Neuronal Anatomy and Electrical Activity

Transcription

1 Neuronal Anatomy and Electrical Activity Mark S. Cohen UCLA Psychiatry, Neurology, Radiology, Psychology, Biomedical Physics

2 Topics anatomy of single neurons resting and action potentials transmission of signals chemical and electrical synapses information coding BOLD and unit activity EEG & SITE MR-visible effects

3 Types of Neurons Dendrites Soma (cell body) Axon terminals Axon

4 Resting Potential Typical: -9 < resting potential < -6 mv

5 Development of the Membrane Potential

6 Development of the Membrane Potential

7 Development of the Membrane Potential E = RT F ln [C ] inside [C outside ] Nernst Potential: 27mV ln [C inside ] [C outside ]

8 Observed Ion Concentrations [Na] 46 mm [K] 1 mm E = RT [Na] 5 mm [Cl-] 54 mmp [A] [Cl-] p [B] 4-1 p A mm [x] p in B in -45[y] x out y to -7 out mv A,B are [A-] 35 cations mm 3 Na out 2 K in Nernst C 6 mv " [K] 4 mm -95 mv F ln p A [A] out p B [B] out p y [x] in p y [y] in $ # x,y are anions % ' & 75 mv

9 Structure of the Cell Membrane Extracellular Fluid Glycoprotein 5 nm Polar Head Cholesterol Carbohydrate Integral Protein Peripheral Protein Cytoskeletal Filament Cytoplasm Nonpolar Tail Note: E-field is >1 MV/m! Taken from Human Biology by Daniel Chiras

10 Electrical Behavior of Neurons i V Axon Ringer s Sol n i 5 mv in out Action Potential -5-1

11 Current and Voltage 1 Sodium Permeability Transient conductance increase mv 5 Potassium Permeability Voltage-dependent conductance -5 Neurons are REFRACTORY after each Action Potential Membrane Potential -1 1 ms After Hodgkin and Huxley, 1952

12 Sodium Leakage with Action Potentials Cell Volume = 9 x 1-13 liters, about half of which is liquid. At 4 mm Sodium: = 4. x 1-14 Moles Sodium/cell Na With Each Action Potential: ΔV =.13 Volt Q = CV = 1.3 x 1-7 Coulombs /cm 2 = 1.4 x 1-12 Moles/cm 2 Surface Area = 2.8 x 1-5 cm 2 Each AP passes 3.7 x 1-17 Moles of Na 1 µm C = 1µF/cm 2 [Na] is increased by.1% with each Action Potential!

13 Sodium Potassium Pump After Matthews and van Holde: Biochemistry 2/e Initial State Pump Open to Inside β β Potassium Expelled to Inside α α β β Na Taken from Inside β K α K α Na Na α Na K K Na β α Na Na Dephosphorylation Stimulates Conformation Change P ATP Phosphorylates α Subunit and Stimulates Conformation Change ATP INSIDE OF CELL ADP β K Two Potassium Ions Accepted from Outside K P α K α P K α α Na β Na Na P β Na β Na α α Na Sodium is Released β β Pump Open to Outside Cohen 21 Mark Cohen, all rights reserved

14 Cable Properties Extracellular r m C m r m C m r m C m r m C m E m Intracellular r i x r i r i r i V x /V o V x V = e x λ λ = r m /r i 2λ λ λ 2λ x For vertebrate neurons: µm < λ < mm

15 Cable Properties Extracellular r m C m r m C m r m C m r m C m E m Intracellular r i x r i r i r i V For vertebrate neurons:.5 msec < τ < 5 msec msec

16 Propagation of the Action Potential V 1 V 2 V 3 V 4 V 1 V 3 V 2 V 4 Resulting Velocity ~1-3m/sec

17 Propagation of the Action Potential V 1 V 2 V 3 V 4 V 1 V 3 V 2 V 4 Resulting Velocity ~1-3m/sec

18 Propagation of the Action Potential V 1 V 2 V 3 V 4 V 1 V 3 V 2 V 4 Resulting Velocity ~1-3m/sec

19 Propagation of the Action Potential V 1 V 2 V 3 V 4 V 1 V 3 V 2 V 4 Resulting Velocity ~1-3m/sec

20 Propagation of the Action Potential V 1 V 2 V 3 V 4 V 1 V 3 V 2 V 4 Resulting Velocity ~1-3m/sec

21 Propagation of the Action Potential V 1 V 2 V 3 V 4 V 1 V 3 V 2 V 4 Resulting Velocity ~1-3m/sec

22 Propagation of the Action Potential V 1 V 2 V 3 V 4 V 1 V 3 V 2 V 4 Resulting Velocity ~1-3m/sec

23 Propagation of the Action Potential V 1 V 2 V 3 V 4 V 1 V 3 V 2 V 4 Resulting Velocity ~1-3m/sec

24 Propagation of the Action Potential V 1 V 2 V 3 V 4 V 1 V 3 V 2 V 4 Resulting Velocity ~1-3m/sec

25 Myelin Sheath 1 Å

26 Nodes of Ranvier

27 Saltatory Conduction Internode: High Membrane Resistance Long Spatial Constant Short Time Constant Efficient Electrotonic Conduction Myelin Axon Node: Low Membrane Resistance High Membrane Current Flow Fires Action Potential Action Potential Regeneration

28 White and Gray Matter Trans-Calossal Fibers Optic Radiations Arcuate Fibers After: Catani, et al., NeuroImage 17:77, 22

