| First Author | Holly EN | Year | 2019 |
| Journal | Neuron | Volume | 103 |
| Issue | 1 | Pages | 92-101.e6 |
| PubMed ID | 31097361 | Mgi Jnum | J:279569 |
| Mgi Id | MGI:6355576 | Doi | 10.1016/j.neuron.2019.04.016 |
| Citation | Holly EN, et al. (2019) Striatal Low-Threshold Spiking Interneurons Regulate Goal-Directed Learning. Neuron 103(1):92-101.e6 |
| abstractText | 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 gamma-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. |
