The ionic mechanism of membrane potential oscillations and membrane resonance in striatal LTS interneurons

Abstract

Striatal low-threshold spiking (LTS) interneurons spontaneously transition between spiking and a persistently depolarized state. In the depolarized state, the neurons express a 3- to 7-Hz oscillation and membrane impedance resonance. The membrane potential oscillation depends on both L- and N-type calcium currents. Both calcium sources activate a calcium-activated chloride current, which provides the restorative current for the oscillation and resonance. Striatal LTS cells express anoctamin 2 (ANO2), and not ANO1, calcium-activated chloride channels .

Abstract

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- to 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 (greater than −40 mV). We identified and recorded from LTS interneurons in striatal slices from a mouse that expressed green fluorescent protein under the control of the neuropeptide Y promoter. The membrane potential oscillation depended on voltage-gated calcium channels. Antagonism of L-type calcium currents (Ca _V1) reduced the amplitude of the oscillation, whereas blockade of N-type calcium currents (Ca _V2.2) reduced the frequency. Both calcium sources activate a calcium-activated chloride current (CaCC), the blockade of which abolished the oscillation. The blocking of any of these three channels abolished the membrane resonance. Immunohistochemical staining indicated anoctamin 2 (ANO2), and not ANO1, as the CaCC source. Biophysical modeling showed that Ca _V1, Ca _V2.2, 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 Ca _V1 and Ca _V2.2 activating ANO2. They can spontaneously enter a state in which the membrane potential oscillation dominates the physiological properties of the neuron.