Abstract Activation of presynaptic inhibitory receptors or high-frequency synaptic stimulation normally inhibits excitatory synaptic transmission by reducing transmitter release. We have explored the interactions between these two pathways for reducing synaptic strength and found that for synapses stimulated at high rates, agonists of the GABA B receptor become excitatory and strengthen transmission. At an auditory glutamatergic synapse featuring strong synaptic depression, the GABA B agonist baclofen reduced by 90% postsynaptic currents elicited at low frequency. By contrast, synaptic currents elicited at high frequencies were 5-fold larger in baclofen and had a markedly increased likelihood of firing well-timed postsynaptic action potentials. Presynaptic GABA B receptors may thus regulate transmitter release to enable sustained transmission at higher stimulus frequencies, thereby extending the dynamic range of neural circuits.