RT Journal Article SR Electronic T1 Intra-dorsal striatal acetylcholine M1 but not dopaminergic D1 or glutamatergic NMDA receptor antagonists inhibit the consolidation of duration memory in interval timing JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.05.24.445416 DO 10.1101/2021.05.24.445416 A1 Masahiko Nishioka A1 Taisuke Kamada A1 Atsushi Nakata A1 Naoko Shiokawa A1 Aoi Kinoshita A1 Toshimichi Hata YR 2021 UL http://biorxiv.org/content/early/2021/05/25/2021.05.24.445416.abstract AB The striatal beat frequency (SBF) model assumes that striatal medium spiny neurons encode duration via synaptic plasticity. Muscarinic 1 (M1) cholinergic receptors, as well as dopamine and glutamate receptors, are important for neural plasticity in the dorsal striatum. Therefore, we investigated the effect of inhibiting these receptors on the formation of duration memory. After sufficient training in a Peak interval (PI)-20 s procedure, rats were given a single or mixed infusion of a selective antagonist for the dopamine D1 receptor (SCH23390, 0.5 µg per side), the NMDA-type glutamate receptor (D-AP5, 3 µg), or the M1 receptor (pirenzepine, 10 µg) bilaterally in the dorsal striatum, immediately before starting a PI 40 s session (shift session). On the next day, the rats were tested for new duration memory (40 s) in a session in which no lever presses were reinforced (probe session). In the shift session, performance was tie, irrespective of the drug injected. However, in the probe session, the mean peak time (an index of duration memory) of the M1 + NMDA co-blockade group, but not of the D1 + NMDA co-blockade group, was lower than that of the control group (Exp. 1 and 2). In Exp. 3, the effect of the co-blockade of M1 and NMDA receptors was replicated. Moreover, sole blockade of M1 receptors induced the same effect as M1 and NMDA blockade. These results suggest that in the dorsal striatum, the M1 receptor, but not the D1 or NMDA receptors, are involved in the consolidation of duration memory.Highlights D1 and NMDA receptors are not involved in the formation of duration memory. M1 receptors are involved in the consolidation of duration memory.These findings narrow the candidates for the receptor types inducing neuronal plasticity underlying the formation of duration memory in the SBF model.Competing Interest StatementThe authors have declared no competing interest.SBF(Striatal Beat Frequency)DS(dorsal striatum)MSNs(medium spiny neurons)HFS(high frequency stimulus)ERK(extracellular signal-regulated kinase)Arc(activity-regulated cytoskeletal-associated protein kinase)PI(peak interval)DI(discrimination index)Pir(pirenzepine)PPT(pedunculopontine)LDT(laterodorsal tegmental nuclei).