scholarly journals Kv3 channels contribute to the excitability of sub-populations of spinal cord neurons in lamina VII

2021 ◽  
Author(s):  
Pierce Mullen ◽  
Nadia Pilati ◽  
Charles H Large ◽  
Jim Deuchars ◽  
Susan A Deuchars
Keyword(s):  
Spinal Cord ◽  
Firing Frequency ◽  
Neuronal Firing ◽  
Recurrent Inhibition ◽  
Inhibitory Neurons ◽  
Spinal Cord Neurons ◽  
Lumbosacral Spinal Cord ◽  
Whole Cell Patch Clamp ◽  
Neuronal Types ◽  
Fast Firing

Autonomic parasympathetic preganglionic neurons (PGN) drive contraction of the bladder during micturition but remain quiescent during bladder filling. This quiescence is postulated to be due to recurrent inhibition of PGN by fast-firing adjoining interneurons. Here, we defined four distinct neuronal types within lamina VII of the lumbosacral spinal cord, where PGN are situated, by combining whole cell patch clamp recordings with k-means clustering of a range of electrophysiological parameters. Additional morphological analysis separated these neuronal classes into parasympathetic preganglionic populations (PGN) and a fast firing interneuronal population. Kv3 channels are voltage-gated potassium channels (Kv) that allow fast and precise firing of neurons. We found that blockade of Kv3 channels by tetraethylammonium (TEA) reduced neuronal firing frequency and isolated high-voltage-activated Kv currents in the fast-firing population but had no effect in PGN populations. Furthermore, Kv3 blockade potentiated the local and descending inhibitory inputs to PGN indicating that Kv3-expressing inhibitory neurons are synaptically connected to PGN. Taken together, our data reveal that Kv3 channels are crucial for fast and regulated neuronal output of a defined population that may be involved in intrinsic spinal bladder circuits that underpin recurrent inhibition of PGN.

Modulation of Intrinsic Spiking in Spinal Cord Neurons

2009 ◽  
Vol 102 (4) ◽  
pp. 2441-2452 ◽  
Author(s):  
Antonny Czarnecki ◽  
Vincent Magloire ◽  
Jürg Streit
Keyword(s):  
Spinal Cord ◽  
Cellular Level ◽  
Spiking Neurons ◽  
Synaptic Activity ◽  
Network Activity ◽  
Intrinsic Activity ◽  
Multielectrode Arrays ◽  
Synaptic Coupling ◽  
Spinal Cord Neurons ◽  
Whole Cell Patch Clamp

The vertebrate spinal cord is equipped with a number of neuronal networks that underlie repetitive patterns of behavior as locomotion. Activity in such networks is mediated not only by intrinsic cellular properties but also by synaptic coupling. In this study, we focused on the modulation of the intrinsic activity by 5-hydroxytryptamine (5-HT, serotonin) and the cholinergic agonist muscarine in spinal cord cultures (embryonic age 14 rats). We investigated theses cultures (slices and dissociated cells) at the network level using multielectrode arrays (MEAs) and at the cellular level using whole cell patch clamp. All cultures showed bursting network activity and intrinsic activity when γ-aminobutyric acid, glycine, and glutamate transmission was blocked. Using MEAs, we observed an increase of the intrinsic activity in the ventral part of the slices with 5-HT and muscarine. In single-cell recordings we found that 43 and 35% of the cells that were silent in the absence of fast synaptic activity were transformed into intrinsically spiking cells by 5-HT and muscarine, respectively. We tested the hypothesis that these neuromodulators act via modulation of the persistent sodium currents ( INaP) in these neurons. We found that 5-HT increased threefold the amplitude of INaP, specifically in the nonintrinsically spiking cells, and thus switched these cells into intrinsically spiking cells via activation of 5-HT2 receptor and the phospholipase C pathway. In contrast, the effect of muscarine on nonintrinsically spiking neurons seems to be independent of INaP. We conclude from these findings that serotoninergic and cholinergic modulation can turn silent into spontaneously spiking neurons and thus initiate new sources of activity for rhythm generation in spinal networks.

scholarly journals Visualization of Protein Aggregation in Nerve Cells After Ischemia/Reperfusion by Ubiquitin Immunohistochemistry and Impregnative Nauta Method

2004 ◽  
Vol 47 (3) ◽  
pp. 209-211
Author(s):  
Eva Mechírová ◽  
Iveta Domoráková ◽  
Marianna Feriková
Keyword(s):  
Spinal Cord ◽  
Protein Aggregation ◽  
Neuronal Death ◽  
Ischemia Reperfusion ◽  
Spinal Cord Ischemia ◽  
Ischemia And Reperfusion ◽  
Injured Spinal Cord ◽  
Spinal Cord Neurons ◽  
Lumbosacral Spinal Cord ◽  
Nauta Method

Using ubiquitin immunohistochemistry and impregnative Nauta method we demonstrated that ubiquitin positivity and Nauta positivity in the neurons affected with ischemic injury in the lumbosacral spinal cord of rabbits and dogs may be of the same origin. Increased number of ubiquitin-positive aggregates was found in the cytoplasm of neurons in the intermediate zone and lamina IX of ventral horns of spinal cord in rabbits after 30 min of ischemia followed by 24 h lasting reperfusion. Nauta-positive, flocculent, intracytoplasmic, dark clusters appeared in the same localization in the canine lumbosacral spinal cord neurons after 30 min of ischemia and 24 h of reperfusion. Ubiquitin aggregates and Nauta-positive dark clusters in the injured spinal cord neurons could be the first light microscopic signs of slow neuronal death following spinal cord ischemia and reperfusion.

