Distribution of N-methyl-D-aspartate and non-N-methyl-D-aspartate glutamate receptor subunits on respiratory motor and premotor neurons in the rat

Abstract

Glutamate is required for the transmission of inspiratory drive in respiratory premotor and motor neurons. The glutamate receptors (GluRs) responsible for this essential function have yet to be anatomically characterized. We mapped the GluR subtypes expressed by respiratory premotor and motor neurons by using combined immunohistochemistry and retrograde labeling in adult rats. Phrenic motoneurons and bulbospinal ventral respiratory group (VRG) neurons were retrogradely labeled and immunolabeled with subunit-specific antibodies against the N-methyl-D-aspartate (NMDA) receptor subtype (NMDAR1) and the non-NMDA receptor subtypes, alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA; GluR1, GluR2/3, GluR4) and kainate (GluR5-7). Phrenic motoneurons and bulbospinal VRG neurons showed positive immunolabeling for all five GluR subunits. These results support the hypothesis that NMDA and non-NMDA receptor subtypes underlie the excitation of bulbospinal VRG neurons and phrenic motoneurons. Furthermore, immunolabeling for each receptor subtype demonstrated a unique distribution along the neuronal membrane. Immunoreactivity for AMPA receptor subunits was distributed throughout somata and proximal dendrites, NMDAR1 subunit immunolabeling was localized to somata, and GluR5-7 subunit immunolabeling was confined largely to dendrites. The differential distribution of AMPA, kainate, and NMDA receptors on the somal and dendritic surface of respiratory neurons suggests that the location of glutamatergic synapses along the neuronal surface is an important determinant of glutamate-mediated postsynaptic currents. Consequently, different patterns of glutamatergic excitation of respiratory neurons could be achieved by selective activation of different profiles of GluR subtypes on different portions of the neuronal membrane.

Functional recovery after cervical spinal cord injury: Role of neurotrophin and glutamatergic signaling in phrenic motoneurons

“…Glutamate NMDA and AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionate) receptors are present on phrenic motoneurons (Chitravanshi and Sapru, 1996; Dong and Feldman, 1999; Robinson and Ellenberger, 1997). A distinguishing feature of ionotropic NMDA receptors is that glutamate binding and post-synaptic depolarization activates the receptor and allows Ca 2+ to flow through the cell membrane along with the cations Na + and K + (Alpert and Alford).…”

Vesicular Glutamate Transporter 2 Is Required for Central Respiratory Rhythm Generation But Not for Locomotor Central Pattern Generation

“…It is located in the rostroventrolateral medulla and relies on excitatory glutamatergic connections (Funk et al, 1993;Rekling and Feldman, 1998). PBC interneurons discharge through activation of NMDA and non-NMDA glutamate receptors (Funk et al, 1993(Funk et al, , 1997 and are immunopositive for glutamate receptor subunits (Robinson and Ellenberger, 1997;Paarmann et al, 2005). Neurokinin-1-receptor (NK1R)-expressing PBC neurons, essential for maintenance of normal breathing in vivo (Gray et al, 2001;McKay et al, 2005), have been shown to contain Vglut2 mRNA and to receive VGLUT2-positive terminals (Gray et al, 1999;Guyenet et al, 2002;Stornetta et al, 2003a,b) but also have GABAergic and glycinergic terminals (Liu et al, 2002).…”

Diversity of Functional Astroglial Properties in the Respiratory Network

“…It follows that extracellular potassium (Rybak et al, 2003) and glutamate will control neuronal bursting by setting and modulating the membrane potential. Indeed, abundant expression of different ionotropic and metabotropic glutamate receptors has been described for the brainstem (Robinson and Ellenberger, 1997;Dong and Feldman, 1999).…”