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Neurosci."],"accepted":{"date-parts":[[2026,1,28]]},"published-print":{"date-parts":[[2026,3,4]]},"abstract":"<jats:p>Fast-spiking, nonadaptive inhibitory neurons in the thalamic reticular nucleus (TRN) critically gate the reciprocal communication between the thalamus and the cortex. Parvalbumin (PV) neurons express high levels of PV, the sole role of which appears to be calcium buffering. The significance of the PV protein\u2014and its related high calcium-buffering capacity\u2014under pathological conditions, especially in various neuropsychiatric disorders, is underappreciated. Deficiency of SHANK3, an important neuronal protein containing ankyrin, SH3, and PDZ, three canonical domains for protein recognition, causes behavioral changes relevant to autism spectrum disorders (ASDs). Here we report TRN PV neurons of Shank3\u2212\/\u2212 (exon 4\u201322 deletion) mice of either sex exhibit pronounced increases in burst firing occurrence, decreased tonic firing frequency, and faster dendritic calcium transient decay. We pinpointed reduced PV expression as the culprit and used the added buffer approach to confirm the decrease in calcium-buffering capacity in mutant neurons. Conversely, supplementing Shank3\u2212\/\u2212 PV neurons with extra EGTA reverses the abnormal action potential (AP) firing. In addition, the PV neurons from HCN2\u2212\/\u2212 mice exhibit consistent changes in neuronal excitability, PV expression, and calcium signaling. Together with the study of dopaminergic (DA) neurons in the ventral tegmental area (VTA), these results uncover reduced PV expression, calcium-buffering capacity, and altered neuronal excitability in Shank3\u2212\/\u2212 and HCN2\u2212\/\u2212 mice. This pathway, downstream of Shank3 deficiency and HCN channelopathy, may form an important pathological basis not only for ASD but also other neuropsychiatric disorders.<\/jats:p>","DOI":"10.1523\/jneurosci.1202-25.2026","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T18:50:16Z","timestamp":1770144616000},"page":"e1202252026","update-policy":"https:\/\/doi.org\/10.1523\/jneurosci.crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Abnormal Neuronal Excitability and Reduced Parvalbumin Expression in Shank3-Deficient Parvalbumin Neurons of the Thalamic Reticular 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