Robustness to axon initial segment variation is explained by somatodendritic excitability in rat substantia nigra dopaminergic neurons (original) (raw)
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Characterization of the axon initial segment of mice substantia nigra dopaminergic neurons
The Journal of comparative neurology, 2017
The axon initial segment (AIS) is the site of initiation of action potentials and also influences action potential waveform, firing pattern and rate. In view of the fundamental aspects of motor function and behavior that depend on the firing of substantia nigra pars compacta (SNc) dopaminergic neurons, we identified and characterized their AIS in the mouse. Immunostaining for tyrosine hydroxylase (TH), sodium channels (Nav ) and ankyrin-G (Ank-G) was used to visualize the AIS of dopaminergic neurons. Reconstructions of sampled AIS of dopaminergic neurons revealed variable lengths (12 - 60 μm) and diameters (0.2 - 0.8 μm), and an average of 50% reduction in diameter between their widest and thinnest parts. Ultrastructural analysis revealed submembranous localization of Ank-G at nodes of Ranvier and AIS. Serial ultrathin section analysis and 3D reconstructions revealed that Ank-G colocalized with TH only at the AIS. Few cases of synaptic innervation of the AIS of dopaminergic neurons ...
Preserving axosomatic spiking features despite diverse dendritic morphology
Journal of Neurophysiology, 2013
Throughout the nervous system, cells belonging to a certain electrical class (e-class)–sharing high similarity in firing response properties–may nevertheless have widely variable dendritic morphologies. To quantify the effect of this morphological variability on the firing of layer 5 thick-tufted pyramidal cells (TTCs), a detailed conductance-based model was constructed for a three-dimensional reconstructed exemplar TTC. The model exhibited spike initiation in the axon and reproduced the characteristic features of individual spikes, as well as of the firing properties at the soma, as recorded in a population of TTCs in young Wistar rats. When using these model parameters over the population of 28 three-dimensional reconstructed TTCs, both axonal and somatic ion channel densities had to be scaled linearly with the conductance load imposed on each of these compartments. Otherwise, the firing of model cells deviated, sometimes very significantly, from the experimental variability of th...
Subcellular Patch-clamp Recordings from the Somatodendritic Domain of Nigral Dopamine Neurons
Journal of Visualized Experiments
Dendrites of dopaminergic neurons receive and convey synaptic input, support action potential back-propagation and neurotransmitter release. Understanding these fundamental functions will shed light on the information transfer in these neurons. Dendritic patch-clamp recordings provide the possibility to directly examine the electrical properties of dendrites and underlying voltage-gated ion channels. However, these fine structures are not easily accessible to patch pipettes because of their small diameter. This report describes a step-by-step procedure to collect stable and reliable recordings from the dendrites of dopaminergic neurons in acute slices. Electrophysiological measurements are combined with post hoc recovery of cell morphology. Successful experiments rely on improved preparation of slices, solutions and pipettes, adequate adjustment of the optics and stability of the pipette in contact with the recorded structure. Standard principles of somatic patch-clamp recording are applied to dendrites but with a gentler approach of the pipette. These versatile techniques can be implemented to address various questions concerning the excitable properties of dendrites. Video Link The video component of this article can be found at http://www.jove.com/video/54601/ 3 , the optics 4 and refinement of methods for slice preparation 5 during the last decades have enabled recordings from very thin (0.7-3 µm Ø) dendrites 6,7. These methods were, and are, still largely used to examine the excitability of dendrites in a variety of neurons 8. Direct dendritic recordings are essential to determine the distribution 9-19 and differences in the functional properties 20-22 of ion channels in distinct neuronal compartments. These data are the necessary complement of ion channel distributions detected with immunohistochemistry combined to light and electron microscopy 23,24. Dual somatodendritic recordings have been implemented to explore the propagation of action potentials 9,13-15,21,22,25-27 and spreading of synaptic potentials 13,16,18 along the somatodendritic domain of neurons, obtain detailed passive cable models 28-30 and investigate the temporal resolution of neuronal integration 31. The substantia nigra (SN) is a region located in the midbrain involved in several functions such as the control of movement, the coding of reward and habitual behaviors. The decrease of dopamine due to the specific loss of dopaminergic (DA) neurons in the SN is associated with the motor disturbances observed in patients suffering from Parkinson's disease 32. The nigral circuit is composed of two main cell types: dopaminergic and GABAergic neurons. Interestingly, these neurons have several specific