Combined Changes in Chloride Regulation and Neuronal Excitability Enable Primary Afferent Depolarization to Elicit Spiking without Compromising its Inhibitory Effects
Fig 3
PAD-induced repetitive spiking in DRG neurons.
(A) Sample traces from a typical neuron showing that 4-AP had the intended effect of enabling repetitive spiking in response to current injection (Istim, top traces), yet virtual GABA conductance continued to elicit only transient spiking (bottom traces). EGABA = -20 mV. Scale bar for gGABA in all panels show nS before and after normalization by membrane capacitance of the recorded cell. (B) Responses from another neuron showing that increasing ḡGABA across a very broad range (an order of magnitude greater than required for transient spiking) failed to eventually induce repetitive spiking. Instead, spike amplitude was attenuated and membrane potential was effectively clamped near EGABA after the initial spike. (C) To further increase excitability, dynamic clamp was used to insert a virtual voltage-dependent sodium conductance (ḡNa = 0.2 nS/pF) after applying 4-AP. The effectiveness of this manipulation is clear from the development of spontaneous spiking (right panels). Under these conditions, a slow gGABA waveform or gGABA step induced repetitive spiking. The result was observed in 2 of 2 neurons tested.