1. Physiology of Dendrites Passive electrical properties Active properties of dendrites How dendrites transform their inputs Dendrites as axon-like output elements Spines Special physiological features Behavior in plasticity Changes in disease and aging

2. . Segev I J Neurophysiol 2006;95:1295-1297 ©2006 by American Physiological Society Wilfrid Rall Modeling electrotonic properties http://www.genesis- sim.org/GENESIS/Tutorials/cnslecs/cns2a.html

3. length constant membrane resistance internal resistance thin dendrites have short length constants (large r i ) leaky dendrites have short length constants (small r m ) The length constant is the distance at which 37% of V max has been reached during the fall of voltage

4. Length constant is proportional to square root of process diameter

5. Dendrites – electrotonic features Synaptic potentials passively conducted down a dendrite are attenuated slowed temporally filtered

6. Slowing and attenuation of distal inputs

7. Dendrites – electrotonic features Temporal summation of synaptic inputs nearly synchronous inputs summate (but non- linearly) inputs widely separated in time do not interact Spatial summation of synaptic inputs nearby inputs summate (but non-linearly) widely separated input interact only weakly

8. Spatial Summation Temporal Summation

9. A potential problem: dendritic filtering Because of the leaky cable structure of dendrites, inputs fade away with distance. Can distal inputs influence spiking?

10. Mitral cells of olfactory bulb driven effectively by distal input

11. Possible solutions: Passive Properties Increase length constant and lower capacitance. Increase size of EPSPs distally. Active Properties Voltage-dependent ion-channels could boost the signal along the way.

12. Spines – electrotonic features Increase length constant Increase input resistanceDecrease internal resistance R i large R i small

13. Problem: changes in morphology are not always practical: In order for the length constant to double, the diameter of the dendrite has to increase by a factor of four.

14. Spines – electrotonic features Increase strength of distal synapses

15. Magee and Cook, 2000 Synaptic strength is higher for distal synapses so soma “sees” similar EPSP amplitudes

16. Vm = -60mV  25 mV 7.5 mV 67.5 mV Vrev = 0 mV However, distal inputs can only be so big… So what is a poor dendrite to do?

17. Spines – electrotonic features Small neck, high input resistance maximizes synaptic potentials Low capacitance maximizes frequency response Impedance mismatch with dendritic trunk results in asymmetric effects spine voltage has relatively little effect on dendrite (local action) dendritic voltage significantly influences spine Use voltage gated channels to boost distal inputs

18. Dendrites can generate spikes Llinás and Sugimori 1980

19. Active properties vary within and between neurons Purkinje cells P-type calcium channels Few sodium channels Little backpropagation of spikes Cortical pyramidal cells Calcium and sodium channels Robust backpropagation of spikes Some neurons have minimal active properties

20. Hausser et al., Science 290, 2000 stimulate somastimulate dendrite pyramidal cell Purkinje cell

21. Retinal bipolar cells electrotonically compact few active conductances in dendrite or axon lack regenerative spikes yet effectively communicate synaptic inputs to inner retina

22. Grimes et al., Neuron 65, 873, 2010 Dendritic compartments can act independently A17 amacrine cells single vericosities operate independently efficiency of single shared soma

23. Horizontal cells: uncoupled dendritic and axonal compartments

24. Non-linear properties of dendrites serve diverse functions Boost synaptic responses in graded fashion Thresholding (non-linear amplification of stronger inputs) Propagate spikes in anterograde or retrograde direction

25. Dendritic spikes propagate in both directions Forward Propagation Backpropagation

26. Early evidence for somadendritic spikes Eccles, 1957

27. Hausser et al., Science 290, 2000 Contemporary evidence for dendritic spikes

28. Backpropagation – functional roles Pyramidal-cells boost somadendritic spike so it invades the dendritic tree reset membrane potential for new inputs depolarize spines gate NMDA receptors coincidence detection for Hebbian increase in synaptic strength Mitral cells and dentate granule cells trigger release from presynaptic dendrites

29. Direction of information flow in dendrites affected by many factors Extent and complexity of branching (electrotonic factors) Distribution of excitatory and inhibitory synapses Distribution of voltage gated channels Interaction among all of these factors

30. Spines – special features Narrow neck  high input resistance maximizes EPSP evoked by synaptic conductance Low capacitance maximizes frequency response Impedance mismatch where neck meets shaft spine has trouble strongly influencing parent dendrites voltage fluctuations in shaft do influence spine

31. Spines – role in plasticity Big changes in spine form and motility in development Enriched environments increase spine number LTP  more and bigger spines

32. Abnormal spine morphology in a model of mental retardation wildtypeFragile-X

33. www.neurostructural.org/images/nine.jpg normalAlzheimer’s Spine loss in neurodegenerative diseases

34. Dendrites as presynaptic elements

35. excit inhib sum

36. Mitral cell dendrodendritic synapses self and lateral inhibition

45. Lin and Koleske, 2010

46. Bhatt et al., 2009

48. Most retinal amacrine cells lack axons

49. Gap junction - substrate for electrical synapses Wagner, C. Kidney International (2008) 73, 547–555

50. A-type and B-type horizontal cells in the rabbit retina have different dye-coupling properties. O'Brien J J et al. J. Neurosci. 2006;26:11624-11636 ©2006 by Society for Neuroscience

51. Cx50 plaques occur at dendritic crossings in calbindin-labeled A-type horizontal cells. O'Brien J J et al. J. Neurosci. 2006;26:11624-11636 ©2006 by Society for Neuroscience

52. Grimes et al., Neuron 65, 873, 2010

53. Spines – electrotonic features Small neck, high input resistance maximizes synaptic potentials Low capacitance maximizes frequency response Impedance mismatch with dendritic trunk results in asymmetric effects spine voltage has relatively little effect on dendrite (local action) dendritic voltage significantly influences spine

54. Spines – role in plasticity Spine morphology changes during development @ Enriched environments and training increase spine numbers @ Long-term potentiation increases spine numbers increase spine volume in single spines monitored over time

55. Direction of Dendritic Spikes is Bidirectional Forward Propagation Backpropagation

56. Active Dendritic Properties Summary: Active conductances are present in dendrites. Not uniform expression within dendrites or between neurons. Boost subthreshold EPSPs. Generate dendritic spikes. Lead to non-linear synaptic integration. Backpropagate somatic action potentials: open NMDAR, increase dendritic Ca++ levels.

57. Hausser et al., Science 290, 2000