features that distinguish them from other neurons. The axon of a large proportion of DA neurons and some GABA neurons originates from a dendritic site indicating that the dendritic arbor is heterogeneous (axonbearing and axon-lacking dendrites) 25,26,33. The morphology of these neurons contrasts therefore with the typical organization of neurons in which the information transfer follows the law of dynamic polarization emitted by Cajal: starting from dendrites, to soma and finally to axon 34. DA neurons are also known to release dopamine from their dendrites 35 , generate bursting activity 36 and NMDA-receptor plasticity 37. The dissection of these phenomena is elusive without direct recordings from the site where they are initiated. To gain insights into the relationship between the precise location and functional properties of ion channels and their role in the dendritic excitability and information transfer in nigral neurons, direct dendritic recordings are the method of choice. This report describes a detailed procedure that can be used to obtain single and dual patch-clamp recordings from dendrites of nigral neurons and the corresponding post hoc biocytin labeling. The basic principles for patching the somatic and the dendritic membrane are very similar. Practically however, recordings from dendritic sites require specific optimization in comparison to somatic recordings. Successful dendritic recordings rely on the quality of the slices, optimal adjustment of the optics, gentle approach of the patch pipette and stability of the recordings.
Neuroscience, 1983
Intracellular recordings from identified nigral dopamine neurons in the rat revealed that their potentials are composed of four components: (1) a slow depolarization, (2) an initial segment spike, (3) a somatodendritic spike, and (4) an afterhyperpolarization. By combining intracellular and extracellular recording techniques with anatomical studies using intracellular injections of Lucifer yellow, an attempt was made to localize each of these potentials to various neuronal compartments. Lucifer yellow injections demonstrated that the dopamine neurons recorded have a pyramidal or polygonal shaped soma, 12-30 pm in diameter, with 34 thick major dendrites which extend lO-50pm from the soma before bifurcating. The axon appears to rise from a major dendrite 15-30pm from the soma. Based on this anatomical configuration, results from the electrophysiological studies suggest that: (1) the slow depolarization is a pacemaker-like conductance most likely localized to the somatic region, (2) the initial segment spike is a low-threshold spike probably located at the axon hillock, (3) the somatodendritic spikes are long duration spikes that rapidly inactivate with depolarization, have a high threshold, and are localized to the dendritic regions. The action potential is then terminated by a long duration afterhyperpolarization. Our data further suggest that spike generation may be initiated by a slow depolarization at the soma triggering a spike in the low-threshold axon hillock which then spreads across the already-depolarized soma to trigger the dendritic spike.
Frontiers in Neural Circuits, 2021
The firing activity of ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) dopaminergic (DA) neurons is an important factor in shaping DA release and its role in motivated behavior. Dendrites in DA neurons are the main postsynaptic compartment and, along with cell body and axon initial segment, contribute to action potential generation and firing pattern. In this study, the organization of the dendritic domain in individual VTA and SNc DA neurons of adult male mice, and their relationship to in vivo spontaneous firing, are described. In comparison with dorsal VTA DA neurons, ventrally located VTA neurons (as measured by cell body location) possess a shorter total dendritic length and simpler dendritic architecture, and exhibit the most irregular in vivo firing patterns among DA neurons. In contrast, for DA neurons in the SNc, the higher irregularity of firing was related to a smaller dendritic domain, as measured by convex hull volumes. However, firing properties w...
Dendrites impact the encoding capabilities of the axon
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014
This study highlights a new and powerful direct impact of the dendritic tree (the input region of neurons) on the encoding capability of the axon (the output region). We show that the size of the dendritic arbors (its impedance load) strongly modulates the shape of the action potential (AP) onset at the axon initial segment; it is accelerated in neurons with larger dendritic surface area. AP onset rapidness is key in determining the capability of the axonal spikes to encode (phase lock to) rapid changes in synaptic inputs. Hence, our findings imply that neurons with larger dendritic arbors have improved encoding capabilities. This "dendritic size effect" was explored both analytically as well as numerically, in simplified and detailed models of 3D reconstructed layer 2/3 cortical pyramidal cells of rats and humans. The cutoff frequency of spikes phase locking to modulated inputs increased from 100 to 200 Hz in pyramidal cells of young rats to 400-600 Hz in human cells. In ...
