Strong axonal GABAA channel activation increases voltage threshold. A: reverse fluorescence image of an Alexa Fluor–filled dentate granule neuron, with pipettes positioned for axon initial segment (AIS) and soma application of muscimol. Soma and AIS puffer pipettes are barely visible to the right of the cell and indicated by arrows. The whole cell recording pipette is indicated with an asterisk in the lumen, to the left of the soma. All 3 pipettes are outlined by dashed lines for clarity. Scale bar is 10 μm. B1: action potentials in response to current injections in the presence of muscimol (30 μM, red traces) interleaved with trials in the absence of muscimol (black traces). Muscimol applications started 50 ms before depolarizing current injection. Action potentials were elicited by 20 ms current injection from a resting potential of −70 mV. B2: from the same cell as in A1, responses to current injections in the presence (red traces) and absence (black traces) of interleaved somatic muscimol applications. B3: phase plot of control (black) and muscimol conditioned (red) action potentials shown in A1. Vm is membrane potential. Inset: voltage thresholds (Vt) as a function of sweep number. C: summary of voltage thresholds for control and muscimol conditions. Every symbol pair represents a single cell's average values for interleaved control and muscimol sweeps (n = 16). In this and subsequent figures, the open squares in the paired scatter plot represent the grand average of all the cells in the baseline and treatment conditions. Here and subsequent figures: *significantly different at the P < 0.05 level. D: representative traces used to obtain input resistance values. The arrow indicates the onset of a muscimol puff to either the AIS (red trace) or soma (blue trace), and the shift in baseline in the red trace before the voltage pulse results from the onset of GABAA receptor activation. The lower waveform gives the voltage protocol (mV values are given to the left). E: average input resistance for control, axonal, and somatic muscimol application (n = 4), shown in D.