Dataset Information

Striatal Low-Threshold Spiking Interneurons Regulate Goal-Directed Learning.

ABSTRACT: The dorsomedial striatum (DMS) is critically involved in motor control and reward processing, but the specific neural circuit mediators are poorly understood. Recent evidence highlights the extensive connectivity of low-threshold spiking interneurons (LTSIs) within local striatal circuitry; however, the in vivo function of LTSIs remains largely unexplored. We employed fiber photometry to assess LTSI calcium activity in a range of DMS-mediated behaviors, uncovering specific reward-related activity that is down-modulated during goal-directed learning. Using two mechanistically distinct manipulations, we demonstrated that this down-modulation of LTSI activity is critical for acquisition of novel contingencies, but not for their modification. In contrast, continued LTSI activation slowed instrumental learning. Similar manipulations of fast-spiking interneurons did not reproduce these effects, implying a specific function of LTSIs. Finally, we revealed a role for the γ-aminobutyric acid (GABA)ergic functions of LTSIs in learning. Together, our data provide new insights into this striatal interneuron subclass as important gatekeepers of goal-directed learning.

SUBMITTER: Holly EN

PROVIDER: S-EPMC8487455 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Publications

Striatal Low-Threshold Spiking Interneurons Regulate Goal-Directed Learning.

Holly Elizabeth N EN Davatolhagh M Felicia MF Choi Kyuhyun K Alabi Opeyemi O OO Vargas Cifuentes Luigim L Fuccillo Marc V MV

Neuron 20190513 1

The dorsomedial striatum (DMS) is critically involved in motor control and reward processing, but the specific neural circuit mediators are poorly understood. Recent evidence highlights the extensive connectivity of low-threshold spiking interneurons (LTSIs) within local striatal circuitry; however, the in vivo function of LTSIs remains largely unexplored. We employed fiber photometry to assess LTSI calcium activity in a range of DMS-mediated behaviors, uncovering specific reward-related activit ...[more]

PMID: 31097361

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Project description:Striatal fast-spiking interneurons (FSIs) fire in variable-length runs of action potentials at 20-200 spikes/s separated by pauses. In vivo, or with fluctuating applied current, both runs and pauses become briefer and more variable. During runs, spikes are entrained specifically to gamma-frequency components of the input fluctuations. We stimulated parvalbumin-expressing striatal FSIs in mouse brain slices with broadband noise currents added to direct current steps and measured spike entrainment across all frequencies. As the constant current level was increased, FSIs produced longer runs and showed sharper frequency tuning, with best entrainment at the stimulus frequency matching their intrarun firing rate. We separated the contributions of previous spikes from that of the fluctuating stimulus, revealing a strong contribution of previous action potentials to gamma-frequency entrainment. In contrast, after subtraction of the effect inherited from the previous spike, the remaining stimulus contribution to spike generation was less sharply tuned, showing a larger contribution of lower frequencies. The frequency specificity of entrainment within a run was reproduced with a phase resetting model based on experimentally measured phase resetting curves of the same FSIs. In the model, broadly tuned phase entrainment for the first spike in a run evolved into sharply tuned gamma entrainment over the next few spikes. The data and modeling results indicate that for FSIs firing in brief runs and pauses firing within runs is entrained by gamma-frequency components of the input, whereas the onset timing of runs may be sensitive to a wider range of stimulus frequency components.NEW & NOTEWORTHY Specific types of neurons entrain their spikes to particular oscillation frequencies in their synaptic input. This entrainment is commonly understood in terms of the subthreshold voltage response, but how this translates to spiking is not clear. We show that in striatal fast-spiking interneurons, entrainment to gamma-frequency input depends on rhythmic spike runs and is explained by the phase resetting curve, whereas run initiation can be triggered by a broad range of input frequencies.

Dataset Information

Striatal Low-Threshold Spiking Interneurons Regulate Goal-Directed Learning.

Publications

Striatal Low-Threshold Spiking Interneurons Regulate Goal-Directed Learning.

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