Qinlin Liu

Striatal output is dynamically modulated by cholinergic interneurons (CINs), the primary source of acetylcholine in the striatum. CINs have been classically viewed as a random and homogeneous population, but recent evidence suggests heterogeneity in their anatomical and functional organization. Here, using systematic mapping and quantitative spatial analyses, we found that—contrary to current dogma—CINs exhibited striking enrichment and nonrandom clustering in the striosome compartment, particularly in the lateral striatum. Similar analyses carried out for parvalbumin- and somatostatin-expressing interneurons revealed that compartmental organization is interneuron specific. The strong “striosome preference” exhibited by CINs was confined within striosome borders, not extending to the surrounding matrix. We further found that striosome and matrix CINs differed in their expression levels of phospho-S6 ribosomal protein-Ser240/244 and choline acetyltransferase, suggesting functional differences, and clustered CINs differed from unclustered CINs in their intrinsic membrane properties. Finally, CINs expressing Lhx6, which defines a distinct γ-aminobutyric acid (GABA) coreleasing population, were notably absent from regions where highly clustered striosomal CINs appeared. Collectively, our findings uncover important dimensions of CIN organization, suggesting that modulation of regional and compartmental striatal output may depend upon the spatial–functional heterogeneity of CINs.

Purpose: To explore changes of depression, anxiety and sleep disturbance in patients with episodic cluster headache inside and outside the attack period and assess the therapy to improve the treatment. Patients and Methods: We prospectively recruited 396 patients from 11 specialized headache outpatients and analyzed their headache characteristics, Hospital Anxiety Depression Scale scores, Pittsburgh sleep quality index scores, and the usage of psychiatric medications during as well as 1 month after the attack period. Results: A total of 220 patients completed the follow-up, 52.73% of whom had anxiety, 47.27% had depression and 49.09% had sleep disturbance inside the attack period. At follow-up, the percentage of these patients significantly decreased to 16.36%, 21.82% and 14.55% in the remission period, respectively (p < 0.05). Antidepressants and mood stabilizers were prescribed to 58.18% of the patients. However, both of the changes of Hospital Anxiety Depression Scale scores after the end of the attack period for anxiety (3.52± 2.91 vs 3.32± 3.09, p =0.61) and depression (3.41± 3.33 vs 2.90± 3.58, P =0.28) were comparable in patients with and without taking these medications. Nocturnal onset of headache was positively correlated with Pittsburgh score (OR=8.71), anxiety (OR=2.33) and depression scores (OR=3.56) (p < 0.05). Conclusion: Depression, anxiety and sleep disturbance were significantly alleviated after the attack period. However, psychiatric medications showed limited effect on depression and anxiety. Additionally, the nocturnal attack may cause anxiety and depression in episodic cluster headache.