However, when mice were subjected to BWR after FWR and their performances in FWR were tested again, SST-deleted mice exhibited a significant reduction in the stride length and an increase in the width between forelimbs when compared to control mice (Fig

However, when mice were subjected to BWR after FWR and their performances in FWR were tested again, SST-deleted mice exhibited a significant reduction in the stride length and an increase in the width between forelimbs when compared to control mice (Fig. experiences. One remarkable feature of the brain is to encode and store new information continuously without disrupting previously acquired memories. It is believed that experience-dependent changes in synaptic strength are crucial for information storage in the brain1,2. However, it remains unclear whether and how synaptic plasticity induced by past experiences are maintained 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 motor cortex of mice performing different motor learning tasks. Dendritic Ca2+ spikes trigger large Ca2+ influx into dendrites4C8, and have been linked to activity-dependent increases or decreases of synaptic strength in brain slices9C14. Recent studies have shown that NMDA (= 9 mice, paired = 24) during FWR. Red trace represents the average. f, The number of Ca2+ transients increased 7-fold during FWR or BWR relative to resting (= 2.6 10?7, paired = 321), BWR (= 261) and FWR with local MK801 (= 34) over 2.5 min. h, Distribution of peak DRI-C21045 Ca2+ spike amplitudes detected with GCaMP6s and GCaMP2.2c during FWR with or without MK801 (= 141, 213 and 31, respectively; 0.0001, MannCWhitney test). = 616 for two tasks; = 450 for four tasks). j, 53% of apical trunks exhibited Ca2+ transients in response to several tasks (= 257). k, Sibling branches Rabbit Polyclonal to Retinoic Acid Receptor beta 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) corresponding to different branches were analysed over five trials of FWR and BWR. m, The percentage of sibling branches with overlapping FWR/BWR-induced Ca2+ spikes at two cortical depths below the pia. Data are mean s.e.m. *** 0.001. See Methods for statistical details. When mice underwent forward running (FWR) and then backward running (BWR) (five 30-s trials 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 running tasks (Fig. 1i). Furthermore, in mice trained to run in four directions, only ~10% of those tuft branches exhibited Ca2+ spikes in response to two or more tasks (Fig. 1i). Thus, different running tasks induce Ca2+ spikes on different tuft branches with little overlap. In contrast to non-overlapping Ca2+ spikes on distal tuft branches, we observed substantial overlap of Ca2+ activities in apical dendritic trunks (nexus, near the base of tuft branches) and L5 somata when mice were subjected to two or four direction running (Fig. 1a, j, l and Extended Data Fig. 3aCe). This observation suggests that different motor tasks induce Ca2+ spikes on separate 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 the nexus, a larger overlap of FWR-and BWR-induced Ca2+ spikes was observed on sibling branches located 100C200 m from the 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 (Extended Data Fig. 3k). Notably, when tuft branches from an individual neuron were cut with a two-photon laser, running-induced Ca2+ activity in the trunk was significantly reduced (Extended Data Fig. 4). Together, these findings indicate.performed experiments and analysed the data with the help from W.-B.G. memories. It is believed that experience-dependent changes in synaptic strength are crucial for information storage in the brain1,2. However, it remains unclear whether and how synaptic plasticity induced by past experiences are maintained in the face of new experiences1C3. To address this question, we examined the generation of dendritic Ca2+ spikes and DRI-C21045 their effect on synaptic plasticity in the primary motor cortex of mice performing different motor learning tasks. Dendritic Ca2+ spikes trigger large Ca2+ influx into dendrites4C8, and have been linked to activity-dependent increases or DRI-C21045 decreases of synaptic strength in brain slices9C14. Recent studies have shown that NMDA (= 9 mice, paired = 24) during FWR. Red trace represents the average. f, The number of Ca2+ transients increased 7-fold during FWR or BWR relative to resting (= 2.6 10?7, paired = 321), BWR (= 261) and FWR with local MK801 (= 34) over 2.5 min. h, Distribution of peak Ca2+ spike amplitudes detected with GCaMP6s and GCaMP2.2c during FWR with or without MK801 (= 141, 213 and 31, respectively; 0.0001, MannCWhitney test). = 616 for two tasks; = 450 for four tasks). j, 53% of apical trunks exhibited Ca2+ transients in response to several tasks (= 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) corresponding to different branches were analysed over five trials of FWR and BWR. m, The percentage of sibling branches with overlapping FWR/BWR-induced Ca2+ spikes at two cortical depths below the pia. Data are mean s.e.m. *** 0.001. See Methods for statistical details. When mice underwent forward running (FWR) and then backward running (BWR) (five 30-s trials 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 running tasks (Fig. 1i). Furthermore, in mice trained to run in four directions, only ~10% of those tuft branches exhibited Ca2+ spikes in response to two or more tasks (Fig. 1i). Thus, different running tasks induce Ca2+ spikes on different tuft branches with little overlap. In contrast to non-overlapping Ca2+ spikes on distal tuft branches, we observed substantial overlap of Ca2+ activities in apical dendritic trunks (nexus, near the base of tuft branches) and L5 somata when mice were subjected to two or four direction running (Fig. 1a, j, l and Extended Data Fig. 3aCe). This observation suggests that different motor tasks induce Ca2+ spikes on separate 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 the nexus, a larger overlap of FWR-and BWR-induced Ca2+ spikes was observed on sibling branches located 100C200 m from the 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 (Extended Data Fig. 3k). Notably, when tuft branches from an individual neuron were cut with a two-photon laser, running-induced Ca2+ activity in the trunk was significantly reduced (Extended Data Fig. 4). Together, these findings indicate that different motor tasks trigger Ca2+ spikes in largely non-overlapping distal apical tuft branches of the same L5 pyramidal neurons (Fig. 1m, Extended Data Fig. 3j and Supplementary Information). 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 trigger long-term synaptic potentiation or depression in brain slices9C14. To.