Gabaergic Mechanisms In The Ventral Oral Pontine Tegmentum: The Rem Sleep-Induction Site - In The Modulation Of Sleep-Wake States

The ventral part of the oral pontine reticular nucleus (vRPO) is a nodal link in the neuronal network responsible for the generation and maintenance of rapid eye movement (REM) sleep and is reciprocally connected with structures involved in the control of wakefulness and non-REM (NREM) sleep. Shifting from one sleep state to another depends on the balance between excitation and inhibition in the reciprocal connections between these structures. Gamma-aminobutyric acid (GABA) occupies an outstanding place in these processes. In this review, we report the important role of GABA in vRPO function, specifying and discussing its location, origin, and role in this nucleus. Results from our laboratory revealed a few small GABA-immunoreactive cell bodies in vRPO; but we estimated that 30% of all vRPO synaptic terminals are actually immunoreactive to GABA. These inhibitory GABAergic terminals directly target somata and the different segments of the vRPO dendritic tree neurons. GABAergic terminals innervate serotonergic, GABAergic, and no-immunoreactive dendrites and terminals in the vRPO. Functionally, GABA elicits long-lasting hyperpolarizations of vRPO neurons in intracellular recording experiments in vitro. Small-volume microinjections of the GABA(A) receptor agonist muscimol in vRPO produce a statistically significant decrease of REM sleep proportions in freely moving cats. GABAergic axon terminals mainly originate in neurons located in diencephalic structures related with NREM sleep (such as the reticular thalamic nucleus) and wakefulness (such as the lateralposterior hypothalamus). These terminals would inhibit the vRPO REM "on" neurons either directly through postsynaptic mechanisms and/or indirectly through presynaptic inhibition of the excitatory terminals that form synapses with these neurons. Non-GABAergic and nonserotonergic terminals making asymmetric synapses (putatively excitatory) would indirectly inhibit REM "on" neurons through excitation of both serotonergic and GABAergic neurons, and terminals in the vRPO. Inhibition of GABAergic transmission in the vRPO contributes to the generation and maintenance of REM sleep.