Glutamate is believed to be the primary neurotransmitter released by baroreceptor neurons in the medial nucleus tractus solitarius (mNTS). Many different subtypes of glutamate receptors have been localized to the mNTS, including both ionotropic and metabotropic glutamate receptors. Ionotropic receptors are involved in fast neurotransmission in various parts of the central nervous system, while metabotropic glutamate receptors have been shown to be involved in modulation of synaptic transmission. The integration of baroreceptor information is influenced by a number of factors, including the magnitude of afferent activity as well as both the duration and source of the afferent activity. It is hypothesized that baroreceptor neuron synaptic function is modulated by activation of metabotropic glutamate receptors within the mNTS. Subsequent alterations in mNTS neuronal activity may then modulate arterial baroreflex control of the sympathetic nervous system. Thus, metabotropic glutamate receptors may contribute to the change in baroreflex function associated with acute and chronic resetting, and with activation of cardiopulmonary receptors. The proposed studies will attempt to define a functional, integrative role for the metabotropic glutamate receptor (mGluR) in the modulation of arterial baroreflex function in the intact animal. There are 5 major and distinct aims: 1) To determine the role mGluRs in normal arterial baroreflex function, 2) To establish the role of mGluRs in baroreflex resetting following acute hypertension and hypotension, 3) To determine the role of mGluRs in chronic arterial baroreflex resetting due to hypertension, 4) To establish the role of mGluRs in the integration of reflex responses among baroreceptor afferents, 5) To determine neurophysiological effects of mGluR activation on baroreceptor modulation of neurons in the mNTS.
| Mueller, Patrick J; Foley, C Michael; Vogl, Helen W et al. (2005) Cardiovascular response to a group III mGluR agonist in NTS requires NMDA receptors. Am J Physiol Regul Integr Comp Physiol 289:R198-208 |
| Hoang, C J; Hay, M (2001) Expression of metabotropic glutamate receptors in nodose ganglia and the nucleus of the solitary tract. Am J Physiol Heart Circ Physiol 281:H457-62 |
| Foley, C M; Vogl, H W; Mueller, P J et al. (1999) Cardiovascular response to group I metabotropic glutamate receptor activation in NTS. Am J Physiol 276:R1469-78 |
| Foley, C M; Moffitt, J A; Hay, M et al. (1998) Glutamate in the nucleus of the solitary tract activates both ionotropic and metabotropic glutamate receptors. Am J Physiol 275:R1858-66 |
