2014)

G/N varies with neuronal density

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(Herculano-Houzel, 2014)

Varies with neuronal density?

• Why ?– Metabolic argument : larger neurons because of

smaller neuronal density (= metabolic cost?)

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(Herculano-Houzel, 2014)

Varies with neuronal density?

• Why ?– Metabolic argument : larger neurons because of

smaller neuronal density (= metabolic cost?)

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(Herculano-Houzel, 2014)

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 neuronaldensity (not glial density)

– Consistent with data !

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(Herculano-Houzel, 2014)

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 ?

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(Herculano-Houzel, 2014)

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

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?

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Local synaptic modulation

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• 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)

Up-down states modulation

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• 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)

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 ?

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– 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

Thank you! slideshare.net/LRQ3000

Bonus Slides

Network synchrony modulation

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Local phasic ATP/Adn modulation may promote global synchrony :

(Fellin et al, 2014)

Sleep-deprived dnSNARE mice

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• Sleep-deprived dnSNARE mice have difficulties to compensate when under high homeostatic sleep pressure :

Deprived dnSNARE mice have reduced compensation !

(Fellin et al, 2009)

Bistable neurons, synaptic gating

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• 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

Up and down state in one neuron

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• 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

Up and down states

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• Up and down states in dnSNARE mice (in-vivo patch-clamp recordings from pyramidal neurons in somato-sensory cortex) :

(Fellin et al, 2009)

Neural oscillations

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• Oscillation = rythmic pattern of activation of a single neuron or a network

THE END