Spike Entrainment and Synaptic Output of Striatal Low-threshold Spike Interneurons

As the input elements of the basal ganglia, neurons in the striatum are tasked with extracting the signals from their afferent inputs and transmitting them to downstream targets. Signals arriving in the striatum get modified by local circuits that are comprised of multiple cell- types, each with their own properties. We studied the frequency preference of striatal low- threshold spike (LTS) interneurons and spiny projection (SP) neurons individually and as a microcircuit. Using a combination of electrophysiology and computational modeling, we found that given an input with identical statistics and frequency content, LTS cells are strongly entrained by a broad range of frequencies, whereas SP neurons are more narrowly tuned around their firing rate. Systematic manipulation of each cell-type's average phase resetting curve (PRC) showed that the differences in entrainment could be explained by the differences in the frequency content embedded within their PRCs. Because LTS cells synapse onto SP neurons, we further explored our findings by using optogenetics to entrain multiple LTS cells simultaneously to study the propagation of signals across a synapse. We found that oscillatory signals could indeed propagate across the LTS to SPN synapse and that they were large enough to affect the entrained spiking of spiny neurons. Using a phase model of frequency-modulated synaptic inhibition, we found that experimentally measured GABAergic currents affected spike timing in a frequency- dependent manner. Our results suggest that depending on the state of the microcircuit, frequency modulated inhibitory input could act constructively or destructively with spiny neuron spiking.