ReviewDendritic integration in pyramidal neurons during network activity 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.
References (140)
- et al.
Subcellular topography of visually driven dendritic activity in the vertebrate visual system
Neuron
(2009) - et al.
Synaptic integration gradients in single cortical pyramidal cell dendrites
Neuron
(2011) - et al.
Fetal alcohol syndrome: historical perspectives
Neurosci. Biobehav. Rev.
(2007) - et al.
Linear summation of excitatory inputs by CA1 pyramidal neurons
Neuron
(1999) - et al.
CaMKII regulation in information processing and storage
Trends Neurosci.
(2012) - et al.
Variations in GABRA2, encoding the alpha 2 subunit of the GABA(A) receptor, are associated with alcohol dependence and with brain oscillations
Am. J. Hum. Genet.
(2004) - et al.
Decreased numbers of dendritic spines on cortical pyramidal neurons in human chronic alcoholism
Neurosci. Lett.
(1986) - et al.
Dendritic spine pathology: cause or consequence of neurological disorders?
Brain Res. Brain Res. Rev.
(2002) - et al.
Granule cell dispersion in temporal lobe epilepsy is associated with changes in dendritic orientation and spine distribution
Exp. Neurol.
(2011) - et al.
Effects of prenatal ethanol exposure on dendritic spines of layer V pyramidal neurons in the somatosensory cortex of the rat
J. Neurol. Sci.
(1987)
Brief seizures cause dendritic injury
Neurobiol. Dis.
AMPAR removal underlies Abeta-induced synaptic depression and dendritic spine loss
Neuron
Increased NMDA responses and dendritic degeneration in human epileptic hippocampal neurons in slices
Neurosci. Lett.
Active dendrites: colorful wings of the mysterious butterflies
Trends Neurosci.
Spatiotemporal dynamics of epileptiform propagations: imaging of human brain slices
Neuroimage
Deletion of FMR1 in Purkinje cells enhances parallel fiber LTD, enlarges spines, and attenuates cerebellar eyelid conditioning in fragile X syndrome
Neuron
NMDA receptors and schizophrenia
Curr. Opin. Pharmacol.
Abeta plaques lead to aberrant regulation of calcium homeostasis in vivo resulting in structural and functional disruption of neuronal networks
Neuron
A cellular mechanism for cortical associations: an organizing principle for the cerebral cortex
Trends Neurosci.
Synaptic clustering by dendritic signalling mechanisms
Curr. Opin. Neurobiol.
Soluble oligomers of amyloid beta protein facilitate hippocampal long-term depression by disrupting neuronal glutamate uptake
Neuron
Integrative properties of radial oblique dendrites in hippocampal CA1 pyramidal neurons
Neuron
Selective loss of GABA neurons in area CA1 of the rat hippocampus after intraventricular kainate
Epilepsy Res.
Inhibitory control of linear and supralinear dendritic excitation in CA1 pyramidal neurons
Neuron
Cocaine-induced proliferation of dendritic spines in nucleus accumbens is dependent on the activity of cyclin-dependent kinase-5
Neuroscience
Prefrontal dopamine D1 receptors and working memory in schizophrenia
J. Neurosci.
Submillisecond precision of the input–output transformation function mediated by fast sodium dendritic spikes in basal dendrites of CA1 pyramidal neurons
J. Neurosci.
Petilla terminology: nomenclature of features of GABAergic interneurons of the cerebral cortex
Nat. Rev. Neurosci.
Acquired dendritic channelopathy in temporal lobe epilepsy
Science
Neuronal activity regulates diffusion across the neck of dendritic spines
Science
Dendritic discrimination of temporal input sequences in cortical neurons
Science
Estructura de los centros nerviosos de las aves
Rev. Trim. Histol. Norm. Patol.
Input summation by cultured pyramidal neurons is linear and position-independent
J. Neurosci.
Backward cortical projections to primary somatosensory cortex in rats extend long horizontal axons in layer I
J. Comp. Neurol.
An increase in persistent sodium current contributes to intrinsic neuronal bursting after status epilepticus
J. Neurophysiol.
Functional mapping of single spines in cortical neurons in vivo
Nature
Compartmentalization of GABAergic inhibition by dendritic spines
Science
Natural oligomers of the amyloid-beta protein specifically disrupt cognitive function
Nat. Neurosci.
Abnormal dendritic spines in fragile X knockout mice: maturation and pruning deficits
Proc. Natl. Acad. Sci. U.S.A.
Dendritic but not somatic GABAergic inhibition is decreased in experimental epilepsy
Nat. Neurosci.
Specific abnormalities in serotonin release in the prefrontal cortex of isolation-reared rats measured during behavioural performance of a task assessing visuospatial attention and impulsivity
Psychopharmacology (Berl.)
Distribution and patterns of connectivity of interneurons containing calbindin, calretinin, and parvalbumin in visual areas of the occipital and temporal lobes of the macaque monkey
J. Comp. Neurol.
Untersuchungen ueber Gehirn und Rueckenmark des Menschen und der Saeugethiere
Genetic enhancement of thalamocortical network activity by elevating alpha 1g-mediated low-voltage-activated calcium current induces pure absence epilepsy
J. Neurosci.
Distributed hierarchical processing in the primate cerebral cortex
Cereb. Cortex
Down's syndrome and Alzheimer's disease: dendritic spine counts in the hippocampus
Acta Neuropathol.
State-dependent dendritic computation in hippocampal CA1 pyramidal neurons
J. Neurosci.
On the initiation and propagation of dendritic spikes in CA1 pyramidal neurons
J. Neurosci.
Decreased dendritic spine density on prefrontal cortical pyramidal neurons in schizophrenia
Arch. Gen. Psychiatry
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2022, Seminars in Cell and Developmental BiologyCitation Excerpt :For example, rhythmic whisker stimulation was shown to efficiently induce synaptic LTP in L2/3 pyramidal neurons in the absence of somatic spikes [41]. The plasticity instead depends on the occurrence of NMDAR-mediated long-lasting dendritic depolarizations, which bear similarities to dendritic plateau potentials [41,83,84,121,122]. In the sensory-evoked LTP study, long-lasting NMDAR-mediated depolarizations were elicited by feedback signals originating in the POm of the thalamus [41,123].
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2021, iScienceCitation Excerpt :In this study, we observed that changes in network connectivity strength were associated with alteration of dendritic spine density, which is commonly perceived as the morphological correlate of synaptic inter-neuronal communication (Arnsten et al., 2010). Indeed, correlative changes in network connectivity as well as spine density or morphology have been demonstrated in a number of brain disorders including Alzheimer's disease, epilepsy, and psychiatric diseases (Palmer, 2014; Penzes et al., 2011). Besides these primary brain disorders, changes in spine density and morphology have also been observed in previous reports investigating GF mice in comparison to conventionally colonized animals (Luczynski et al., 2016).
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