Indeed, the change in spike transmission probability between probe sessions correlated with the number of pairing events during learning, independent of whether the interneuron Fulvestrant molecular weight fired before or after the pyramidal cell ( Figure 7A; −20 ms: r = 0.394; +20 ms: r = 0.398; all p’s < 0.00001). This was the case for both the nInt (r = 0.222, p = 0.026) and the pInt (r = 0.419; p = 0.013). Moreover, the number of pairing events was also associated with a change in transmission latency: the more often pyramidal cells were paired with an interneurons spike during learning, the shorter the subsequent pyramidal cell-interneuron

connection delay ( Figure 7B; –20 ms: r = 0.432; +20 ms: r = 0.442; all p’s < 0.00001). We showed above that the number of Talazoparib cost pairing events predicted the change of pyramidal cell-interneuron connection changes. However, the number of pairings with pyramidal cells during learning does not guarantee that specific associations are made with newly formed assemblies, since old assemblies are also intermittently present during learning trials. Because the reorganization of place cells were focused on newly learned goal locations, pairing events at these locations may have been

more efficient at shaping the connections. Thus, we determined whether neuronal pairing at goal locations facilitated the strengthening or weakening of synaptic connections. Spike-pairing events (±20 ms time difference) occurred both inside and outside the goal areas (Figure 7C)

although more occurred outside than inside (inside = 133.8 ± 16.7, outside = 850.4 ± 65.1, p < 0.00001, t test). Nevertheless, the change in transmission probability was better predicted by pairings occurring inside goal areas (Figure 7D). Consistent with this, the strengthening of the pyramidal cell-interneuron connection was greater when the pre-synaptic pyramidal cell exhibited goal-centric firing (Figure 7E; goal-centric cells: r = 0.581; non-goal-centric cells: r = 0.232; Z = 2.163, Fisher z-test), as indicated by a steeper slope of the regression line (goal-centric cells > non-goal-centric cells, p = 0.010). Together these results suggest that the coincident firing of the pyramidal cells and their target interneurons governed changes of their connection strength and that such pairing was more effective in influencing Edoxaban connection changes when it took place at the newly learned goal locations. In vitro experiments have suggested that some postsynaptic interneurons need to be depolarized to observe synaptic changes, suggesting that the ongoing interneuron excitation state can influence pyramidal cell-interneuron connection changes. Spike trains of interneurons were convolved with a one-dimensional Gaussian kernel with a width parameter σ of 20 ms to provide a continuous measure of their spike density during learning (Figure 8A; Kruskal et al., 2007).