Fast A‐type currents shape a rapidly adapting form of delayed short latency firing of excitatory superficial dorsal horn neurons that express the neuropeptide Y Y1 receptor

2021 ◽  
Author(s):  
Ghanshyam P. Sinha ◽  
Pranav Prasoon ◽  
Bret N. Smith ◽  
Bradley K. Taylor
Keyword(s):  
Neuropeptide Y ◽  
Dorsal Horn ◽  
Short Latency ◽  
Superficial Dorsal Horn ◽  
Dorsal Horn Neurons ◽  
Y1 Receptor

scholarly journals Fast A-type currents shape a rapidly adapting form of delayed short latency firing of excitatory superficial dorsal horn neurons that express the NPY Y1 receptor

2021 ◽  
Author(s):  
Ghanshyam P. Sinha ◽  
Pranav Prasoon ◽  
Bret N. Smith ◽  
Bradley K. Taylor
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Short Latency ◽  
Superficial Dorsal Horn ◽  
Firing Patterns ◽  
Future Studies ◽  
Dorsal Horn Neurons ◽  
Y1 Receptor ◽  
Reporter Mice ◽  
Rebound Spiking

ABSTRACTNeuroanatomical and behavioral evidence indicates that neuropeptide Y Y1 receptor-expressing interneurons (Y1-INs) in the superficial dorsal horn (SDH) are predominantly excitatory and contribute to chronic pain. Using an adult ex vivo spinal cord slice preparation from Y1eGFP reporter mice, we characterized firing patterns in response to steady state depolarizing current injection of GFP-positive cells in lamina II, the great majority of which expressed Y1 mRNA (88%). Randomly sampled and Y1eGFP neurons exhibited five firing patterns: tonic (TF), initial burst (IBF), phasic (PF), delayed short-latency <180 ms (DSLF), and delayed long-latency >180 ms (DLLF). When studied at resting membrane potential, most RS neurons exhibited delayed firing, while most Y1eGFP neurons exhibited phasic firing and not delayed firing. A preconditioning membrane hyperpolarization produced only subtle changes in the firing patterns of randomly sampled neurons, but dramatically shifted Y1eGFP neurons to DSLF (46%) and DLLF (24%). In contrast to randomly sampled DSLF neurons which rarely exhibited spike frequency adaptation, Y1eGFP DSLF neurons were almost always rapidly adapting, a characteristic of nociceptive-responsive SDH neurons. Rebound spiking was more prevalent in Y1eGFP neurons (6% RS vs 32% Y1eGFP), indicating enrichment of T-type calcium currents. Y1eGFP DSLF neurons exhibited fast A-type potassium currents that are known to delay or limit action potential firing, and these were of smaller current density as compared to randomly sampled DSLF neurons. Our results inspire future studies to determine whether tissue or nerve injury downregulates channels that contribute to A-currents, thus potentially unmasking T-type calcium channel activity and membrane hyperexcitability in Y1-INs, leading to persistent pain.KEYPOINTSNeuropeptide Y Y1 receptor-expressing neurons in the dorsal horn of the spinal cord contribute to chronic pain.For the first time, we characterized the firing patterns of Y1-expressing neurons in Y1eGFP reporter mice.Under hyperpolarized conditions, most Y1eGFP neurons exhibited fast A-type potassium currents and delayed, short-latency firing (DSLF).Y1eGFP DSLF neurons were almost always rapidly adapting and often exhibited rebound spiking, characteristics of spinal pain neurons under the control of T-type calcium channels.These results inspire future studies to determine whether tissue or nerve injury downregulates the channels that underlie A-currents, thus unmasking membrane hyperexcitability in Y1- expressing dorsal horn neurons, leading to persistent pain

scholarly journals Altered synaptic input and GABABreceptor function in spinal superficial dorsal horn neurons in rats with diabetic neuropathy

2007 ◽  
Vol 579 (3) ◽  
pp. 849-861 ◽  
Author(s):  
Xiu-Li Wang ◽  
Hong-Mei Zhang ◽  
Shao-Rui Chen ◽  
Hui-Lin Pan
Keyword(s):  
Diabetic Neuropathy ◽  
Dorsal Horn ◽  
Synaptic Input ◽  
Superficial Dorsal Horn ◽  
Dorsal Horn Neurons

