Modulation of respiratory frequency by peptidergic input to rhythmogenic neurons in the preBötzinger complex

Neurokinin-1 receptor (NK1R) and μ-opioid receptor (μOR) agonists affected respiratory rhythm when injected directly into the preBötzinger Complex (preBötC), the hypothesized site for respiratory rhythmogenesis in mammals. These effects were mediated by actions on preBötC rhythmogenic neurons. The distribution of NK1R(+) neurons anatomically defined the preBötC. Type 1 neurons in the preBötC, which have rhythmogenic properties, expressed both NK1Rs and μORs, whereas type 2 neurons expressed only NK1Rs. These findings suggest that the preBötC is a definable anatomic structure with unique physiological function and that a subpopulation of neurons expressing both NK1Rs and μORs generate respiratory rhythm and modulate respiratory frequency

Synaptic activity-independent persistent plasticity in endogenously active mammalian motoneurons

Potentiation and depression of glutamate receptor function in hippocampal, cerebellar, and cortical neurons are examples of persistent changes in synaptic function that underlie important behavioral adaptations such as learning and memory. Persistent changes in synaptic function relevant for motor behaviors have not been demonstrated in mammalian motoneurons. We demonstrate that adaptive changes in (±)-α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid hydrobromide (AMPA) receptor function at endogenously active synapses occur in motoneurons in neonatal rodents. We found a form of serotonin (5-HT)-dependent synaptic plasticity in hypoglossal (XII) motoneurons, which control tongue muscles affecting upper airway function, that is metamodulated by metabotropic glutamate receptors. Episodic, but not continuous, activation of postsynaptic 5-HT type 2 (5-HT(2)) receptors on hypoglossal (XII) motoneurons leads to long-lasting increases in their AMPA receptor-mediated respiratory drive currents and associated XII nerve motor output. Antagonism of group-I metabotropic glutamate receptors blocks induction of the 5-HT-induced increase in excitability. We propose that this activity-independent postsynaptic 5-HT-mediated plasticity represents the cellular mechanism underlying long-term facilitation, i.e., persistent increases in respiratory motor output and ventilation seen in humans and rodents in response to episodic hypoxia. Loss of activity in XII motoneurons is common during sleep causing snoring and, in serious cases, airway obstruction that interrupts breathing, a condition known as obstructive sleep apnea. These results may provide the basis for rationale development of therapeutics for obstructive sleep apnea in humans