Complex autonomous firing patterns of striatal low-threshold spike interneurons

Abstract

During sensorimotor learning, tonically active neurons (TANs) in the striatum acquire bursts and pauses in their firing based on the salience of the stimulus. Striatal cholinergic interneurons display tonic intrinsic firing, even in the absence of synaptic input, that resembles TAN activity seen in vivo. However, whether there are other striatal neurons among the group identified as TANs is unknown. We used transgenic mice expressing green fluorescent protein under control of neuronal nitric oxide synthase or neuropeptide-Y promoters to aid in identifying low-threshold spike (LTS) interneurons in brain slices. We found that these neurons exhibit autonomous firing consisting of spontaneous transitions between regular, irregular, and burst firing, similar to cholinergic interneurons. As in cholinergic interneurons, these firing patterns arise from interactions between multiple intrinsic oscillatory mechanisms, but the mechanisms responsible differ. Both neurons maintain tonic firing because of persistent sodium currents, but the mechanisms of the subthreshold oscillations responsible for irregular firing are different. In LTS interneurons they rely on depolarization-activated noninactivating calcium currents, whereas those in cholinergic interneurons arise from a hyperpolarization-activated potassium conductance. Sustained membrane hyperpolarizations induce a bursting pattern in LTS interneurons, probably by recruiting a low-threshold, inactivating calcium conductance and by moving the membrane potential out of the activation range of the oscillatory mechanisms responsible for single spiking, in contrast to the bursting driven by noninactivating currents in cholinergic interneurons. The complex intrinsic firing patterns of LTS interneurons may subserve differential release of classic and peptide neurotransmitters as well as nitric oxide.

Cell-type-specific resonances shape the responses of striatal neurons to synaptic input

“…All cells also showed the characteristic membrane potential and spiking responses to depolarizing and hyperpolarizing current pulses associated with this neuron type (Fig. 5B), consisting of a moderate depolarizing sag when hyperpolarized by negative current pulses and a characteristic rebound burst when hyperpolarizing pulses were terminated (e.g., Kawaguchi 1993;Ibáñez-Sandoval et al 2011;Beatty et al 2012). All cells identified as LTS cells showed spontaneous firing during perforated patch recordings, with firing rates from 1.8 to 18.6 spikes/s (mean: 9.0 Ϯ 4.0).…”

“…Perhaps the oscillations and resonance share a similar mechanism. The oscillations persist after blockade of sodium channels but are sensitive to blockade of calcium channels (Beatty et al 2012).…”

“…We measured membrane resonance at Ϫ80 mV (outside the range of the normal membrane potential trajectory) or Ϫ50 mV (within the range of interspike membrane potentials). LTS neurons show membrane potential oscillations at potentials positive to Ϫ40 mV (Beatty et al 2012), so it was important to test for resonance at depolarized potentials. In most neurons, action currents interrupted our measurements at membrane potentials too near the action potential threshold, but in a few cells we were able to hold the cells as depolarized as Ϫ30 mV long enough to complete the test.…”

“…We have previously shown that the striatal fast-spiking interneuron exhibits a minimum repetitive firing frequency in the gamma-frequency range, which should make it more sensitive to fluctuations in synaptic current at this frequency (Sciamanna and Wilson 2011). Another striatal interneuron, the giant cholinergic interneuron, exhibits intrinsic low-frequency oscillations (Wilson 2005), and a third, the low-threshold spiking interneuron has calcium-dependent oscillations at depolarized potentials (Beatty et al 2012).…”

Social Interaction and Cocaine Conditioning in Mice Increase Spontaneous Spike Frequency in the Nucleus Accumbens or Septal Nuclei as Revealed by Multielectrode Array Recordings

“…Five different interneuron types account for a few percent of the whole neuronal population [21]. Of those, cholinergic interneurons and NPY + GABAergic interneurons show regular electrical activity in vitro, which is independent of synaptic input [18,22,23,24]. Thus, it seems likely that the spontaneously active neurons we recorded in these regions are these different types of interneurons.…”