Elsevier

Brain Research Bulletin

Volume 103, April 2014, Pages 2-10
Brain Research Bulletin

Review
Dendritic integration in pyramidal neurons during network activity and disease

https://doi.org/10.1016/j.brainresbull.2013.09.010Get rights and content

Highlights

  • Review on dendritic integration and the resulting linear or non-linear processing.

  • Examples are given from both in vitro and in vivo investigations.

  • Description of the changes in dendritic integration during different neuropathological diseases.

  • Discussions about dendritic spine function, ion channel characteristics and inhibition in the diseased state.

  • Highlights from reported abnormalities that effect dendritic integrative properties.

Abstract

Neurons have intricate dendritic morphologies which come in an array of shapes and sizes. Not only do they give neurons their unique appearance, but dendrites also endow neurons with the ability to receive and transform synaptic inputs. We now have a wealth of information about the functioning of dendrites which suggests that the integration of synaptic inputs is highly dependent on both dendritic properties and neuronal input patterns. It has been shown that dendrites can perform non-linear processing, actively transforming synaptic input into Na+ spikes, Ca2+ plateau spikes and NMDA spikes. These membrane non-linearities can have a large impact on the neuronal output and have been shown to be regulated by numerous factors including synaptic inhibition. Many neuropathological diseases involve changes in how dendrites receive and package synaptic input by altering dendritic spine characteristics, ion channel expression and the inhibitory control of dendrites. This review focuses on the role of dendrites in integrating and transforming input and what goes wrong in the case of neuropathological diseases.

This article is part of a Special Issue entitled ‘Dendrites and Disease’.

Introduction

The task of understanding how neurons translate input to output is central to explaining brain function. Since the majority of inputs arrive at the dendrites of neurons, it is critical to understand the processing performed by dendritic trees which leads to action potential output. This can be achieved by looking at different levels of detail in a single neuron, from the activity in a dendritic spine to the functioning of an entire dendritic arbor (Fig. 1). Historically, even though dendrites of various neurons were shown to have active membranes (Llinas et al., 1968, Kuno and Llinas, 1970), dendrites were often treated as non-active structures that collected synaptic signals and relayed them passively to the axonal action potential initiation zone. However, it is now well established that dendrites have active conductances which support various processes and non-linear input transformations (for a review, see Johnston and Narayanan, 2008).

Dendrites (and axons) were first described by Deiters (1865). Since then, dendrites have been further characterized according to their morphological characteristics (Fig. 1a). The different pyramidal neuron dendritic areas (basal, oblique, apical, tuft) are often located in spatially distinct brain layers and they therefore receive different input streams of information. For example, the basal dendrites of cortical pyramidal neurons receive the majority of synaptic inputs (Larkman, 1991) which largely carry feed forward information (Felleman and Van Essen, 1991). Conversely, the tuft dendrites receive long-range feedback input from other cortical areas and the thalamus including the posterior medial nucleus (POm) of the thalamus (Rubio-Garrido et al., 2009), the secondary somatosensory cortex (Cauller et al., 1998) and parahippocampal structures (Witter and Groenewegen, 1986). How, and even whether, these different pathways are integrated at the cellular level by dendritic processes has been the source of debate for decades.

Despite their central role in cellular processing of information, our understanding of dendritic functioning has lagged behind other fields of neuroscience research. This is largely due to the difficulty in recording from the very thin dendritic structures, which are often less than 1 μm in diameter. However, recent advances in imaging techniques have now opened this field of research. This review will examine how dendrites integrate and transform synaptic input and how this process is affected during neurological diseases. Firstly, the different levels of dendritic integration and the resulting linear or non-linear processing will be discussed with the use of both in vitro and in vivo examples. Alterations in dendritic integration during different neuropathological diseases will then be explored, including the influence of changes in dendritic spine morphology and function, ion channel phosphorylation and expression and dendritic inhibition. Lastly, the role of the prefrontal cortex in disease will be briefly discussed. This is not designed to be an exhaustive review of all the changes that occur in neurons during neuropathological diseases, but highlights a few of the reported abnormalities that have drastic effects on dendritic integrative properties. Since much is known about the computation and integrative properties of pyramidal neuron dendrites, namely cortical and hippocampal neurons, this review focuses mainly on these cell types.

Section snippets

Dendritic integration

In seminal work over half a century ago, Rall described the electrical properties of dendrites and showed that passive dendritic filtering properties prolong the time window for synaptic summation of distal inputs (Rall, 1967, Rall et al., 1967, Rall and Rinzel, 1973). Rall's computational theories predicted that the dendritic site of synaptic input could greatly influence the integrative properties of dendrites. Although the dendrites of neurons have subsequentially been shown not to be

What can go wrong with dendritic integration in the diseased brain?

Considering dendritic integration is central to neuronal function, it is not surprising that many forms of mental retardation and disease are associated with dendritic dysfunction (Fig. 3a). Several dendritic deficits reported in neurological disorders, including abnormalities in spines, ion channels and inhibition, are discussed below.

Conclusion

The process of dendritic integration is not straightforward and has been a source of much debate and intense investigation ever since “the integrative action of the nervous system” was first postulated by Sherrington in 1906. Despite common belief that dendrites were simply cables which passively relayed information from synaptic sites to the axonal action potential initiation zone, the intensive role dendrites play in transforming information is just starting to be realized. Both in vitro and

Conflict of interest

There are no competing conflicts of interest.

Acknowledgments

I would like to acknowledge Matthew Larkum, Rogier Min, Sean Murphy and Adam Shai for their helpful comments on the manuscript.

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