033 Hz, resulted in an immediate change of the size of the synaptic

response. This effect was temporally dependent in that by varying the time interval and order of the stimulations, the pairing resulted in various Akt activation forms of synaptic plasticity of the SC-CA1 synaptic transmission (Figures 1C and 1D). When pairing SO stimulation 100 ms before the SC stimulation, robust LTP of the EPSC amplitude was induced; intervals of 200 and 50 ms were less effective and only produced a short-term potentiation (STP; Figures 1C and 1D). When the interval was shortened to 10 ms, short-term depression (STD) was induced with a less significant effect at a duration of 20 ms. Concurrent stimulation of the SO and SC did not induce any changes in the synaptic response. However, when the SO stimulation was given after the SC stimulation, LTP was induced at the 10 ms time interval,

with a slight potentiation at 20 ms and no effect at 50, 100, or 200 ms intervals (Figures 1C and 1D). Interestingly, whereas only five pairings were almost as effective as ten when using ±10 ms intervals (SO before or after SC), five pairings induced only STP instead of LTP when pairing SO 100 ms before SC (Figures S1E–S1H). The induction of different forms of plasticity stresses the importance of the timing of cholinergic inputs and local synaptic activity in inducing this type of synaptic plasticity. This plasticity depends on both the BKM120 purchase timing of the cholinergic input and the activity of local hippocampal synapses receiving the input. Thus, one cholinergic input may result in different types of plasticity at different synapses, ADP ribosylation factor depending on the local glutamatergic activity in each spine. Thus, this timing- and context-dependent mechanism provides not only temporal but also spatial precision. To investigate which AChRs might be involved in mediating these forms of plasticity, bath application of cholinergic receptor antagonists was used during the pairing protocol (Figures

2A–2D); MLA and DHβE were used to test for the α7 and non-α7 nAChRs, respectively, and atropine was used to test for the mAChR (Figures 2E–2H). The LTP induced by the preceding SO stimulation (100 ms) was completely blocked by MLA (10 nM), whereas DHβE (1 μM) and atropine (5 μM) were ineffective (Figure 2A). Similarly, the induction of STD by SO 10 ms before SC was also blocked by MLA, with DHβE and atropine also having no effect (Figure 2B). Therefore, induction of either LTP or STD with prior SO stimulation was due to activation of the α7 nAChR. In contrast the LTP induced when the SO stimulation occurred after (10 ms) SC stimulation was insensitive to blockade of nAChRs but was blocked by the mAChR antagonist atropine ( Figure 2C), indicating that mAChRs mediated this form of plasticity.