Increased expression of spinal cord Fos protein induced by bladder stimulation after spinal cord injury

2000 ◽  
Vol 279 (1) ◽  
pp. R295-R305 ◽  
Author(s):  
Margaret A. Vizzard
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Afferent Pathways ◽  
Spinal Cord Neurons ◽  
Bladder Distension ◽  
Lumbosacral Spinal Cord ◽  
Fos Protein ◽  
Cord Injury ◽  
Bladder Afferents ◽  
Fos Expression

These studies examined Fos protein expression in spinal cord neurons synaptically activated by stimulation of bladder afferent pathways after spinal cord injury (SCI). In urethan-anesthetized Wistar rats after SCI for 6 wk, intravesical saline distension significantly ( P ≤ 0.005) increased the number of Fos-immunoreactive (IR) cells in the rostrolumbar (L1, 38 cells/section; L2, 29 cells/section) and caudal lumbosacral (L6, 140 cells/section; S1, 110 cells/section) spinal cord compared with control animals, but Fos expression in the L5 segment was not altered. The distribution of Fos-IR cells was also altered in the lumbosacral spinal cord. Significantly greater numbers of Fos-IR cells were distributed in the dorsal commissure and medial and lateral dorsal horn after intravesical distension in SCI animals. Large percentages of parasympathetic (75%) and sympathetic (85%) preganglionic neurons also expressed Fos-IR after intravesical distension in SCI animals. These results demonstrate that bladder distension produces increased numbers and an altered distribution pattern of Fos-IR cells after SCI. This pattern resembles that after noxious irritation of the bladder in control animals. Pretreatment with capsaicin significantly reduced the number of Fos-IR cells induced by bladder distension after SCI. These data suggest that SCI can reveal an altered Fos expression pattern in response to a nonnoxious bladder stimulus that is partially mediated by capsaicin-sensitive bladder afferents.

scholarly journals Characterization of Na+-Activated K+ Currents in Larval Lamprey Spinal Cord Neurons

2007 ◽  
Vol 97 (5) ◽  
pp. 3484-3493 ◽  
Author(s):  
Dietmar Hess ◽  
Evanthia Nanou ◽  
Abdeljabbar El Manira
Keyword(s):  
Spinal Cord ◽  
Action Potential ◽  
Feedback Mechanism ◽  
Neuronal Firing ◽  
Repetitive Firing ◽  
Spinal Cord Neurons ◽  
Negative Feedback Mechanism ◽  
Synaptic Interactions ◽  
Action Potential Waveform

Potassium channels play an important role in controlling neuronal firing and synaptic interactions. Na+-activated K+ ( KNa) channels have been shown to exist in neurons in different regions of the CNS, but their physiological function has been difficult to assess. In this study, we have examined if neurons in the spinal cord possess KNa currents. We used whole cell recordings from isolated spinal cord neurons in lamprey. These neurons display two different KNa currents. The first was transient and activated by the Na+ influx during the action potentials, and it was abolished when Na+ channels were blocked by tetrodotoxin. The second KNa current was sustained and persisted in tetrodotoxin. Both KNa currents were abolished when Na+ was substituted with choline or N-methyl-d-glucamine, indicating that they are indeed dependent on Na+ influx into neurons. When Na+ was substituted with Li+, the amplitude of the inward current was unchanged, whereas the transient KNa current was reduced but not abolished. This suggests that the transient KNa current is partially activated by Li+. These two KNa currents have different roles in controlling the action potential waveform. The transient KNa appears to act as a negative feedback mechanism sensing the Na+ influx underlying the action potential and may thus be critical for setting the amplitude and duration of the action potential. The sustained KNa current has a slow kinetic of activation and may underlie the slow Ca2+-independent afterhyperpolarization mediated by repetitive firing in lamprey spinal cord neurons.

scholarly journals Single-nucleus transcriptomic atlas of spinal cord neuron in human

2021 ◽  
Author(s):  
Donghang Zhang ◽  
Yiyong Wei ◽  
Jin Liu ◽  
Hongjun Chen ◽  
Jin Li ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Single Cell ◽  
Rna Sequencing ◽  
Marker Genes ◽  
Molecular Evidence ◽  
Functional Heterogeneity ◽  
Spinal Cord Neurons ◽  
Human Spinal Cord ◽  
Neuronal Types ◽  
Single Nucleus

