cs 2015 introduction to neuronal networks christian stricker associate professor for systems...
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CS 2015
Introduction to Neuronal Networks
Christian StrickerAssociate Professor for Systems Physiology
ANUMS/JCSMR - ANU
[email protected] http://stricker.jcsmr.anu.edu.au/NeuronalNetworks.pptx
THE AUSTRALIAN NATIONAL UNIVERSITY
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AimsAt the end of this lecture students should be able to
• explain how EEG traces arise;
• recognise some cortical rhythms;
• discuss the concept of cortical column and microcircuit;
• illustrate how excitation is routed through microcircuit;
• outline how inhibition endows microcircuit with richness;
• identify how connectivity shapes processing of input signals;
• recognise how excitation and inhibition can drive network
patterns; and
• illustrate how electrical stimulation can evoke locomotor
activity in spinal patients.
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Contents
• Note of neocortical evolution
• Basis of the EEG and cortical rhythms
• Concept of cortical column and microcircuit
• Flow of excitation in microcircuit
• How inhibition is highly targeted and varied
• Simple network topologies
• Excitation & inhibition in a network response
• Oscillations and central pattern generators
• Electrical stimulation in spinal patients
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Evolution of Neocortex• During evolution, human neocortex got
increasingly larger compared to other
hominoids.
• Likely that ability of the human brain is
based on neocortical size.
• Scaling laws predict cortical size:– Input (thalamus) determines the size.
– Increase in cortical volume is matched by
that of thalamus.
• However, neocortex is largely quite uniform
despite functional specializations (V1,
auditory, motor cortex, …).
• How can neocortical networks be
monitored? EEG.
Stephens (2001), Nature 411:193-195
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Basis of Electroencephalogram• EEG useful in about 50% of newly
diagnosed epileptic patients.– Gold standard for diagnosis & therapy.
• Tracks local electric fields caused by
underlying currents.– Local depolarising (inward) current serves
as sink to which currents from sources
flow → def: negative EEG polarisation.
– Local hyperpolarising (outward) current
serves as source from which these will
find sinks → positive EEG polarisation.
– Currents are summed from activity of lots
of neurons.
– Currents mostly caused by synapses.
– AP currents require large extent of
synchronisation until visible (epilepsy):
sharp waves.
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Spatial Aspects of EEG• Underlying current flow determines polarisation:
– EPSP causes a current sink at synaptic location:• If synapses in layer IV, current is sourced from apical tufts
→ positive deflection in EEG.
• If on apical tufts → negative deflection in EEG.
– IPSP causes a current source at synaptic
location:• If synapses in layer IV, current is sunk from apical tufts →
negative deflection in EEG.
• If on apical tufts, then positive deflection in EEG.
• EEG represents the spatial summation of all
activity in time and space (population
response).
• Recordings from cortical surface: superficial
layers more influential.– voltage drops off with 3rd power…
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Basic Properties
• Electrodes placed onto defined
points on scalp:– Allows for later localisation…
• Rhythms identifiable– α: 8 – 12 Hz (relaxed; eyes closed).
– β: 13 – 25 Hz (concentration, motor
activity).
– γ: 26 – 70 Hz (perception,
consciousness).
– δ: 0.5 – 3 Hz (slow wave sleep).
– θ: 4 – 7 Hz (arousal, drowsiness).
• Power of rhythms variable in
different brain areas.
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Signs of Synchronisation in EEG
• Signs of synchronisation: high frequency spikes and spike
and wave features.
• Action potentials (cellular ‘spikes’ ~1 ms) are too brief to
summate effectively and are usually undetectable in EEG.
• EEG ‘spikes’ (~50 ms) correspond to highly synchronized
synaptic activity and therefore follow volleys of APs.
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The Conundrum
• Mammalian neocortex has 6 layers.
• Cellular composition ± uniform (modular):– Few excitatory cell types
– Lots of inhibitory cell types
• Santiago Ramón y Cajal (1852-1934): – Nobel price in 1906
– Cortical microcircuit is an “impenetrable
jungle”.
• How does a uniformly structured
neocortex process sensory, cognitive and
motor information?– “Multipotent” processing modules:
microcircuit (µC).
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Evidence for Microcircuit Concept
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The Cortical Microcircuit: Excitation• “Recurrent amplifier”
• Few excitatory cell types:– Pyramidal cells (PC) and
– Spiny stellate cells (SSC).
