CS 2015

Introduction to Neuronal Networks

Christian StrickerAssociate Professor for Systems Physiology

ANUMS/JCSMR - ANU

Christian.Stricker@anu.edu.au http://stricker.jcsmr.anu.edu.au/NeuronalNetworks.pptx

THE AUSTRALIAN NATIONAL UNIVERSITY

CS 2015

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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