The Ionic Mechanism of Membrane Potential Oscillations and Membrane Resonance in Striatal LTS Interneurons

Striatal low-threshold spiking (LTS) interneurons spontaneously transition to a depolarized, oscillating state similar to that seen after sodium channels are blocked. In the depolarized state, whether spontaneous or induced by sodium channel blockade, the neurons express a 3 - 7 Hz oscillation and membrane impedance resonance in the same frequency range. The membrane potential oscillation and membrane resonance are expressed in the same voltage range (> -40 mV). We identified and recorded from LTS interneurons in striatal slices from a mouse that expressed GFP under the control of the neuropeptide Y promoter. The membrane potential oscillation depended on voltage-gated calcium channels. Antagonism of CaV1 reduced the amplitude of the oscillation while blockade of CaV2.2 reduced the frequency. Both calcium sources activate a calcium-activated chloride current (CaCC), the blockade of which abolished the oscillation. Blocking any of these three channels abolished the membrane resonance. Immunohistochemical staining indicated ANO2, and not ANO1, as the CaCC source. Biophysical modeling showed that CaV1, CaV2.2 and ANO2 are sufficient to generate a membrane potential oscillation and membrane resonance, similar to that in LTS interneurons. LTS interneurons exhibit a membrane potential oscillation and membrane resonance that are both generated by CaV1 and CaV2.2 activating ANO2. They can spontaneously enter a state in which the membrane potential oscillation dominates the physiological properties of the neuron.