The cutaneous primary afferents from the upper trunk and forelimbs reach the medial cuneate nucleus in their way towards the cerebral cortex. The aim of this work was twofold: (i) to study the mechanisms used by the primary afferents to relay cutaneous information to cuneate cuneolemniscal (CL) and noncuneolemniscal (nCL) cells, and (ii) to determine the intracuneate mechanisms leading to the elaboration of the output signal by CL cells. Extracellular recordings combined with microiontophoresis demonstrated that the primary afferent cutaneous information is communicated to CL and nCL cells through AMPA, NMDA and kainate receptors. These receptors were sequentially activated: AMPA receptors participated mainly during the initial phase of the response, whereas kainate- and NMDA-mediated activity predominated during a later phase. The involvement of NMDA receptors was confirmed by in vivo intracellular recordings. The cutaneous-evoked activation of CL cells was decreased by GABA and increased by glycine acting at a strychnine-sensitive site, indicating that glycine indirectly affects CL cells. Two subgroups of nCL cells were distinguished based on their sensitivity to iontophoretic ejection of glycine and strychnine. Overall, the results support a model whereby the primary afferent cutaneous input induces a centre-surround antagonism in the cuneate nucleus by activating (via AMPA, NMDA and kainate receptors) and disinhibiting (via serial glycinergic-GABAergic interactions) a population of CL cells with overlapped receptive fields that at the same time inhibit (via GABAergic cells) other neighbouring CL cells with different receptive fields.