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

. Segev I J Neurophysiol 2006;95: ©2006 by American Physiological Society Wilfrid Rall Modeling electrotonic properties sim.org/GENESIS/Tutorials/cnslecs/cns2a.html

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

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 Summation Temporal 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 bulb driven 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 features Increase length constant Increase input resistanceDecrease internal resistance R i large R i 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 features Increase strength of distal synapses

Magee and Cook, 2000 Synaptic strength is higher for distal synapses so 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 somastimulate 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 wildtypeFragile-X

normalAlzheimer’s Spine loss in neurodegenerative diseases

Dendrites as presynaptic elements

excit inhib sum

Mitral cell dendrodendritic synapses self and lateral inhibition

Lin and Koleske, 2010

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: ©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: ©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 Enriched environments and training increase spine 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