Axon-Carrying Dendrites Convey Privileged Synaptic Input in Hippocampal Neurons

Thome, Christian; Kelly, T.; Yanez, Antonio; Schultz, Christian; Engelhardt, Maren; Cambridge, Sidney B.; Both, Martin; Draguhn, Andreas; Beck, Hanno; Egorov, Alexei V.

doi:10.1016/j.neuron.2014.08.013

Cited by 102 publications

(136 citation statements)

References 56 publications

(81 reference statements)

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“…1). These observations are in line with earlier reports using Golgi staining or EM from layer 2/3 or 5 pyramidal cells in a range of different cortical areas and species (19,22,23) or in hippocampal pyramidal neurons (20,21) and support the notion that variation in axon location is a common principle of the cellular architecture of pyramidal cells. Cable theory predicts that the axial resistance between the AIS and the soma has a strong impact on spike initiation (11).…”

Section: Discussionsupporting

confidence: 92%

“…These observations of invariable somatic APs are in agreement with recordings in hippocampal CA1 pyramidal neurons with AIS distances ranging between ∼1.0 and 20 μm showing little, if any, difference in the somatic AP (21). In that study, it was shown that axon coupling to basal dendrites facilitates synapse-evoked dendritic spike generation in the axon-carrying dendrite (21). Although we did not examine the presence of local basal dendritic spikes, our integrated electrophysiological and morphological approach suggests that the anatomical arrangement may rather serve geometrical homeostasis, normalizing the amplitude and rise time of the somatic AP.…”

Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 86%

“…In fact, an axon origin from a dendrite is even a defining feature of some hippocampal interneurons (19,20). Furthermore, about 30 to 60% of the pyramidal neurons in the hippocampus have an axon emerging from a basal (or sometimes, an apical) dendrite up to ∼40-μm distance from the soma (20,21), and also, in the neocortex, axons have been observed to emerge from basal dendrites (19,22,23). Here, we investigated whether AIS location plays a functional role in neocortical pyramidal neuron excitability.…”

mentioning

confidence: 99%

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Covariation of axon initial segment location and dendritic tree normalizes the somatic action potential

Hamada

Goethals

Vries

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

121

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In mammalian neurons, the axon initial segment (AIS) electrically connects the somatodendritic compartment with the axon and converts the incoming synaptic voltage changes into a temporally precise action potential (AP) output code. Although axons often emanate directly from the soma, they may also originate more distally from a dendrite, the implications of which are not wellunderstood. Here, we show that one-third of the thick-tufted layer 5 pyramidal neurons have an axon originating from a dendrite and are characterized by a reduced dendritic complexity and thinner main apical dendrite. Unexpectedly, the rising phase of somatic APs is electrically indistinguishable between neurons with a somatic or a dendritic axon origin. Cable analysis of the neurons indicated that the axonal axial current is inversely proportional to the AIS distance, denoting the path length between the soma and the start of the AIS, and to produce invariant somatic APs, it must scale with the local somatodendritic capacitance. In agreement, AIS distance inversely correlates with the apical dendrite diameter, and model simulations confirmed that the covariation suffices to normalize the somatic AP waveform. Therefore, in pyramidal neurons, the AIS location is finely tuned with the somatodendritic capacitive load, serving as a homeostatic regulation of the somatic AP in the face of diverse neuronal morphologies.T he axon initial segment (AIS) specifies in vertebrate neurons a single domain for the final integration of synaptic input and the initiation of action potentials (APs) (1, 2). To rapidly produce large inward and outward currents mediating the AP, the AIS contains a complex arrangement of cytoskeletal and transmembrane proteins clustering high densities of voltage-gated sodium (Nav) and potassium (Kv) channels in the axolemma (2-4). Although the composition of ion channels is critical for initiation and regulation of firing patterns, there are emerging insights that the AIS is not operating in isolation but is also subject to activity-dependent changes in size and location constrained by the local dendritic branch geometry and the passive cable properties (5-7). Experimental studies linking changes in AIS length and neuronal output showed that an increased length facilitates AP generation (6,8). In these cases, the net increased excitability is a logical consequence of the larger Nav conductance. However, predicting the impact of AIS location on neuronal output is more complex. Experimental studies showed that an activity-dependent distal shift of the AIS is associated with decreased AP output (5). In contrast, model simulations showed that shifting the AIS distally promotes excitability (9). One of the critical factors influencing AIS excitability is the large somatodendritic membrane area acting as current sink for sodium current generated in the AIS (10-12). In this view, a distal anatomical location of the AIS increases electrical compartmentalization and facilitates axonal AP generation. Indeed, the local depolarization in the...