Despite the recognized importance of spinal cord in sensory processing, motor behaviors and/or neural diseases, the underlying neuronal clusters remain elusive. Recently, several studies attempted to define the neuronal types and functional heterogeneity in spinal cord using single cell and/or single-nucleus RNA-sequencing in varied animal models. However, the molecular evidence of neuronal heterogeneity in human spinal cord has not been established yet. Here we sought to classify spinal cord neurons from human donors by high-throughput single-nucleus RNA-sequencing. The functional heterogeneity of identified cell types and signaling pathways that connecting neuronal subtypes were explored. Moreover, we also compared human results with previous single-cell transcriptomic profiles of mouse spinal cord. As a result, we generated the first comprehensive atlas of human spinal cord neurons and defined 18 neuronal clusters. In addition to identification of the new and functionally-distinct neuronal subtypes, our results also provide novel marker genes for previously known neuronal types. The comparation with mouse transcriptomic profiles revealed an overall similarity in the cellular composition of spinal cord between the two species. In summary, these results illustrate the complexity and diversity of neuronal types in human spinal cord and will provide an important resource for future researches to explore the molecular mechanism underlying several spinal cord physiology and diseases.

Ca2+-activated ion currents triggered by ryanodine receptor-mediated Ca2+release control firing of inhibitory neurons in the prepositus hypoglossi nucleus

2013 ◽  
Vol 109 (2) ◽  
pp. 389-404 ◽  
Author(s):  
Yasuhiko Saito ◽  
Yuchio Yanagawa
Keyword(s):  
Ryanodine Receptors ◽  
Smooth Muscles ◽  
Firing Frequency ◽  
Neuronal Firing ◽  
Inhibitory Neurons ◽  
Sk Channels ◽  
Spontaneous Firing ◽  
Central Neurons ◽  
Outward Currents ◽  
Prepositus Hypoglossi

Spontaneous miniature outward currents (SMOCs) are known to exist in smooth muscles and peripheral neurons, and evidence for the presence of SMOCs in central neurons has been accumulating. SMOCs in central neurons are induced through Ca2+-activated K+(KCa) channels, which are activated through Ca2+-induced Ca2+release from the endoplasmic reticulum via ryanodine receptors (RyRs). Previously, we found that some neurons in the prepositus hypoglossi nucleus (PHN) showed spontaneous outward currents (SOCs). In the present study, we used whole cell recordings in slice preparations of the rat brain stem to investigate the following: 1) the ionic mechanisms of SOCs, 2) the types of neurons exhibiting frequent SOCs, and 3) the effect of Ca2+-activated conductance on neuronal firing. Pharmacological analyses revealed that SOCs were induced via the activation of small-conductance-type KCa(SK) channels and RyRs, indicating that SOCs correspond to SMOCs. An analysis of the voltage responses to current pulses of the fluorescence-expressing inhibitory neurons of transgenic rats revealed that inhibitory neurons frequently exhibited SOCs. Abolition of SOCs via blockade of SK channels enhanced the frequency of spontaneous firing of inhibitory PHN neurons. However, abolition of SOCs via blockade of RyRs reduced the firing frequency and hyperpolarized the membrane potential. Similar reductions in firing frequency and hyperpolarization were also observed when Ca2+-activated nonselective cation (CAN) channels were blocked. These results suggest that, in inhibitory neurons in the PHN, Ca2+release via RyRs activates SK and CAN channels, and these channels regulate spontaneous firing in a complementary manner.

Regulation of neuronal specification in the zebrafish spinal cord by Delta function

Development ◽  
1998 ◽  
Vol 125 (3) ◽  
pp. 371-380 ◽  
Author(s):  
B. Appel ◽  
J.S. Eisen
Keyword(s):  
Spinal Cord ◽  
Lateral Inhibition ◽  
Delta Function ◽  
Cell Types ◽  
Dominant Negative ◽  
Spinal Cord Neurons ◽  
Local Environments ◽  
Dominant Negative Form ◽  
Neuronal Types ◽  
Local Cell

The vertebrate spinal cord consists of a large number of different cell types in close proximity to one another. The identities of these cells appear to be specified largely by information acquired from their local environments. We report here that local cell-cell interactions, mediated by zebrafish homologues of the Drosophila melanogaster neurogenic gene, Delta, regulate specification of diverse neuronal types in the ventral spinal cord. We describe identification of a novel zebrafish Delta gene expressed specifically in the nervous system and show, by expressing a dominant negative form of Delta protein in embryos, that Delta proteins mediate lateral inhibition in the zebrafish spinal cord. Furthermore, we find that Delta function is important for specification of a variety of spinal cord neurons, suggesting that lateral inhibition serves to diversify neuronal fate during development of the vertebrate spinal cord.

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