(345) The Neuropeptide TLQP-62 Induces Calcium Transients in Primary Afferent Neurons

Abstract

The neurosecretory protein VGF (non-acronymic) is rapidly and robustly upregulated by primary somatosensory afferent neurons following peripheral nerve damage. VGF is proteolytically processed to yield a number of bioactive peptides, including the C-terminal peptide TLQP-62. Our work demonstrates that spinal TLQP-62 increases after nerve injury and that immunoneutralization of C-terminal VGF peptides attenuates the development of mechanical allodynia. This peptide has been shown to induce BDNF-dependent neuronal plasticity in the hippocampus. We have shown that TLQP-62 induces potentiation of glutamatergic responses in a subset of dorsal horn neurons and exposure of spinal cord slices to TLQP-62 increases TrkB phosphorylation, suggesting that TLQP-62 may facilitate BDNF release. Since primary afferent neurons are a potential source of spinal BDNF, we examined the effects of TLQP-62 on these neurons. Using mice that express a genetically encoded calcium indicator restricted to primary afferent neurons (Pirt-GCamp3 mice), we observed that TLQP-62 induced calcium transients in a subset of primary afferent fibers in the dorsal horn of spinal cord slices. The responses occurred immediately after TLQP-62 exposure and were sustained during prolonged exposure. TLQP-62 also induced calcium transients in DRG cultures, both in capsaicin-responsive neurites, as well as in neurites that did not respond to capsaicin. Ongoing work is investigating the functional consequences of these TLQP-62 effects and their relationship to BDNF via patch-clamp and BDNF-pHluorin imaging, respectively. Our observations of TLQP-62-induced calcium responses in the processes of primary afferent neurons are consistent with the idea that the peptide may modulate neurotransmitter release.