Joseph A. Beatty, Soomin C. Song and Charles J. Wilson J Neurophysiol. 13(3):688-700.

Neurons respond to synaptic inputs in cell-type specific ways. Each neuron type may thus respond uniquely to shared patterns of synaptic input. We applied statistically identical barrages of artificial synaptic inputs to four striatal cell types to assess differences in their responses to a realistic input pattern. Each interneuron type fired in phase with a specific input frequency component. The fast-spiking interneuron fired in relation to the gamma-band (and higher) frequencies, the low-threshold spike interneuron to beta-band, and the cholinergic neurons to delta-band frequencies. Low-threshold spiking and cholinergic interneurons showed input impedance resonances at frequencies matching their spiking resonances.  Fast-spiking interneurons showed resonance of input impedance, but at lower than gamma frequencies.  The spiny projection neuron’s frequency preference did not have a fixed frequency, but instead tracked its own firing rate. Spiny cells showed no input impedance resonance.  Striatal interneurons are each tuned to a specific frequency band corresponding to the major frequency components of local field potentials. Their influence in the circuit may fluctuate along with the contribution of that frequency band to the input. In contrast, spiny neurons may tune to any of the frequency bands, by a change in firing rate.

Figure 1. Measurement of spiking resonance. A. Spectrum of the artificial synaptic barrage. B. Top panel: Filtered synaptic barrage (blue), and spike times (red lines). Inset at right shows how the phase of each spike time (φ) was measured relative to zero-crossings in the filtered waveforms. Bottom panel: corresponding trace of the original membrane potential. C. Calculation of Vector Strength by addition of vectors for each action potential. Vector Strength was scaled so that it ranges from 0 (no consistent phase-locking) to 1 (all spikes occurred at the same phase on the filtered waveform). D. Example spectrum of phase-locking consisting of vector strengths over a range of input frequencies.

Figure 2. Measurement of membrane resonance. A. An input voltage command. The frequency of the sinusoidal increased from 0 Hz at the start of the sweep to 40 Hz at the end. B. Corresponding membrane current. Resonance is apparent as a decrease in the current amplitude. C. Complex impedance locus uncorrected for access resistance (RA), (in red) and after correction (in black). The points increase in frequency going clockwise through the graph. D. Impedance amplitude spectrum obtained from the impedance (Z) measured at each frequency value in C.

Figure 3. Spiking resonance in FS neurons. A. FS cell after filling with Alexa 594 (electrode still present). B. Upper panel: High frequency stuttering response. Lower panel: A single episode of firing during the stuttering pattern, showing subthreshold oscillations. C-E. An example FS neuron with spiking resonance in the gamma range. C. Firing in short episodes of 40 spikes/s separated by brief silent periods. The minimum repetitive firing rate (fmin) is the modal instantaneous firing rate at rheobase. D. Upper panel: Artificial synaptic current barrage. Lower panel: Firing of the same neuron in C, at about the same rate, but made irregular by the presence of the artificial synaptic current barrage. E. Vector strength for phase-locking to the frequency components of the input barrage. Note the peak in phase-locking corresponds approximately to fmin. F-H, the same as C-E, but for another neuron with a much higher fmin. I. Histogram of fmin values for the sample of 16 FS neurons. J. Relationship between fmin and the peak of the vector strength curve (f0). K. Group resonance curve, frequency normalized to each cell’s f0. Error bars are SEM.

Figure 4. Membrane resonance in striatal FS neurons. A-C. Measurements from one neuron at 3 different holding potentials. A. Holding near the resting membrane potential reveals little or no resonance. B. Holding at a potential intermediate between the resting potential and threshold shows no resonance. C. Holding near threshold, at a potential corresponding to the silent period between episodes during stuttering, yields a strong resonance near 20 Hz. D. Average membrane resonance for the sample of FS neurons, normalized by the DC input resistance at each holding potential. Error bars are SEM.

Figure 5. Spiking resonance in LTS Neurons. A. An LTS cell after filling with Alexa 594 (electrode still present). B. The response of an LTS neuron to hyperpolarizing (black) and depolarizing (gray) current pulses. Note the presence of spontaneous firing and the rebound LTS afterhyperpolarization. C. Spiking resonance to artificial synaptic currents at the spontaneous firing rate (black) and at slower and faster rates. Maximal phase-locking occurs in the beta frequency range. D. Spiking resonance in the same cell in response to an artificial synaptic conductance barrage. E. Group curve for spiking resonance in all LTS cells studied. Error bars are SEM.

Figure 6. Membrane resonance in striatal LTS Interneurons. A-C. Impedance measurements from a neuron in control solution. A. Absence of resonance at a -80 mV. B. Resonance is also absent at -50 mV. C. Resonance in the beta range is present at a depolarized potential. D. Membrane resonance for the sample of LTS neurons in control solution, normalized for their low frequency (0.3 Hz) impedance. E-H. Membrane resonance in LTS cells is not abolished by TTX. E-G. An LTS cell after blockade of sodium channels with TTX. H. Group curve for the sample of neurons in TTX. Error bars are SEM.

Figure 7. Spiking and membrane resonance of cholinergic interneurons. A. Morphology of a cholinergic interneuron after filling with Alexa 594 at the end of the experiment (electrode still present). B. Responses of an ACh neuron in to depolarizing (gray) and hyperpolarizing (black) current pulses. Note hyperpolarizing sag response and rebound afterhyperpolarization, and spike frequency adaptation. C. Spiking resonance in the delta frequency range. D. Spiking resonance for the sample of ACh interneurons. E-F. Delta-frequency membrane resonance in an ACh interneuron at -80 mV (E) and at a more depolarized level near the firing threshold (F). G. Average membrane resonance at the two holding potentials for the sample of ACh cells. H. TTX-insensitivity of membrane potential resonance at -80 mV. I. Membrane resonance at -50 mV was abolished by TTX. Error bars are SEM

Figure 8. Firing-rate dependent phase-locking but absence of membrane resonance in spiny neurons. A. A spiny cell after filling with Alexa 594 (electrode still present). B. Responses of striatal spiny neurons to current pulses, including strong inward rectification and ramp-like depolarization preceding spiking. C. Spiking resonance in a spiny neuron to the artificial synaptic current barrage, at various firing rates. Peak of phase-locking occurs at the cell’s firing rate. D. Spiking resonance for the sample of spiny neurons at three different firing rates. E. Absence of membrane resonance at -80 mV (Down state). F. Absence of membrane resonance, but large TTX sensitivity of impedance at more depolarized but still subthreshold (Up state) membrane potentials. Error bars are SEM.