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 86%

mentioning

confidence: 99%

See 2 more Smart Citations

Covariation of axon initial segment location and dendritic tree normalizes the somatic action potential

Hamada

Goethals

Vries

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

121

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“…This observation enforces earlier results of computer simulations (Lee et al, 2005) and suggestions that both the distal and proximal part of the dendrite giving rise to an axon may have very important roles in the regulation of action potential initiation. Indeed, with the help of modern techniques, in a recent study authors provided functional evidence for the influence of dendritic axon origin on action potential initiation (Thome et al, 2014).…”

Section: Axon Architecture Of Neurons Outside the Superficial Dorsal mentioning

confidence: 99%

Neurons in the lateral part of the lumbar spinal cord show distinct novel axon trajectories and are excited by short propriospinal ascending inputs

et al. 2015

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Order of Authors Secondary Information:The role of spinal dorsal horn propriospinal connections in nociceptive processing is not yet established. Recently described, rostrocaudally oriented axon collaterals of lamina I projection and local-circuit neurons (PNs and LCNs) running in the dorsolateral funiculus (DLF) may serve as the anatomical substrate for intersegmental processing. Putative targets of these axons include lateral dendrites of superficial dorsal horn neurons, including PNs, and also neurons in the lateral spinal nucleus (LSN) that are thought to be important integrator units receiving, among others, visceral sensory information. Here we used an intact spinal cord preparation to study intersegmental connections within the lateral part of the superficial dorsal horn. We detected brief monosynaptic and prolonged polysynaptic excitation of lamina I and LSN neurons when stimulating individual dorsal horn neurons located caudally, even in neighbouring spinal cord segments. These connections, however, were infrequent. We also revealed that some projection neurons outside the dorsal grey matter and in the LSN have distinct, previously undescribed course of their projection axon. Our findings indicate that axon collaterals of lamina I PNs and LCNs in the DLF rarely form functional connections with other lamina I and LSN neurons and that the majority of their targets are on other elements of the dorsal horn. The unique axon trajectories of neurons in the dorsolateral aspect of the spinal cord, including the LSN do not fit our present understanding of midline axon guidance and suggest that their function and development differ from the neurons inside lamina I. These findings emphasize the importance of understanding the connectivity matrix of the superficial dorsal horn in order to decipher spinal sensory information processing. Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation Answers to Reviewer 1First of all, the authors would like to thank Reviewer 1 for his constructive comments and suggestions that helped us improving the manuscript. Below we give detailed answers to all major and minor concerns raised. Major issues 1)We completely agree with the reviewer that the statistical analysis would have helped to make our conclusions on morphometric parameters stronger. The reason why we decided to talk about the tendencies only without statistical tests was the low number of the reconstructed neurons in the groups. However, since we observed and wanted to demonstrate the difference between neurons within and outside lamina I (in the adjacent lateral white matter), in this revised version we pooled projection neurons (PNs) and localcircuit neurons (LCNs) from our previous reports to form a group of cells in lamina I called "L-I" whereas neurons lateral to the edge of the dorsal horn and in the LSN are now referred to as "OUT/LSN". Statistical analyses were performed between these two groups and showed significant differences in the morphometric parameters investigated, with the...

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The Axon Initial Segment is the Dominant Contributor to the Neuron's Extracellular Electrical Potential Landscape

et al. 2018

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Extracellular voltage fields, produced by a neuron’s action potentials, provide a widely used means for studying neuronal and neuronal-network function. The neuron’s soma and dendrites are thought to drive the extracellular action potential (EAP) landscape, while the axon’s contribution is usually considered less important. However, by recording voltages of single neurons in dissociated rat cortical cultures and Purkinje cells in acute mouse cerebellar slices through hundreds of densely packed electrodes, it is found, instead, that the axon initial segment dominates the measured EAP landscape, and, surprisingly, the soma only contributes to a minor extent. As expected, the recorded dominant signal has negative polarity (charge entering the cell) and initiates at the distal end. Interestingly, signals with positive polarity (charge exiting the cell) occur near some but not all dendritic branches and occur after a delay. Such basic knowledge about which neuronal compartments contribute to the extracellular voltage landscape is important for interpreting results from all electrical readout schemes. Finally, initiation of the electrical activity at the distal end of the axon initial segment (AIS) and subsequent spreading into the axon proper and backward through the proximal AIS toward the soma are confirmed. The corresponding extracellular waveforms across different neuronal compartments could be tracked.

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Axon-Carrying Dendrites Convey Privileged Synaptic Input in Hippocampal Neurons

Cited by 102 publications

References 56 publications

Covariation of axon initial segment location and dendritic tree normalizes the somatic action potential

Covariation of axon initial segment location and dendritic tree normalizes the somatic action potential

Neurons in the lateral part of the lumbar spinal cord show distinct novel axon trajectories and are excited by short propriospinal ascending inputs

The Axon Initial Segment is the Dominant Contributor to the Neuron's Extracellular Electrical Potential Landscape

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