over 3 min) for 20 tests. acquired memories. It is believed that experience-dependent changes in synaptic strength are crucial for information storage in the mind1,2. However, it remains unclear whether and how synaptic plasticity induced by past experiences are managed in the face of new experiences1C3. To address this question, we examined the generation of dendritic Ca2+ spikes and their effect on synaptic plasticity in the primary engine cortex of mice carrying out different engine learning jobs. Dendritic Ca2+ spikes result in large Ca2+ influx into dendrites4C8, and have been linked to activity-dependent raises or decreases of synaptic strength in brain slices9C14. Recent studies have shown that NMDA (= 9 mice, combined = 24) during FWR. Red trace represents the average. f, The number of Ca2+ transients improved 7-collapse during FWR or BWR relative to resting (= 2.6 10?7, paired = 321), BWR (= 261) and FWR with community MK801 (= 34) over 2.5 min. h, Distribution of AWS maximum Ca2+ spike amplitudes recognized with GCaMP6s and GCaMP2.2c Acetohydroxamic acid during FWR with or without MK801 (= 141, 213 and 31, respectively; 0.0001, MannCWhitney test). = 616 for two jobs; = 450 for four jobs). j, 53% of apical trunks exhibited Ca2+ transients in response to several jobs (= 257). k, Sibling branches exhibited non-overlapping FWR- and BWR-induced Ca2+ spikes. l, Two-dimensional projection of multiple sibling branches. Green arrowhead marks the trunk. Six regions of interests (ROIs) related to different branches were analysed over five tests of FWR and BWR. m, The percentage of sibling branches with overlapping FWR/BWR-induced Ca2+ spikes at two cortical depths below the Acetohydroxamic acid pia. Data are mean s.e.m. *** 0.001. Observe Methods for statistical details. When mice underwent ahead running (FWR) and then backward operating (BWR) (five 30-s tests for each direction), of the tuft branches that spiked and were located within 100 m below the pial surface, ~95% exhibited Ca2+ spikes during either FWR or BWR, while only ~5% showed Ca2+ spikes during both operating jobs (Fig. 1i). Furthermore, in mice qualified to run in four directions, only ~10% of those tuft branches exhibited Ca2+ spikes in response to two or more jobs (Fig. 1i). Therefore, different running jobs induce Ca2+ spikes on different Acetohydroxamic acid tuft branches with little overlap. In contrast to non-overlapping Ca2+ spikes on distal tuft branches, we observed considerable overlap of Ca2+ activities in apical dendritic trunks (nexus, near the foundation of tuft branches) and L5 somata when mice were subjected to two or four direction operating (Fig. 1a, j, l and Extended Data Fig. 3aCe). This observation suggests that different engine jobs induce Ca2+ spikes on independent tuft branches of the same L5 pyramidal neurons. Indeed, out of 33 pairs of sibling branches located within 100 m below the pial surface, only 2 pairs showed FWR- and BWR-induced Ca2+ spikes on the same branches, whereas the remaining 31 pairs exhibited no such overlap (Fig. 1k, m and Extended Data Fig. 3h). As these higher-order tuft branches converge towards nexus, a larger overlap of FWR-and BWR-induced Ca2+ spikes was observed on sibling branches located 100C200 m from your pial surface (Fig. 1l, m and Extended Data Fig. 3f, g, i, j). At this cortical depth, ~16% of Ca2+ spikes (48 out of 294 spikes) occurred simultaneously in all branches (global) of the same neuron in response to FWR or BWR (Prolonged Data Fig. 3k). Notably, when tuft branches from an individual neuron were cut having a two-photon laser, running-induced Ca2+ activity in the trunk was significantly reduced (Extended Data Fig. 4). Collectively, these findings indicate that different engine tasks result in Ca2+ spikes in mainly non-overlapping distal apical tuft branches of the same L5 pyramidal neurons (Fig. 1m, Extended Data Fig. 3j and Supplementary Info). They also suggest that Ca2+ spikes generated in individual tuft branches propagate along dendrites and contribute to the activity in apical trunks and somata. Spines active during BSDCS are potentiated Dendritic Ca2+ spikes have been shown to result in long-term synaptic potentiation or major depression in brain slices9C14. To investigate the effect of Ca2+ spikes on synaptic plasticity 0.001).Notably, after Ca2+ spikes, these active spines exhibited a significant increase in the peak amplitude of Ca2+ transients (Fig. 2aCc and Extended Data Fig. 5hCj, mCo; 74.7 7.3% for FWR (= 80) and 52.7 10.9% for BWR (= 18); 0.001). By contrast, no significant potentiation.