Reduction of menthol-sensitive afferent inputs to superficial dorsal neurons in knockout mice of cadherin-8

Abstract

To elucidate how primary afferents responding to specific sensory modalities are sorted and connected with their target dorsal horn (DH) neurons, synaptic responses evoked in DH neurons were compared between wild and cadherin-8 (cad8, a cell-cell adhesion molecule) knockout mice. Cad8 was expressed by restricted populations of superficial DH neurons and small-diameter neurons in dorsal root ganglion, the majority of which co-expressed TRPM8. The amplitude of EPSCs evoked in superficial DH neurons by the activation of slow-conducting fibers in cad8 -/- mice was significantly smaller than that in wild mice. In cad8-expressing DH neurons, CNQX-sensitive fast and slow miniature EPSCs were elicited in the same cells. Menthol selectively increased the frequency of the slow mEPSCs. However, this effect was not observed in cad8 -/- mice. On the other hand, no differences were found in the amplitude of [Ca²⁺]i in small DRG neurons in response to menthol and in the facilitation of miniature release by capsaicin between wild and cad8-/- mice. The present results suggest that menthol-sensitive (TRPM8-expressing) afferent fibers transmit cool sensation to superficial DH neurons through Cad8-expressing synapses and Cad8 has an essential role in determining of the synaptic connectivity. [J Physiol Sci. 2007;57 Suppl:S102]