Key pointsr The superficial spinal dorsal horn contains a heterogeneous population of neurons that process sensory inputs.r Information on the properties of excitatory interneurons in this region is limited. As calretinin is a protein thought to be restricted to an excitatory population in this region, the aim of this study was to characterize calretinin-expressing neurons.r Most calretinin cells (85%) exhibited large A-type potassium currents and delayed firing action potential discharge, and received strong excitatory synaptic input, whereas the remainder exhibited hyperpolarization-activated cation currents and low threshold T-type calcium currents, and tonic-or initial bursting firing patterns, and received weak excitatory synaptic input. These respective features are consistent with properties of excitatory and inhibitory interneuron populations in this region of the spinal cord.r Our findings have resolved a previously unidentified population of inhibitory interneurons. Furthermore, the contrasting excitability patterns of excitatory and inhibitory calretinin-expressing neurons suggest that they play distinct roles in spinal sensory processing circuits.Abstract Neurons in the superficial dorsal horn (SDH) of the spinal cord play an important role in nociceptive, thermal, itch and light touch sensations. Excitatory interneurons comprise ß65% of all SDH neurons but surprisingly few studies have investigated their role in spinal sensory processing. Here we use a transgenic mouse to study putative excitatory SDH neurons that express the calcium binding protein calretinin (CR). Our immunocytochemical, morphological and electrophysiological analysis identified two distinct populations of CR-expressing neurons, which we termed 'Typical' and 'Atypical' . Typical CR-expressing neurons comprised ß85% of the population and exhibited characteristic excitatory interneuron properties including delayed firing discharge, large rapid A-type potassium currents, and central, radial or vertical cell morphologies. Atypical neurons exhibited properties consistent with inhibitory interneurons, including tonic firing or initial bursting discharge, I h currents, and islet cell morphology. Although both
Recent studies have revealed the essential role played by nerves in tumor progression. Nerves have been shown to infiltrate the tumor microenvironment and actively stimulate cancer cell growth and dissemination. This mechanism involves the release of neurotransmitters, such as catecholamines and acetylcholine, directly into the vicinity of cancer and stromal cells to activate corresponding membrane receptors. Conversely, the secretion of neurotrophic growth factors by cancer cells drives the outgrowth of nerves in solid tumors. This reciprocal interaction between nerves and cancer cells provides new insights into the cellular and molecular bases of tumorigenesis and points to the potential utility of antineurogenic therapies. This review will discuss our evolving understanding of the cross-talk between nerves and cancer cells. Cancer Res; 75(9);
Nerve dependence has long been described in animal regeneration, where the outgrowth of axons is necessary to the reconstitution of lost body parts and tissue remodeling in various species. Recent discoveries have demonstrated that denervation can suppress tumor growth and metastasis, pointing to nerve dependence in cancer. Regeneration and cancer share similarities in regard to the stimulatory role of nerves, and there are indications that the stem cell compartment is a preferred target of innervation. Thus, the neurobiology of cancer is an emerging discipline that opens new perspectives in oncology.
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