Abstract
Recent work has shown that certain neurones have axonal GABA(A) receptors, whose tonic activation modifies their firing properties and neurotransmitter release capability. In addition, results obtained in interneurones of the molecular layer of the cerebellum indicate that action potential-released GABA binds back to the axon that released it, generating an autoreceptor current. In the present paper, we show that at physiological Cl(i)- concentration (15 mm) and at 34-36 degrees C, the autoreceptor current generates a large amplitude (up to 21 mV) after depolarization that lasts for about 150 ms, and that occasionally leads to double firing. Furthermore we show that elimination of the after depolarization, by either blocking GABA(A) receptors, or eliminating the autoreceptor currents through prolonged whole-cell recording, decreases burst firing. I(h) (a hyperpolarization-activated current) was previously found to be prominent in interneurone axons. We show that blocking I(h) leads to an increase in the amplitude of the autoreceptor current as well as of the associated after depolarization, suggesting a shunting effect of I(h) on autoreceptor-mediated after depolarization. Conversely, blocking I(h) accentuates burst firing. The effects of autoreceptor-mediated after depolarization on firing are prominent during a period of development when interneurone synapses are stabilized and vanish by postnatal day 17 (PN 17), together with the expression of the autoreceptor current. Altogether, this work reveals a new role for autoreceptors in the regulation of cell excitability and firing pattern, which may contribute to the development and stabilization of the cerebellar network.