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The Journal of Neuroscience, February 21, 2007, 27(8):2112-2123; doi:10.1523/JNEUROSCI.5266-06.2007

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Cellular/Molecular
A Developmental Switch to GABAergic Inhibition Dependent on Increases in Kv1-Type K⁺ Currents

MacKenzie A. Howard, R. Michael Burger, and Edwin W Rubel

Department of Physiology and Biophysics and Virginia Merrill Bloedel Hearing Research Center, University of Washington, Seattle, Washington 98195

Correspondence should be addressed to Dr. Edwin W Rubel, Virginia Merrill Bloedel Hearing Research Center, University of Washington, Box 357923, Seattle, WA 98195. Email: rubel{at}u.washington.edu

Mature nucleus magnocellularis (NM) neurons, the avian homolog of bushy cells of the mammalian anteroventral cochlear nucleus, maintain high [Cl^–]_i and depolarize in response to GABA. Depolarizing GABAergic postsynaptic potentials (GPSPs) activate both the synaptic conductance and large outward currents, which, when coupled together, inhibit spikes via shunting and spike threshold accommodation. We studied the maturation of the synaptic and voltage-dependent components of inhibition in embryonic NM neurons using whole-cell and gramicidin-perforated patch-clamp techniques to measure Cl^– reversal potential, GABAergic synaptic responses, and voltage-dependent outward currents. We found that GABA enhanced excitability in immature NM neurons, undergoing a switch to inhibitory between embryonic day 14 (E14) and E18. Low-voltage-activated Kv1-type (dendrotoxin-I sensitive) K⁺ currents increased in amplitude between E14 and E18, whereas Cl^– reversal potential and synaptic conductances remained relatively stable during this period. GABA was rendered inhibitory because of this increase in low-voltage activated outward currents. GPSPs summed with other inputs to increase spike probability at E14. GPSPs shunted spikes at E18, but blocking Kv1 channels transformed this inhibition to excitation, similar to E14 neurons. Subthreshold depolarizing current steps, designed to activate outward currents similar to depolarizing GPSPs, enhanced excitability at E14 but inhibited spiking in E18 neurons. Blocking Kv1 channels reversed this effect, rendering current steps excitatory. We present the novel finding that the developmental transition of GABAergic processing from increasing neuronal excitability to inhibiting spiking can depend on changes in the expression of voltage-gated channels rather than on a change in Cl^– reversal potential.

Key words: inhibition; development; auditory; magnocellularis; potassium; GABA

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Received June 1, 2006; revised Jan. 18, 2007; accepted Jan. 24, 2007.

Correspondence should be addressed to Dr. Edwin W Rubel, Virginia Merrill Bloedel Hearing Research Center, University of Washington, Box 357923, Seattle, WA 98195. Email: rubel{at}u.washington.edu

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