Developmental Changes in the Fidelity and Short-Term Plasticity of GABAergic Synapses in the Neonatal Rat Dorsal Horn

2008 ◽  
Vol 99 (6) ◽  
pp. 3144-3150 ◽  
Author(s):  
Rachel A. Ingram ◽  
Maria Fitzgerald ◽  
Mark L. Baccei
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Receptive Fields ◽  
Neuronal Firing ◽  
Neonatal Rat ◽  
Superficial Dorsal Horn ◽  
Short Term ◽  
Dorsal Horn Neurons ◽  
Gabaergic Synapses

The lower thresholds and increased excitability of dorsal horn neurons in the neonatal rat suggest that inhibitory processing is less efficient in the immature spinal cord. This is unlikely to be explained by an absence of functional GABAergic inhibition because antagonism of γ-aminobutyric acid (GABA) type A receptors augments neuronal firing in vivo from the first days of life. However, it is possible that more subtle deficits in GABAergic signaling exist in the neonate, such as decreased reliability of transmission or greater depression during repetitive stimulation, both of which could influence the relative excitability of the immature spinal cord. To address this issue we examined monosynaptic GABAergic inputs onto superficial dorsal horn neurons using whole cell patch-clamp recordings made in spinal cord slices at a range of postnatal ages (P3, P10, and P21). The amplitudes of evoked inhibitory postsynaptic currents (IPSCs) were significantly lower and showed greater variability in younger animals, suggesting a lower fidelity of GABAergic signaling at early postnatal ages. Paired-pulse ratios were similar throughout the postnatal period, whereas trains of stimuli (1, 5, 10, and 20 Hz) revealed frequency-dependent short-term depression (STD) of IPSCs at all ages. Although the magnitude of STD did not differ between ages, the recovery from depression was significantly slower at immature GABAergic synapses. These properties may affect the integration of synaptic inputs within developing superficial dorsal horn neurons and thus contribute to their larger receptive fields and enhanced afterdischarge.

Five Sources of a Dorsal Root Potential: Their Interactions and Origins in the Superficial Dorsal Horn

1997 ◽  
Vol 78 (2) ◽  
pp. 860-871 ◽  
Author(s):  
Patrick D. Wall ◽  
Malcolm Lidierth
Keyword(s):  
Motor Cortex ◽  
Dorsal Horn ◽  
Dorsal Root ◽  
Repetitive Stimulation ◽  
Superficial Dorsal Horn ◽  
Dorsal Horn Neurons ◽  
Dorsal Roots ◽  
Myelinated Fibers ◽  
Root Potential ◽  
Stimulation Of

Wall, Patrick D. and Malcolm Lidierth. Five sources of a dorsal root potential: their interactions and origins in the superficial dorsal horn. J. Neurophysiol. 78: 860–871, 1997. The dorsal root potential (DRP) was measured on the lumbar dorsal roots of urethan anesthetized rats and evoked by stimulation of five separate inputs. In some experiments, the dorsal cord potential was recorded simultaneously. Stimulation of the L3 dorsal root produced a DRP on the L2 dorsal root containing the six components observed in the cat including the prolonged negative wave (DRP V of Lloyd 1952 ). A single shock to the myelinated fibers in the sural nerve produced a DRP on the L6 dorsal root after the arrival in the cord of the afferent volley. The shape of this DRP was similar to that produced by dorsal root stimulation. Repetitive stimulation of the myelinated fibers in the gastrocnemius nerve also produced a prolonged negative DRP on the L6 dorsal root. When a single stimulus (<5 μA; 200 μs) was applied through a microelectrode to the superficial Lissauer Tract (LT) at the border of the L2 and L3 spinal segments, a characteristic prolonged negative DRP (LT-DRP) began on the L2 dorsal root after some 15 ms. Stimulation of the LT evoked DRPs bilaterally. Recordings on nearby dorsal roots showed this DRP to be unaccompanied by stimulation of afferent fibers in those roots. The LT-DRP was unaffected by neonatal capsaicin treatment that destroyed most unmyelinated fibers. Measurements of myelinated fiber terminal excitability to microstimulation showed that the LT-DRP was accompanied by primary afferent depolarization. Repetitive stimulation through a microelectrode in sensorimotor cortex provoked a prolonged and delayed negative DRP (recorded L2–L4). Stimulation in the cortical arm area and recording on cervical dorsal roots showed that the DRP was evoked more from motor areas than sensory areas of cortex. Interactions were observed between the LT-DRP and that evoked from the sural or gastrocnemius nerves or motor cortex. The LT-DRP was inhibited by preceding stimulation of the other three sources but LT stimulation did not inhibit DRPs evoked from sural or gastrocnemius nerves on the L6 dorsal root or from motor cortex on the L3 root. However, LT stimulation did inhibit the DRP evoked by a subsequent Lissaeur tract stimulus. Recordings were made from superficial dorsal horn neurons. Covergence of input from LT sural, and gastrocnemius nerves and cortex was observed. Spike-triggered averaging was used to examine the relationship between the ongoing discharge of superficial dorsal horn neurons and the spontaneous DRP. The discharge of 81% of LT responsive cells was correlated with the DRP.