29 EPSP s: Excitatory Post-Synaptic Potentials Muscle end plate potentials Recorded in low Ca 2 / high Mg 2 Boyd & Martin, # of Observations Amplitudes are quantized and display a Poisson distribution Measured Potential (mv)

30 Reversal Potential Outward 2 na 38 mv V set epsp s result from increased K and Na conductance, with ΔNa > ΔK 2 Inward -15 mv Neuron Extra-cellular fluid -12 mv i out msec After Magleby and Stevens, 1972

31 Neural Synapse Microtubules Synaptic vesicles Synaptic Bouton Synaptic Cleft Synaptic Cleft Golgi Complex Synaptic vesicles Mitochondrion Dendritic Spine Presynaptic Membrane Postsynaptic Membrane From:

32 Synapses by EM Flat Vesicles Round Vesicles Mitochondria Synaptic Density 2 nm Atlas of Ultrastructural Neurocytology

33 Synaptic Mechanism (movie) Delay from Presynaptic Action Potential to Post-synaptic Voltage Change is.5 msec

34 Synaptic Vesicles Exocytosis of Transmitter requires Ca 2 From: Matthews, G. Neurobiology: Molecules, Cells and Systems 2nd edn

35 Neurotransmitters Small Molecules: Acetylcholine Serotonin Histamine Epinephrine Norepinephrine Dopamine Adenosine ATP Nitric Oxide Amino Acids Aspartate Gamma-aminobutyric Acid Glutamate Glycine Peptides Angiotensin II Bradykinin Beta-endorphin Bombesin Calcitonin Cholecystokinin Enkephalin Dynorphin Insulin Galanin Gastrin Glucagon GRH GHRH Motilin Neurotensin Neuropeptide Y Substance P Secretin Somatostatin Vasopressin Oxytocin Prolactin Thyrotropin THRH Luteinizing Hormone Vasoactive Intestinal Peptide and many others

36 Electrical Synapses Gap Junction 5 nm 5 nm

37 Gap Junction Microstructure Gap Junction Channel Connexon Intercellular Gap NH 3 Connexon Subunit COO Gap Junctions have no synaptic delay, and may act as simple resistance or as electrical rectifiers Modified from:

38 SpatioTemporal Summation of psp s 2 mv Single epsp 8 ms Summated epsp s

39 Integration of Inputs Electrotonic properties of cells can result in spatial information zones within cells

40 Dendritic Spines 1 µm Atlas of Ultrastructural Neurocytology

41 How Do Neurons Encode Information? Action Potentials are Identical! 1. Firing Rate: Ranges up to 1 spikes/ second 2. Labeled Channels: Each neuron has different information content 3. Modification of Synaptic Efficacy 4. Firing Synchrony 5. Transmitter Identity

42 Place Encoding - Basilar Membrane V 2kHz Frequency t 2Hz

43 Inhibition K efflux ms Reversal potential of Cl is near the resting potential. Therefore, its inhibition may be silent. Cl influx

44 Pre-Synaptic Inhibition Inhibitory Synapse Excitatory Synapse

45 How does BOLD relate to neural firing? Energy Demands in Transmission Pre-synaptic: Transmitter Synthesis Exocytosis Transmitter re-uptake Post-Synaptic Maintenance of membrane potential after ion leakage Excitatory: Removal of Sodium (Na/K pump) Inhibitory:???

46 Logothetis Results LFP = 4-13 Hz MUA = 3-15 Hz Pre On Post Stim Logothetis, et al., Nature 412:152, 21

47 Logothetis results Normalized Response Normalized Response Time LFP * hrf Average BOLD BOLD Normalized Response Contrast Time LFP/MUA

48 Cortical Column Blakemore, 1977

49 3 mm Imaging voxels and Neuropil 2 mm UCLA Brain Mapping Division

50 Types of Neurons Axon

51 Presumed Origin of the EEG Skin Bone CSF

52 Many Neurons are Not Seen by EEG Skin Bone Bone CSF

53 General Limitations in EEG Localization Deeper Sources Show Weaker Signals Magnitude Depends on Dipole Orientation Magnitude Depends on Temporal Synchrony Magnitude Depends on Spatial Coherence Conductivity of Body Tissues (CSF, scalp) Blur the Scalp Potentials SITE = Simultaneous Imaging for Tomographic Electrophysiology

54 EEG at Rest Fp2-F8 F8-T4 T4-T6 T6-O2 Fp1-F7 F7-T3 T3-T5 1µV 1 sec T5-O1 Fp2-F4 F4-C4 C4-P4 P4-O2 Fp1-F3 F3-C3 C3-P3 P3-O1 EKG

55 Alpha Mapping Average Power (µv 2 ) spectral power in the alpha band predicted BOLD response (sec) time (minutes)

56 SITE of Resting Alpha R Goldman (22) NeuroReport 13(18):2487

57 EEG-fMRI Issues Scalp Potentials are Proportional to the Derivative of the Voltage, whereas fmri is Proportional to the Integral of the Firing The Action Potential, per se, Is Probably Invisible to BOLD The Rhythmic Structures in the EEG May Depend More on Synchronous Firing than on High Firing Rate The BOLD Signal is Likely Associated with the Post- Synaptic Neurons

58 MR-Lucent Neurophysiology Energetic Demands (BOLD, ASL) Transmitter Synthesis, Exocytosis, Metabolism Na/K Pump [Na] Imaging Glucose Metabolism Spectroscopy Extracellular Currents (?) Phase Disturbance Anisotropic Diffusion DTI, etc Neural Constituents (NAA) Spectroscopy

59 Thanks.