Fig. 7.

Postulated interaction of NTS presynaptic and postsynaptic NMDA receptors in intracellular signaling and control of food intake by hindbrain MC4 receptors. PKA-catalyzed phosphorylation of synapsin I in vagal afferent endings is downstream of both NMDAR and MC4R activation. Synapsin 1 phosphorylation increases the readily releasable pool of glutamatergic synaptic vesicles and is expected to result in increased vagal afferent synaptic strength and reduction of food intake. Activation of postsynaptic NMDAR and MC4R on NTS neurons is upstream of phosphorylation of ERK1/2 via PKA. ERK phosphorylation may result in additional protein phosphorylations and transcriptional changes in NTS neurons. Note that although activation of central vagal afferent endings contributes to reduction of food intake by MC4R activation (11), results reported here indicate that activation of vagal afferent endings is not required for activation of the ERK signaling cascade in NTS neurons in response to MC4R agonist application. In contrast, ERK phosphorylation in DMV neurons, following MC4R agonist application, depends upon the presence of intact vagal afferent endings.