Superficial dorsal horn neurons with double spike activity in the rat

2007 ◽  
Vol 419 (2) ◽  
pp. 147-152 ◽  
Author(s):  
Gerardo Rojas-Piloni ◽  
Anthony H. Dickenson ◽  
Miguel Condés-Lara
Keyword(s):  
Dorsal Horn ◽  
Spike Activity ◽  
Superficial Dorsal Horn ◽  
Dorsal Horn Neurons

Ectopic HOXA5 expression results in abnormal differentiation, migration and p53-independent cell death of superficial dorsal horn neurons

2005 ◽  
Vol 159 (2) ◽  
pp. 87-97 ◽  
Author(s):  
Matthew A. Abbott ◽  
Milan Joksimovic ◽  
Christopher K. Tuggle
Keyword(s):  
Cell Death ◽  
Dorsal Horn ◽  
Superficial Dorsal Horn ◽  
Dorsal Horn Neurons

scholarly journals Excitability of Rat Superficial Dorsal Horn Neurons Following a Neonatal Immune Challenge

2018 ◽  
Vol 9 ◽  
Author(s):  
Melissa A. Tadros ◽  
Ihssane Zouikr ◽  
Deborah M. Hodgson ◽  
Robert J. Callister
Keyword(s):  
Dorsal Horn ◽  
Superficial Dorsal Horn ◽  
Immune Challenge ◽  
Dorsal Horn Neurons

ERK Integrates PKA and PKC Signaling in Superficial Dorsal Horn Neurons. I. Modulation of A-Type K+ Currents

2003 ◽  
Vol 90 (3) ◽  
pp. 1671-1679 ◽  
Author(s):  
Hui-Juan Hu ◽  
Kathi S. Glauner ◽  
Robert W. Gereau
Keyword(s):  
Protein Kinase ◽  
Dorsal Horn ◽  
Neuronal Excitability ◽  
Potassium Currents ◽  
Superficial Dorsal Horn ◽  
Dorsal Horn Neurons ◽  
Kinase C ◽  
Extracellular Signal ◽  
Whole Cell Recordings ◽  
K Currents

The transient outward potassium currents (also known as A-type currents or IA) are important determinants of neuronal excitability. In the brain, IA is modulated by protein kinase C (PKC), protein kinase A (PKA), and extracellular signal-related kinase (ERK), three kinases that have been shown to be critical modulators of nociception. We wanted to determine the effects of these kinases on IA in superficial dorsal horn neurons. Using whole cell recordings from cultured mouse spinal cord superficial dorsal horn neurons, we found that PKC and PKA both inhibit IA in these cells, and that PKC has a tonic inhibitory action on IA. Further, we provide evidence supporting the hypothesis that PKC and PKA do not modulate IA directly, but rather act as upstream activators of ERKs, which modulate IA. These results suggest that ERKs serve as signal integrators in modulation of IA in dorsal horn neurons and that modulation of A-type potassium currents may underlie aspects of central sensitization mediated by PKC, PKA, and ERKs.

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