The single dendritic branch as a fundamental functional unit in the nervous system
Introduction
In his classic Histology of the Nervous System, Ramon y Cajal asked “Why do dendritic trees even exist?” and concluded that “Dendrites exist solely to allow the cell to receive, and then transmit to the axon, the greatest variety of information from the most diverse sources.” [1]. This pioneering notion of dendrites as receivers of synaptic information was formalized as Cajal's ‘law of dynamic polarization’, postulating a unidirectional flow of information within the neuron. This view has been extensively characterized and has become widely established over the years. Experimental and modeling work in a variety of systems has provided strong evidence supporting the view that a major function of dendrites is to collect information from all connected input cells and transmit it to the site of action potential generation. However, it is now becoming increasingly clear that on top of their role as input receivers, dendrites orchestrate a variety of other processes – electrical, biochemical and cellular – that are fundamental to neuron physiology and circuit function. Furthermore, many of these processes seem to be highly compartmentalized at the level of individual dendritic branches, and the ‘variety of information’ alluded to by Cajal can already be locally processed within a single dendrite. Here we review recent work that supports the emerging notion that the single dendritic branch represents a major signalling unit—one that integrates electrical and chemical inputs, and can send independent output signals to a variety of targets.
Section snippets
Local electrical integration: signalling to the soma the result of a computation
Dendrites deliver electrical signals to the soma, but they are not just simple conductors of information. The passive and active properties of the dendritic tree are crucial for determining how electrical signals propagate, and define their compartmentalization and their interaction across different dendritic regions. Passive properties alone can act as a compartmentalizing force that acts in concert with the morphology to create electrical compartments on the level of dendritic branches,
Local dendritic release of neurotransmitters and neuromodulators—retrograde signalling of postynaptic activity
The results of dendritic computations can be passed on to the soma, where they are integrated to produce a pattern of action potential firing and neurotransmitter release by the axon, thus transmitting the local computations to other partners in the network. However, even this output step can be performed by dendritic branches alone, bypassing the soma and axon. Dendrites can release either classical neurotransmitters such as glutamate and GABA [19, 20], as well as neuromodulators like
Local chemical integration: biochemical signalling within the branch
Synaptic input can initiate complex cellular events and be effectively converted into and integrated as a biochemical signal (Figure 1c). A classic hallmark of this process is elevation of the local calcium concentration in the dendrite, with calcium either entering directly via the stimulated synapses or following activation of voltage-gated calcium channels, or a number of other possible second messenger pathways (see [27] for review). Calcium triggers a wide range of biochemical cascades,
Local plasticity—storage of local computations
Given the compartmentalization of biochemical signals within dendritic branches and their relationship with synaptic plasticity (especially for calcium), it is expected that single branches might also function as plasticity units (Figure 1d). This would imply that dendrites could be capable not only of performing individual computations, but also of locally storing them. One form of plasticity that was initially suggested to fulfil this prediction is plasticity of dendritic excitability, a
Local translation in dendrites—changing local dendritic structure and function
In the classical perspective, translation from mRNA to proteins happens at the soma, and freshly synthesized proteins are then shipped out to the appropriate locations in the dendrites. However, over the past two decades it has been shown that the entire translational machinery – polyribosomes, enzymes and associated membranous cisterns – is also present in dendrites, and that mRNA can be trafficked to dendrites. There is now very compelling evidence that these dendritic mRNAs can be used for
Conclusion
There is ample and growing evidence that dendritic branches can act as fundamental units of neuronal signalling. We have described how this argument is supported by the compartmentalization of various forms of signalling in dendrites – electrical, chemical, translational – on the scale of single branches. Such compartmentalization can arise simply by focal clustering of active synaptic input to the dendritic tree—which is easily achievable experimentally, but which has not yet been convincingly
References and recommended reading
Papers of particular interest, published within the annual period of review, have been highlighted as:
• of special interest
•• of outstanding interest
Acknowledgements
We are grateful to Mickey London and Arnd Roth for helpful discussions and comments on the manuscript. We thank the Wellcome Trust, European Research Council and the Gatsby Charitable Foundation for support.
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