1 / 24

THE AUSTRALIAN NATIONAL UNIVERSITY

THE AUSTRALIAN NATIONAL UNIVERSITY. Introduction to Neuronal Networks Christian Stricker Associate Professor for Systems Physiology ANUMS/JCSMR - ANU Christian.Stricker@anu.edu.au http:/ /stricker.jcsmr.anu.edu.au/NeuronalNetworks.pptx. Aims.

truda
Download Presentation

THE AUSTRALIAN NATIONAL UNIVERSITY

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. THE AUSTRALIAN NATIONAL UNIVERSITY Introduction to Neuronal NetworksChristian StrickerAssociate Professor for Systems PhysiologyANUMS/JCSMR - ANUChristian.Stricker@anu.edu.auhttp://stricker.jcsmr.anu.edu.au/NeuronalNetworks.pptx

  2. Aims At 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.

  3. 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

  4. 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

  5. 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. • A local depolarising (inward) current serves as sink to which currents from sources flow → negative polarisation in EEG. • A local hyperpolarising (outward) current represents the source from which these will find sinks → positive polarisation in EEG. • 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.

  6. Spatial Aspects of EEG • The underlying current flow is the determinant of the polarisation: • EPSP causes a current sink at the location of the synapses: • 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 the location of synapses: • 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 3rdpower…

  7. 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.

  8. 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 not detectable on EEG. • EEG ‘spikes’ (~50 ms) correspond to highly synchronized synaptic activity and therefore follow volleys of APs.

  9. 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).

  10. Evidence for Microcircuit Concept

  11. 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 recurrents (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 column Modified from Dimitrijevicet al. (1998), Ann. N.Y. Acad. Sci. 860:360-376

  12. The Cortical Microcircuit: Inhibition • As many as >36 types of interneurons – some shown • Specific in type, location and targets. • Some types electrically coupled (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. Modified from Grillneret al. (2005), TIPS 28:525-533

  13. 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 (recept. field) • Learning in network Szentágothai (1975), Brain Res 95: 475-496

  14. Functional Consequences of Excitation & Inhibition Topologies: convergence, lateral inhibition. How small networks can produce rhythms. Spinal central pattern generators

  15. 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 at 1st neuron; convergence at 2ndneuron. • Pro: Improve transmission of small signals requiring integration of several afferents. • Con: Loss of precision in localizing source.

  16. 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).

  17. Networks and Oscillations Yuste et al. (2005), Nat. Rev. Neurosci. 6:477-483 • 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).

  18. 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

  19. 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 innerva-tion: agonists / antagonist. • A severed spinal cord can produce movement: seg-mental networks ± intact; command signals↓ from higher control centres. • Proof of concept for CPG. • Location of cells/networks currently unknown (peri-aqueductalcells?) Modified from Dimitrijevicet al. (1998), Ann. N.Y. Acad. Sci. 860:360-376

  20. 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 tetraplegicpatients.

  21. MCQ Which of the following statements best describes the inability to provide excitation within a simple network (no presynaptic inhibition observed)? • Metabolic alkalosis • Na+ channel block • K+ channel activation • Hypochloraemia • AMPA receptor desensitisation

  22. That’s it folks…

  23. MCQ Which of the following statements best describes the inability to provide excitation within a simple network (no presynaptic inhibition observed)? • Metabolic alkalosis • Na+ channel block • K+ channel activation • Hypochloraemia • AMPA receptor desensitisation

More Related