Axonal initiation and active dendritic propagation of action potentials in substantia nigra neurons
Neuron, 1995
The site of action potential initiation in substantia nigra neurons was investigated by using simultaneous somatic and dendritic whole-cell recording in brain slices. In many dopamine neurons, action potentials were observed first at the dendritic recording site. Anatomical reconstruction showed that in these neurons, the axon emerged from the dendrite from which the recording had been made. Action potentials showed little attenuation in the dendritic tree, which in dopamine neurons was shown to be due to recruitment of dendritic sodium channels and may be related to the dendritic release of dopamine. We conclude that in substantia nigra neurons, the site of action potential initiation, and thus the final site of synaptic integration, is in the axon. As the axon can originate from a dendrite, up to 240 Fm away from the soma, synaptic input to the axon-bearing dendrite may be privileged with respect to its ability to influence action potential initiation.
The Journal of Physiology, 2015
The hyperpolarization-activated cation current I h is expressed in dopamine neurons of the substantia nigra, but the subcellular distribution of the current and its role in synaptic integration remain unknown. r We used cell-attached patch recordings to determine the localization profile of I h along the somatodendritic axis of nigral dopamine neurons in slices from young rats. r I h density is higher in axon-bearing dendrites, in a membrane area close to the axon origin, than in the soma and axon-lacking dendrites. r Dual current-clamp recordings revealed a similar contribution of I h to the waveform of single excitatory postsynaptic potentials throughout the somatodendritic domain. r The I h blocker ZD 7288 increased the temporal summation in all dendrites with a comparable effect in axon-and non-axon dendrites. r The strategic position of I h in the proximity of the axon may influence importantly transitions between pacemaker and bursting activities and consequently the downstream release of dopamine.
Cerebral Cortex, 2009
Interneurons in layer 2/3 (L2/3) of the somatosensory cortex show 4 types of axonal projection patterns with reference to the laminae and borders of columns in rat barrel cortex (Helmstaedter et al. 2008a). Here, we analyzed the dendritic geometry and electrical excitability of these interneurons. First, dendritic polarity, measured based on the insertion points of primary dendrites on the soma surface, yielded a continuous one-dimensional measure without a clustering of dendritic polarity types. Secondly, we analyzed polar and vertical distributions of dendritic length. A cluster analysis allowed the definition of 7 types of dendritic arborization. Thirdly, when dendritic polarity was related to the intrinsic electrical excitability we found that the ratio of frequency adaptation in trains of action potentials (APs) evoked by current injection was correlated with the number of primary dendrites. Numerical simulations of spiking patterns in L2/3 interneurons suggested that the number of primary dendrites could account for up to 50% of this correlation. Fourthly, dendritic arborization was not correlated with axonal projection, and axonal projection types could not be predicted by electrical excitability parameters. We conclude that 1) dendritic polarity is correlated to intrinsic electrical excitability, and 2) the axonal projection pattern represents an independent classifier of interneurons.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015
The axon initial segment (AIS) is a specialized structure near the start of the axon that is a site of neuronal plasticity. Changes in activity levels in vitro and in vivo can produce structural AIS changes in excitatory cells that have been linked to alterations in excitability, but these effects have never been described in inhibitory interneurons. In the mammalian olfactory bulb (OB), dopaminergic interneurons are particularly plastic, undergoing constitutive turnover throughout life and regulating tyrosine hydroxylase expression in an activity-dependent manner. Here we used dissociated cultures of rat and mouse OB to show that a subset of bulbar dopaminergic neurons possess an AIS and that these AIS-positive cells are morphologically and functionally distinct from their AIS-negative counterparts. Under baseline conditions, OB dopaminergic AISs were short and located distally along the axon but, in response to chronic 24 h depolarization, lengthened and relocated proximally towar...