1. Signal processing/integration (AP, dendrites) 3 1 2
Signal processing/integration (AP, dendrites)
Output (vesicle release, AP-release coupling)
Input (single channel, whole cell currents, chemical synapses)

2. U R = I τ = R·C Basics resistance capacitor Ion channels vs. pumps
Resistive capacitive components
Reversal- and membrane potential

3. Basics Number of neurons in the human brain: ~8.5·1010
Dudok Barna, Katona lab
Number of neurons in the human brain: ~8.5·1010
Number of synapses in the human brain :
Number of neurons in the human neocortex: ~2·1010

4. Signal processing/integration (AP, dendrites) 3 1 2
Signal processing/integration (AP, dendrites)
Output (vesicle release, AP-release coupling)
Input (single channel, whole cell currents, chemical synapses)

5. Neuronal signal processing
AD/DA converter
dendrites
axon initial
segment
axon

6. τ = R·C Analogue signal propagation RC circuit cabel-theory τ = rmcm
áram
feszültség
 τ = rmcm
τ = R·C

7. τ = R·C Analogue signal propagation RC circuit Rectifycation
(active components)
áram
feszültség
áram
feszültség
τ = R·C

8. Voltage clamp IM = Iion + Icap Icap = cm · dV dt
A. L. Hodgkin
A.F. Huxley
Nobel Prize in Physiology, 1963

9. Na+ és K+ currents during the AP
Measured ionic currents
Theoretical currents/conductance

10. Single channel patch clamp
Hamill et al., 1981
Erwin Neher, Bert Sakmann
Nobel Prize in Physiology, 1991

11. Single channel patch clamp
Hamill et al., 1981 Im

12. Ionic channels Na+ channels: fast activation, inactivation
K+ channels: delayed

13. Structural similarity: 4x6TM
S5-S6 domain: „water” pore, selectivity
S1-S4domain: votlage-dependency
gating S6 and S4-5 link

14. Voltage-dependence (non linear IV)
- S4 domain:
6-7 + charges by Arg, Lys,
conformation changes (paddle S4>S1)
Selectivity: P-loop

15. - high Na-channel densitiy - left-shifted V-dependence
Axon initial segment:
- one per cell
- high Na-channel densitiy
- left-shifted V-dependence
AP initialization
Hu et al.
Kole et al.
Lőrincz & Nusser

16. Supralinear integration
NMDA spike
Losonczy & Magee, 2006
dendritic
Na+ spikes

17. Signal processing/integration (AP, dendrites) 3 1 2
Signal processing/integration (AP, dendrites)
Output (vesicle release, AP-release coupling)
Input (single channel, whole cell currents, chemical synapses)

18. Quantal release of neurotransmitters
Bernard Katz,
Nobel Prize in Physiology, 1970

19. Synaptic vesicle release
Change in membrane capacitance = change in membrane surface

20. Synaptic vesicle release
Quantal dye „release”

22. Synaptic vesicle release
James E. Rothman, Randy W. Schekman,Tom Südhof,
Nobel Prize in Physiology, 2013

23. calcium-influx dependent
The release is
calcium-influx dependent
Calcium chelators with different kinetics
Calcium sensitive dyes

24. Signal processing/integration (AP, dendrites) 3 1 2
Signal processing/integration (AP, dendrites)
Output (vesicle release, AP-release coupling)
Input (single channel, whole cell currents, chemical synapses)

25. Paired recordings Whole cell patch clamp in vitro brain slice
posthoc anatomy
CR-GFP CR

26. Chemical synapses Receptor: ligand-, and ion-selective
postsynaptic
AMPA MP
Outward current=
hyperpolarization
presynaptic
Inward current=
depolarization
Receptor: ligand-, and ion-selective
Ionotropis – Metabotropic receptors
Konduktancia változás

27. Ligand-activated ion channels
„Indirect” metabotropic receptors

28. Specificitás
Affinitás
Agonsiták/Antagonisták/Alloszterikus modulátorok

29. Optogenetics

30. Signal processing/integration (AP, dendrites) 3 1 2
Signal processing/integration (AP, dendrites)
Output (vesicle release, AP-release coupling)
Input (single channel, whole cell currents, chemical synapses)

31. Undergrad and “TDK” positions are available for studying hippocampal connectivity and dendritic integration using patch clamp recordings of synaptically connected, anatomically identified neurons, calcium imaging and dendritic and axonal recordings.
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