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
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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
length constantmembrane resistance
internal resistance
• thin dendrites have short length constants (large ri)
• leaky dendrites have short length constants (small rm)
The length constant is the distance at which 37% of Vmax has been reached during the fall of voltage
Length constant is proportional to square root of process diameter
Dendrites – electrotonic features
• Synaptic potentials passively conducted down a dendrite are
• attenuated• slowed• temporally filtered
Slowing and attenuation of distal inputs
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
Spatial SummationTemporal Summation
A potential problem:dendritic filtering
Because of the leaky cable structure of dendrites, inputs fade away with distance.
Can distal inputs influence spiking?
Mitral cells of olfactory bulbdriven effectively by distal input
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.
Spines – electrotonic featuresIncrease length constant
Increase input resistance Decrease internal resistance
Ri large Ri small
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.
Spines – electrotonic featuresIncrease strength of distal synapses
Magee and Cook, 2000
Synaptic strength is higher for distal synapsesso soma “sees” similar EPSP amplitudes
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?
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
Dendrites can generate spikes
Llinás and Sugimori 1980
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
Hausser et al., Science 290, 2000
stimulate soma stimulate dendrite
pyramidal cell
Purkinje cell
Retinal bipolar cells• electrotonically compact
• few active conductances in dendrite or axon
• lack regenerative spikes
• yet effectively communicate synaptic inputs to inner retina
Grimes et al., Neuron 65, 873, 2010
Dendritic compartments can act independently
A17 amacrine cells
• single vericosities operate independently• efficiency of single shared soma
Horizontal cells: uncoupled dendritic and axonal compartments
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•
Dendritic spikes propagate in both directions
Forward Propagation Backpropagation
Early evidence for somadendritic spikes
Eccles, 1957
Hausser et al., Science 290, 2000
Contemporary evidence for dendritic spikes
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
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
•
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
Spines – role in plasticity
• Big changes in spine form and motility in development
• Enriched environments increase spine number
• LTP more and bigger spines •
Abnormal spine morphology in a model of mental retardation
wildtype Fragile-X
www.neurostructural.org/images/nine.jpg
normal Alzheimer’s
Spine loss in neurodegenerative diseases
Dendrites as presynaptic elements
excit
inhib
sum
Mitral cell dendrodendritic synapsesself and lateral inhibition
Lin and Koleske, 2010
Bhatt et al., 2009
Bhatt et al., 2009
Most retinal amacrine cells lack axons
Gap junction - substrate for electrical synapses
Wagner, C. Kidney International (2008) 73, 547–555
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
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
Grimes et al., Neuron 65, 873, 2010
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
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
Direction of Dendritic Spikes is Bidirectional
Forward Propagation Backpropagation
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.
Hausser et al., Science 290, 2000
Hausser et al., Science 290, 2000
