Contribution of presynaptic HCN channels to excitatory inputs of spinal substantia gelatinosa neurons

Peng, Sicong; Wu, Jing; Zhang, D.-Y.; Jiang, Changyu; Xie, Changan; Liu, T.

doi:10.1016/j.neuroscience.2017.06.046

Cited by 13 publications

(16 citation statements)

References 49 publications

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“…HCN4-immunoreactivity also showed a punctate staining pattern indicating that HCN4 was expressed on neurites or axon terminals. These findings were in line with those in previous reports [ 13 , 14 , 17 ].…”

Section: Resultssupporting

confidence: 94%

“…Glutamate is transported into the synaptic vesicle by VGLUT2 in presynaptic terminals of spinal excitatory interneurons and some myelinated, but not most unmyelinated, primary afferent fibers [ 29 ]. Therefore, to examine whether HCN4 is expressed in presynaptic terminals of excitatory interneurons, we next examined the colocalization of HCN4-IR signals and VGLUT2-IR signals [ 14 ]. In good agreement with a previous report [ 29 ], the VGLUT2-IR signals showed punctate patterns corresponding to axonal varicosities and were widely distributed in the SDH (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Among these terminals, the VGLUT2-immunoreactivity in those from unmyelinated afferents is weak while in those from interneurons are solid, and those from myelinated afferents forming synaptic glomeruli are larger than those from interneurons. Because some VGLUT2-IR terminals with HCN4-immunoreactivity were relatively small, our finding suggested that HCN4 was expressed in presynaptic terminals of a subset of excitatory interneurons [ 14 , 24 ]. The punctate HCN4-IR signals that did not overlap with VGLUT2-immunoreactivity might be located on dendrites of excitatory interneurons.…”

Section: Resultsmentioning

confidence: 99%

“…In the spinal cord, HCN channels are reportedly expressed in both the ventral and dorsal horns [ 11 – 14 ]. While some afferent information from the PNS is directly transmitted to projection neurons that have axons traveling to higher CNS regions, most of it is processed by the network of interneurons in the spinal dorsal horn (SDH) and then transmitted to projection neurons [ 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

“…It has been suggested that putative inhibitory PV cells express HCN4 because these cells present pronounced I h currents and high-frequency firing [ 17 ]. On the other hand, HCN4 is not likely colocalized with Pax2, a marker of inhibitory neurons, but is localized on presynaptic terminals of glutamatergic interneurons in the SDH [ 14 ]. In the present study, we carried out immunohistochemistry using double transgenic mice in which the expression level of HCN4 could be reversibly knocked down by doxycycline administration.…”

Section: Introductionmentioning

confidence: 99%

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Expression of the pacemaker channel HCN4 in excitatory interneurons in the dorsal horn of the murine spinal cord

et al. 2020

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In the central nervous system, hyperpolarization-activated, cyclic nucleotide-gated (HCN1–4) channels have been implicated in neuronal excitability and synaptic transmission. It has been reported that HCN channels are expressed in the spinal cord, but knowledge about their physiological roles, as well as their distribution profiles, appear to be limited. We generated a transgenic mouse in which the expression of HCN4 can be reversibly knocked down using a genetic tetracycline-dependent switch and conducted genetically validated immunohistochemistry for HCN4. We found that the somata of HCN4-immunoreactive (IR) cells were largely restricted to the ventral part of the inner lamina II and lamina III. Many of these cells were either parvalbumin- or protein kinase Cγ (PKCγ)-IR. By using two different mouse strains in which reporters are expressed only in inhibitory neurons, we determined that the vast majority of HCN4-IR cells were excitatory neurons. Mechanical and thermal noxious stimulation did not induce c-Fos expression in HCN4-IR cells. PKCγ-neurons in this area are known to play a pivotal role in the polysynaptic pathway between tactile afferents and nociceptive projection cells that contributes to tactile allodynia. Therefore, pharmacological and/or genetic manipulations of HCN4-expressing neurons may provide a novel therapeutic strategy for the pain relief of tactile allodynia.

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Section: Resultssupporting

confidence: 94%