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Pyramidal neurons: dendritic structure and synaptic integration

Key Points

  • Pyramidal neurons have basal and apical dendrites, including an apical tuft. This preserved core structure suggests that they have conserved core functions, whereas structural variation in other areas suggests additional functional specialization.

  • A number of new methods for studying pyramidal-cell activation and circuitry are available. These include in vivo patch-clamp recording, optical activation and transgenic methods for activating, inactivating or labelling neurons and their connections.

  • Synaptic inputs from distinct sources occur onto separate dendritic domains. Defining the degree to which synapses that carry different kinds of information are segregated onto different dendritic domains remains an important challenge.

  • Most excitatory synapses onto pyramidal neurons occur on dendritic spines, but the structure of the synapses they receive differs between dendritic domains.

  • Dendritic integration of synaptic input depends on the dendritic domain that is targeted. Synapses distant from the soma tend to produce less synaptic depolarization, but this might be countered by increasing the conductance of distal synapses or by activating voltage-gated channels in dendrites. Synapses on small-diameter dendrites cause larger local voltage changes, which reduce the effectiveness of synaptic scaling but increase the activation of voltage-gated conductances.

  • Inhibitory synapses specifically target the axon, soma or different dendritic domains. Integration of inhibitory inputs also differs across cellular domains.

  • The intrinsic firing properties of pyramidal neurons vary considerably. Along with variation in dendritic structure and channel distributions, such variability suggests that different pyramidal neurons might carry out specialized functions.

  • Pyramidal-neuron dendrites contain voltage-gated channels that can influence synaptic integration. These channels can also support backpropagating action potentials and dendritically initiated spikes. Dendritic excitability is a general property of all pyramidal neurons studied so far, but the details differ between different types of pyramidal neurons. Although there is some evidence for dendritic excitability in vivo, much more work is needed in this area.

  • Activation of a small fraction of the tens of thousands of excitatory synapses on a pyramidal neuron can probably evoke dendritic spikes, but these events do not always propagate to the soma and the axon. The coupling of dendritic spikes to axonal action-potential firing probably depends on the pattern of synaptic activation. This results in forms of coincidence detection that are determined by dendritic structure and excitability.

  • Backpropagating action potentials and dendritic spikes are important signals for the induction of synaptic plasticity. Even single dendritic spikes can result in significant long-term potentiation or long-term depression.

  • Neurotransmitters can modulate pyramidal-neuron function. At least some forms of modulation affect various dendritic domains and their synaptic inputs in different ways.

  • Domain-specific properties in excitatory and inhibitory synaptic inputs, voltage-gated channels, dendritic excitability and neuromodulation all point to a multi-compartment model of pyramidal-neuron function. Elaborating simple models of pyramidal-neuron function based on these dendritic-domain-specific properties is a central challenge for the study of cortical function.

Abstract

Pyramidal neurons are characterized by their distinct apical and basal dendritic trees and the pyramidal shape of their soma. They are found in several regions of the CNS and, although the reasons for their abundance remain unclear, functional studies — especially of CA1 hippocampal and layer V neocortical pyramidal neurons — have offered insights into the functions of their unique cellular architecture. Pyramidal neurons are not all identical, but some shared functional principles can be identified. In particular, the existence of dendritic domains with distinct synaptic inputs, excitability, modulation and plasticity appears to be a common feature that allows synapses throughout the dendritic tree to contribute to action-potential generation. These properties support a variety of coincidence-detection mechanisms, which are likely to be crucial for synaptic integration and plasticity.

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Figure 1: Pyramidal-neuron structure and domains of synaptic input.
Figure 2: Dendritic spines and synapses on pyramidal neurons.
Figure 3: Dendritic-domain-specific targeting by inhibitory synapses on pyramidal neurons.
Figure 4: Dendritic excitability of pyramidal neurons.
Figure 5: Coincidence detection by excitable dendrites in pyramidal neurons.
Figure 6: Modulation of pyramidal-neuron function by metabotropic-receptor activation or activity-dependent plasticity.

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Acknowledgements

I would like to thank the following people for helpful discussions and/or comments on the manuscript: D. Ferster, J. Hardie, M. Häusser, B. Kath, G. Maccaferri, D. Nicholson, I. Raman, S. Remy, J. Waters and C. Woolley. Supported by US National Institutes of Health grants NS-035180 and NS-046064.

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Glossary

Receptive field

The area of the sensory space in which stimulus presentation leads to a response from a particular sensory neuron. Other stimulus properties, such as the optimal orientation of a bar of light, might further define the receptive-field properties of a neuron. These properties can be described in increasingly complex terms as more is learned about the conditions that are required for a particular neuron to fire.

Single-unit recording

A method that is used to measure the activity of individual neurons in awake, behaving animals.

Glutamate uncaging

The release of free glutamate by the activation of a 'caged' (chelated) glutamate compound using light.

Postsynaptic density

(PSD). An electron-dense thickening underneath the postsynaptic membrane at excitatory synapses. PSDs contain receptors, other signalling molecules and structural proteins linked to the actin cytoskeleton.

Silent synapse

A synapse that produces no detectable EPSP in the soma. Distal synapses might produce some local dendritic depolarization, but nevertheless be difficult to detect in the soma.

Input impedance

The resistance to the flow of current provided as an input to a neuron. This property depends on the resistance and capacitance of the structure (for example, the cell body or the dendritic spine) into which the input current is applied.

Dendritic spike

A spike initiated in the dendrites.

Action-potential threshold

The membrane potential at which an action potential is generated — usually approximately 20 mV above the resting potential.

Afterhyperpolarization

Membrane hyperpolarization following an action potential.

Afterdepolarization

Membrane depolarization following an action potential.

Hyperpolarization-activated cation channels

(HCN channels). Membrane cation channels that carry a current called Ih. The current is activated by hyperpolarization but causes depolarization. Some Ih is activated at rest, thus reducing input impedance and depolarizing the resting potential.

Backpropagating action potential

An action potential that is initiated in the axon and then propagates back into the dendrites.

Backpropagation-activated Ca2+ spike

(BAC spike). A spike that occurs in the distal apical dendrites of layer V pyramidal neurons during coincident synaptic stimulation and action-potential backpropagation.

Up and down states

Two distinct cortical states that are defined by relatively depolarized membrane potentials and lots of action-potential firing (the up state) versus hyperpolarized membrane potentials and very little firing (the down state). Although these states are often determined from the membrane potential in individual cells, groups of cells tend to transit between these states synchronously, so the state is a reflection of local cortical activity.

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Spruston, N. Pyramidal neurons: dendritic structure and synaptic integration. Nat Rev Neurosci 9, 206–221 (2008). https://doi.org/10.1038/nrn2286

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