Optogenetic stimulation reveals distinct modulatory properties of thalamostriatal vs corticostriatal glutamatergic inputs to fast-spiking interneurons.

Giuseppe Sciamanna,Paola Bonsi,Giulia Ponterio,Georgia Mandolesi,Antonio Pisani

doi:10.1038/srep16742

Giuseppe Sciamanna, Paola Bonsi + Show 3 more

Open Access

https://doi.org/10.1038/srep16742

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Abstract

Parvalbumin-containing fast-spiking interneurons (FSIs) exert a powerful feed-forward GABAergic inhibition on striatal medium spiny neurons (MSNs), playing a critical role in timing striatal output. However, how glutamatergic inputs modulate their firing activity is still unexplored. Here, by means of a combined optogenetic and electrophysiological approach, we provide evidence for a differential modulation of cortico- vs thalamo-striatal synaptic inputs to FSIs in transgenic mice carrying light-gated ion channels channelrhodopsin-2 (ChR2) in glutamatergic fibers. Corticostriatal synapses show a postsynaptic facilitation, whereas thalamostriatal synapses present a postsynaptic depression. Moreover, thalamostriatal synapses exhibit more prominent AMPA-mediated currents than corticostriatal synapses, and an increased release probability. Furthermore, during current-evoked firing activity, simultaneous corticostriatal stimulation increases bursting activity. Conversely, thalamostriatal fiber activation shifts the canonical burst-pause activity to a more prolonged, regular firing pattern. However, this change in firing pattern was accompanied by a significant rise in the frequency of membrane potential oscillations. Notably, the responses to thalamic stimulation were fully abolished by blocking metabotropic glutamate 1 (mGlu1) receptor subtype, whereas both acetylcholine and dopamine receptor antagonists were ineffective. Our findings demonstrate that cortical and thalamic glutamatergic input differently modulate FSIs firing activity through specific intrinsic and synaptic properties, exerting a powerful influence on striatal outputs.

Highlights

Parvalbumin-containing fast-spiking interneurons (FSIs) exert a powerful feed-forward GABAergic inhibition on striatal medium spiny neurons (MSNs), playing a critical role in timing striatal output
excitatory post-synaptic current (EPSC) elicited by electrical stimulation at both corticostriatal and thalamostriatal fibers had a higher coefficient of variation (CV) value compared to stimulation triggered by light pulse (Fig. 1h)
The main findings of the present study show that thalamostriatal afferents differently modulate FSIs excitability compared to glutamatergic cortical inputs

Summary

Introduction

Parvalbumin-containing fast-spiking interneurons (FSIs) exert a powerful feed-forward GABAergic inhibition on striatal medium spiny neurons (MSNs), playing a critical role in timing striatal output. Parvalbumin-containing fast-spiking interneurons (FSIs) receive inputs from cerebral cortex and from intralaminar thalamic nuclei[10,11] Despite such evidence, the synaptic properties of these glutamatergic inputs to FSIs have not been characterized yet. FSIs show peculiar firing properties[13,14]: with current injection they exhibit an intermittent firing pattern consisting of periods of high frequency spike trains abruptly interrupted by periods of quiescence and subthreshold oscillation[15,16] The mechanisms underlying such peculiar pattern is not well understood, previous data demonstrated that membrane oscillations can trigger the intermittent spike bursts[15], and that intermittent pattern requires the presence of the low-threshold slowly inactivating Kv1 current[16]. We demonstrate that excitatory synapses originating from cortex and thalamus differently modulate FSIs excitability

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