Figure 8.

Schematic representation of the fever central pathways. a, The new model for fever pathways is represented by the schematic figure at the top panel. During infectious and inflammatory conditions, PGE2 acts via EP3 inhibitory receptors (red) expressed in the MnPO^Vglut2 and VLPO^Vglut2 neurons that project directly to DMH and RPa (green lines) to produce fever. We hypothesize that the MnPO^Vglut2 neurons that express EP3R are probably inhibited during a fever response, and innervate inhibitory interneurons in the DMH and RPa (red), thus disinhibiting the excitatory DHA and RPa thermogenic neurons. b, The widely influential Morrison and Nakamura (2019) model hypothesized EP3R expression by MnPO^GABA neurons that directly disinhibit thermogenic excitatory DHA and RPa neurons (green) during fever responses. CC, corpus callosum; ILC, infralimbic cortex; IML, intermediolateral cell column; OB, olfactory bulb; Och, Optic chiasm; OVLT, organum vasculosum of the lamina terminalis; 4V, fourth ventricle.