Functional autapses form in striatal parvalbumin interneurons but not medium spiny neurons

Abstract Autapses (or self-synapses) selectively form in specific cell types in many brain regions including the neocortex and the hippocampus, where they provide feedback control over self-spiking activities. Previous morphological studies also found putative autapses in medium spiny neurons (MSNs) of the striatum. However, it remains unclear whether striatal neurons indeed form physiologically functional autapses. We performed whole-cell recordings from striatal neurons in acute mouse brain slices, and identify autaptic neurons by the occurrence of prolonged asynchronous release (AR) of neurotransmitter after high-frequency burst of action potentials (APs) in the same cell. To our surprise, we found no autaptic release in all recorded MSNs after the AP burst, even in the presence of Sr 2+ that should desynchronize and thus prolong synaptic vesicle release. In sharp contrast, we observed robust autaptic AR events in half of the recorded parvalbumin (PV)-positive neurons. Autaptic responses in PV cells were mediated by GABA A receptors, and the AR strength was dependent on the frequency and the number of APs during the burst. Further simulation results show that autapses regulate burst spiking in PV cells by providing self-inhibition and thus shape network oscillation at certain frequencies. Together, we reveal that, distinct from MSNs, striatal PV neurons form functional autapses, activation of which would regulate self-activities in PV cells, and thereby shape MSN firing and network oscillations. Author summary Synapses, which usually occur between two neurons, are key structures for signal communication in the nervous system. However, some types of neurons form autapses, where a neuron synapses onto itself. Autaptic transmission provides feedback signal regulating self-spiking activities. Neuronal and network activities in the striatum play critical roles in motor control and other brain functions. Previous studies suggest formation of autapses in striatal principal MSNs, but it remains unclear whether striatal neurons form functional autapses. We performed direct recordings from striatal neurons and examined the occurrence of autaptic transmission in acute brain slices. Surprisingly, we did not detect any autaptic responses in MSNs. A large proportion of striatal PV neurons, however, produced robust autaptic GABA release upon high-frequency stimulation, indicating selective formation of autapses in striatal PV cells. Our computation simulations suggest that autapses provide self-inhibition in PV cells and thereby shape activities in MSNs and striatal network, particularly when PV cells discharge at high frequencies corresponding to a high dopamine state. Together, our findings indicate that PV cells, but not MSNs, in the striatum form physiologically functional autapses. Autapses in PV cells could be essential circuit elements in the striatum and contribute to striatal functions, such as motor control.