• Input into cortex largely from– thalamus → L4 (SSC, PC)
– long-range L1 (PC)
– local recurrent axons (SSC, PC)
• Intracortical relay– from L4 → L2/3 (SSC/PC → PC)
– massive recurrents (PC → PC)
– L2/3 → L5 (PC → PC)
– L5 → L6 (PC → PC)
• Output from cortex– from L5 (PC) to BG, SC
– from L6 (PC) to thalamus
– locally to next columnModified from Dimitrijevic et al. (1998), Ann. N.Y. Acad. Sci. 860:360-376
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The Cortical Microcircuit: Inhibition
Modified from Grillner et al. (2005), TIPS 28:525-533
• As many as >36 types of
interneurons – some shown– Specific in type, location and
targets.
– Some types electrically
coupled via gap junctions.
– Characterised by peptidergic
co-transmitters.• BC: perisomatic inhibition
• BP: basal dendrites in L2-4
• MC: inhibit apical tufts
• CRC: inhibit apical tufts, in L1
• NGC: horizontal dendrites
• DBC: dendritic inhibition
• CHC: inhibition at initial segment
• Interneurons endow MC with
functional richness.
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Unresolved Questions• What constitutes a microcircuit (µC)?
– How big is it?
• Is a µC congruent with a cortical
column? – Vertically oriented “module”
– Smallest unit processing a single
sensory modality (functional def.)
– Might have a morphological correlate
(blobs, barrels, etc.)
– Cortical column made up of a single
or several µC?
• What is processed in a µC?– Feature extraction (receptive field)
– Learning in network
Szentágothai (1975), Brain Res 95: 475-496
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Functional Consequences of
Excitation & Inhibition
Topologies: convergence, lateral inhibition.
How small networks can produce rhythms.
Spinal central pattern generators
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Simple Networks
• Most important in sensory afferent processing (hearing, vision,
proprioception).
• An excitatory PC receives ~ 10’000 synapses; number of release
sites per axon is variable.
• Divergence from 1st neuron; convergence at 2nd neuron.– Pro: Improve transmission of small signals requiring integration of
several afferents.
– Con: Loss of precision in localizing source.
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Networks and Lateral Inhibition
• Without inhibition, at each level, the frequency of discharge broadens
over the whole network: summation (pro) and “smearing-out” (con).
• “Fixed” with lateral inhibition, where at each level, sharpening of
discharge strength to the centre occurs (strength of inhibition):
emergence of centre-surround inhibition (receptive fields).
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Networks and Oscillations
• Scheme works to generate – pacemakers (~SA-node): self-autonomous (CPG, next);
– excitation and inhibition (feed-back and -forward);
– inhibition typically strategically located (perisomatic); and
– requires AP adaptation: slowing of rate (self-limiting).
Yus
te e
t al.
(200
5), N
at. R
ev. N
euro
sci. 6:
477-
483
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Examples of CPGs• At all levels of motor control (oscillators)
– Spinal cord (whole program of transcription factors)• Locomotion generator
– Brainstem (& high spinal cord) - incomplete• Breathing: phrenic activity
• Swallowing
• Chewing
• Eye movements (saccades)
– Basal ganglia (see Parkinson’s disease)
– Cortex (fine control of movement)
• Feature:– Quite autonomous
– Typically require supraspinal/-brainstem command input
– Modulation by cellular properties
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Spinal Central Pattern Generator
• Paraplegic patient
• Stimuli of ~5 V intensity
(0.2 - 0.5 ms width at 25 - 60 Hz)
elicit knee movements (K.M.);
alternating innervation: agonists /
antagonist.
• A severed spinal cord can produce
movement: segmental networks ±
intact; but command signals↓ from
higher control centres.
• Proof of concept for CPG.
• Location of cells/networks currently
unknown (peri-aqueductal cells?)Modified from Dimitrijevic et al. (1998), Ann. N.Y. Acad. Sci. 860:360-376
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Take-Home Messages• EEG reflects current sources and sinks in three dimensions.
• Several different rhythms can be identified in an EEG.
• Cortical function likely related to processing in microcircuits.
• Excitation is entering L4, relayed to L2/3, then L5 which
projects outside the cortex.
• A feedback loop from L6 projects to the thalamus
(corticothalamic rhythms).
• There is a large variety of inhibition within the microcircuit.
• Oscillators emerge from interaction between excitatory and
inhibitory transmission; details given by neuronal properties.
• Locomotion is partly result of CGP activity.
• Direct spinal stimulation can initiate locomotor activity in
paraplegic patients.
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MCQ
Which of the following statements best describes the
inability to provide excitation within a simple network
(no presynaptic inhibition observed)?
A. Metabolic alkalosis
B. Na+ channel block
C. K+ channel activation
D. Hypochloraemia
E. AMPA receptor desensitisation
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That’s it folks…
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MCQ
Which of the following statements best describes the
inability to provide excitation within a simple network
(no presynaptic inhibition observed)?
A. Metabolic alkalosis
B. Na+ channel block
C. K+ channel activation
D. Hypochloraemia
E. AMPA receptor desensitisation