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- 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 (CaV1) reduced the amplitude of the oscillation, whereas blockade of N-type calcium currents (CaV2.2) 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 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.

Generation and Preservation of the Slow Underlying Membrane Potential Oscillation in Model Bursting Neurons

The underlying membrane potential oscillation of both forced and endogenous slow-wave bursting cells affects the number of spikes per burst, which in turn affects outputs downstream. We use a biophysical model of a class of slow-wave bursting cells with six active currents to investigate and generalize correlations among maximal current conductances that might generate and preserve its underlying oscillation. We propose three phases for the underlying oscillation for this class of cells: generation, maintenance, and termination and suggest that different current modules coregulate to preserve the characteristics of each phase. Coregulation of IBurst and IA currents within distinct boundaries maintains the dynamics during the generation phase. Similarly, coregulation of ICaT and IKd maintains the peak and duration of the underlying oscillation, whereas the calcium-activated IKCa ensures appropriate termination of the oscillation and adjusts the duration independent of peak.

Coupled Oscillator Model of the Dopaminergic Neuron of the Substantia Nigra

Calcium imaging using fura-2 and whole cell recording revealed the effective location of the oscillator mechanism on dopaminergic neurons of the substantia nigra, pars compacta, in slices from rats aged 15–20 days. As previously reported, dopaminergic neurons fired in a slow rhythmic single spiking pattern. The underlying membrane potential oscillation survived blockade of sodium currents with TTX and was enhanced by blockade of voltage-sensitive potassium currents with TEA. Calcium levels increased during the subthreshold depolarizing phase of the membrane potential oscillation and peaked at the onset of the hyperpolarizing phase as expected if the pacemaker potential were due to a low-threshold calcium current and the hyperpolarizing phase to calcium-dependent potassium current. Calcium oscillations were synchronous in the dendrites and soma and were greater in the dendrites than in the soma. Average calcium levels in the dendrites overshot steady-state levels and decayed over the course of seconds after the oscillation was resumed after having been halted by hyperpolarizing currents. Average calcium levels in the soma increased slowly, taking many cycles to achieve steady state. Voltage clamp with calcium imaging revealed the voltage dependence of the somatic calcium current without the artifacts of incomplete spatial voltage control. This showed that the calcium current had little or no inactivation and was half-maximal at −40 to −30 mV. The time constant of calcium removal was measured by the return of calcium to resting levels and depended on diameter. The calcium sensitivity of the calcium-dependent potassium current was estimated by plotting the slow tail current against calcium concentration during the decay of calcium to resting levels at −60 mV. A single compartment model of the dopaminergic neuron consisting of a noninactivating low-threshold calcium current, a calcium-dependent potassium current, and a small leak current reproduced most features of the membrane potential oscillations. The same currents much more accurately reproduced the calcium transients when distributed uniformly along a tapering cable in a multicompartment model. This model represented the dopaminergic neuron as a set of electrically coupled oscillators with different natural frequencies. Each frequency was determined by the surface area to volume ratio of the compartment. This model could account for additional features of the dopaminergic neurons seen in slices, such as slow adaptation of oscillation frequency and may produce irregular firing under different coupling conditions.

Membrane Capacitance of Cortical Neurons and Glia During Sleep Oscillations and Spike-Wave Seizures

Dual intracellular recordings in vivo were used to disclose relationships between cortical neurons and glia during spontaneous slow (<1 Hz) sleep oscillations and spike-wave (SW) seizures in cat. Glial cells displayed a slow membrane potential oscillation (<1 Hz), in close synchrony with cortical neurons. In glia, each cycle of this oscillation was made of a round depolarizing potential of 1.5–3 mV. The depolarizing slope corresponded to a steady depolarization and sustained synaptic activity in neurons (duration, 0.5–0.8 s). The repolarization of the glial membrane (duration, 0.5–0.8 s) coincided with neuronal hyperpolarization, associated with disfacilitation, and suppressed synaptic activity in cortical networks. SW seizures in glial cells displayed phasic events, synchronized with neuronal paroxysmal potentials, superimposed on a plateau of depolarization, that lasted for the duration of the seizure. Measurements of the neuronal membrane capacitance during slow oscillating patterns showed small fluctuations around the resting values in relation to the phases of the slow oscillation. In contrast, the glial capacitance displayed a small-amplitude oscillation of 1–2 Hz, independent of phasic sleep and seizure activity. Additionally, in both cell types, SW seizures were associated with a modulatory, slower oscillation (≈0.2 Hz) and a persistent increase of capacitance, developing in parallel with the progression of the seizure. These capacitance variations were dependent on the severity of the seizure and the distance between the presumed seizure focus and the recording site. We suggest that the capacitance variations may reflect changes in the membrane surface area (swelling) and/or of the interglial communication via gap junctions, which may affect the synchronization and propagation of paroxysmal activities.

Maintenance of motor pattern phase relationships in the ventilatory system of the crab

The central pattern generator responsible for the gill ventilation rhythm in the shore crab Carcinus maenas can produce a functional motor pattern over a large (eightfold) range of cycle frequencies. One way to continue to generate a functional motor pattern over such a large frequency range would be to maintain the relative timing (phase) of the motor pattern as cycle frequency changes. This hypothesis was tested by measuring the phase of eight events in the motor pattern from extracellular recordings at different rhythm frequencies. The motor pattern was found to maintain relatively constant phase relationships among the various motor bursts in this rhythm over a large (sevenfold) range of cycle frequencies, although two phase-maintaining subgroups could be distinguished. Underlying this phase maintenance is a corresponding change in the time delay between events in the motor pattern ranging from 470 to 1800 ms over a sevenfold (300&shy;2100 ms) change in cycle period. Intracellular recordings from ventilatory neurons indicate that there is very little change in the membrane potential oscillation in the motor neurons with changes in cycle frequency. However, recordings from nonspiking interneurons in the ventilatory central pattern generator reveal that the rate of change of the membrane potential oscillation of these neurons varies in proportion to changes in cycle frequency. The strict biomechanical requirements for efficient pumping by the gill bailer, and the fact that work is performed in all phases of the motor pattern, may require that this motor pattern maintain phase at all rhythm frequencies.