Low‐fidelity GABA transmission within a dense excitatory network of the solitary tract nucleus

Key points•  Successful transmission of information to the brain relies on a balance of excitation and inhibition, and this balance is different across different brain regions. •  In the brain areas responsible for initiating homeostatic reflex control of visceral organs, excitation is known to be particularly powerful whereas inhibition is often less obvious. •  Using minimal focal activation of single axons, this study shows that elementary inhibitory transmission in this brainstem region is founded on an intrinsically weak process with limited transmitter release that is surprisingly prone to failures. •  Strong inhibitory transmission requires multi‐axon convergence of modestly reliable synapses, whereas primary afferent excitation arises from single, multi‐contact axons with highly reliable neurotransmitter release. •  The results suggest that the entry of primary afferent information along cranial nerves enjoys a high safety factor in part due to the fundamental weakness of inhibitory transmission at these initial central neurons.Abstract  Visceral primary afferents enter the CNS at the caudal solitary tract nucleus (NTS), and activate central pathways key to autonomic and homeostatic regulation. Excitatory transmission from primary solitary tract (ST)‐afferents consists of multiple contacts originating from single axons that offer a remarkably high probability of glutamate release and high safety factor for ST afferent excitation. ST afferent activation sometimes triggers polysynaptic GABAergic circuits, which feedback onto second‐order NTS neurons. Although inhibitory transmission is observed at second‐order neurons, much less is known about the organization and mechanisms regulating GABA transmission. Here, we used a focal pipette to deliver minimal stimulus shocks near second‐order NTS neurons in rat brainstem slices and directly activated single GABAergic axons. Most minimal focal shocks activated low jitter EPSCs from single axons with characteristics resembling ST afferents. Much less commonly (9% of sites), minimal focal shocks activated monosynaptic IPSCs at fixed latency (low jitter) that often failed (30%) and had no frequency‐dependent facilitation or depression. These GABA release characteristics contrasted markedly to the unfailing, large amplitudes for glutamate released during ST‐EPCSs recorded from the same neurons. Surprisingly, unitary GABAergic IPSCs were only weakly calcium dependent. In some neurons, strong focal shocks evoked compound IPSCs indicating convergent summation of multiple inhibitory axons. Our studies demonstrate that second‐order NTS neurons receive GABAergic transmission from a diffuse network of inhibitory axons that rely on an intrinsically less reliable and substantially weaker release apparatus than ST excitation. Effective inhibition depends on co‐activation of convergent inputs to blunt excitatory drive.