- Title
- Functional and Molecular Analysis of Proprioceptive Sensory Neuron Excitability in Mice
- Creator
- Madden, Jessica F.; Davis, Olivia C.; Boyle, Kieran A.; Iredale, Jacqueline A.; Browne, Tyler J.; Callister, Robert J.; Smith, Douglas W.; Jobling, Phillip; Hughes, David I.; Graham, Brett A.
- Relation
- NHMRC.631000 http://purl.org/au-research/grants/nhmrc/631000 & 1043933 http://purl.org/au-research/grants/nhmrc/1043933 & 1184974 http://purl.org/au-research/grants/nhmrc/1144638 & 1184974 http://purl.org/au-research/grants/nhmrc/1114974
- Relation
- Frontiers in Molecular Neuroscience Vol. 13, Issue May 2020, no. 36, p. 1-13
- Publisher Link
- http://dx.doi.org/10.3389/fnmol.2020.00036
- Publisher
- Frontiers Research Foundation
- Resource Type
- journal article
- Date
- 2020
- Description
- Neurons located in dorsal root ganglia (DRG) are crucial for transmitting peripheral sensations such as proprioception, touch, temperature, and nociception to the spinal cord before propagating these signals to higher brain structures. To date, difficulty in identifying modality-specific DRG neurons has limited our ability to study specific populations in detail. As the calcium-binding protein parvalbumin (PV) is a neurochemical marker for proprioceptive DRG cells we used a transgenic mouse line expressing green fluorescent protein (GFP) in PV positive DRGs, to study the functional and molecular properties of putative proprioceptive neurons. Immunolabeled DRGs showed a 100% overlap between GFP positive (GFP+) and PV positive cells, confirming the PVeGFP mouse accurately labeled PV neurons. Targeted patch-clamp recording from isolated GFP+ and GFP negative (GFP−) neurons showed the passive membrane properties of the two groups were similar, however, their active properties differed markedly. All GFP+ neurons fired a single spike in response to sustained current injection and their action potentials (APs) had faster rise times, lower thresholds and shorter half widths. A hyperpolarization-activated current (Ih) was observed in all GFP+ neurons but was infrequently noted in the GFP− population (100% vs. 11%). For GFP+ neurons, Ih activation rates varied markedly, suggesting differences in the underlying hyperpolarization-activated cyclic nucleotide-gated channel (HCN) subunit expression responsible for the current kinetics. Furthermore, quantitative polymerase chain reaction (qPCR) showed the HCN subunits 2, 1, and 4 mRNA (in that order) was more abundant in GFP+ neurons, while HCN 3 was more highly expressed in GFP− neurons. Likewise, immunolabeling confirmed HCN 1, 2, and 4 protein expression in GFP+ neurons. In summary, certain functional properties of GFP+ and GFP− cells differ markedly, providing evidence for modality-specific signaling between the two groups. However, the GFP+ DRG population demonstrates considerable internal heterogeneity when hyperpolarization-activated cyclic nucleotide-gated channel (HCN channel) properties and subunit expression are considered. We propose this heterogeneity reflects the existence of different peripheral receptors such as tendon organs, muscle spindles or mechanoreceptors in the putative proprioceptive neuron population.
- Subject
- parvalbumin; proprioception; dorsal root ganglia; sensory neuron; action potential; HCN channel
- Identifier
- http://hdl.handle.net/1959.13/1441412
- Identifier
- uon:41419
- Identifier
- ISSN:1662-5099
- Language
- eng
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