These may receive input from nonmyelinated sensory neurons, although it is possible that these inputs are indirect, as SCT dendrites seldom penetrate lamina II (Brown and Franz, 1969 and Cervero et al., 1977). Ultrastructural analysis of SCT dendrites reveals that they receive both excitatory and inhibitory

inputs, likely arising from hair follicle afferents and local inhibitory interneurons, respectively, with inhibitory inputs more commonly found on proximal dendrites. Furthermore, axoaxonic synapses or glomeruli are rarely found in apposition to SCT dendrites of the cat (Maxwell et al., 1991 and Maxwell et al., 1992). Thus, PSDC and SCT projection neurons are anatomically, morphologically, and physiologically distinct populations with regard to both presynaptic ABT-737 ic50 inputs and response properties. These two projection neuronal populations convey a mixed variety of modalities of ascending information, and compelling BAY 73-4506 evidence supports the notion that both PSDC and SCT neurons propagate integrated, processed cutaneous LTMR information to the brain. Thus, strong support

exists for a model in which the dorsal horn serves to integrate LTMR inputs and output projection neurons propagate this processed information to the brain. Major future goals should include defining the precise nature of direct and indirect LTMR inputs onto PSDC and SCT neurons and the relative contributions of LTMR subtypes to PSDC and SCT response properties. The morphological and physiological differences between the direct DC pathway and the indirect anterolateral, PSDC, and SCT pathways provide evidence

that these four main ascending systems subserve different roles in propagating tactile information from the periphery to the brain (Figure 5). Noxious and thermal stimuli Sodium butyrate are predominantly processed through the anterolateral pathway, although it is possible that anterolateral projection neurons serve an auxiliary role to the dorsal column pathway in sensory discrimination for stimuli in the noxious range. Certainly Aβ fibers that respond to a wide variety of tactile stimuli, such as myelinated nociceptors, may contribute to sensory discrimination of noxious mechanical stimuli. In another example, temperature-sensitive LTMRs, such as Aδ- and C-LTMRs, which respond to cooling of the skin, are likely to contribute to processing of thermal stimuli. For fine tactile discrimination tasks, much emphasis has been placed on the direct pathway whereby a subset of Aβ-LTMRs send direct projections through the dorsal columns to dorsal column nuclei, which in turn project forward to the thalamus and then to somatosensory cortex. However, we are beginning to appreciate how the physiological and anatomical complexity of the PSDC and SCT systems can be layered on top of the direct pathway to propagate touch information to higher processing centers, including the dorsal column nuclei and thalamus, where both systems converge (Figure 5).