P.S.B., A.G., I.V., and D.S. wrote the paper. “
“The output of principal neurons is driven by excitatory input from diverse brain regions while being constrained by local inhibition. Activity-dependent forms of plasticity at excitatory and inhibitory synapses, such as long-term potentiation (LTP) and depression (LTD), may provide cellular bases

for memory storage Bleomycin purchase within a circuit (Kullmann et al., 2012, Malenka and Bear, 2004 and Mayford et al., 2012). Most studies of LTP and LTD have focused on homosynaptic forms of plasticity at excitatory synapses that represent unsupervised synaptic learning rules where activity in a single synaptic pathway alters its own efficacy. Less is known about how convergent inputs from distinct brain regions generate heterosynaptic forms of plasticity in which activity NVP-BGJ398 datasheet in one pathway alters information flow through a second path. Such supervised learning rules are of great theoretical interest as they provide a rich substrate for circuits to perform a wide range of mnemonic computations (Abbott and Regehr, 2004 and Spruston, 2008). Here we define

how a physiologically relevant, temporally precise pattern of activation of distinct cortical and hippocampal inputs to CA1 pyramidal neurons (PNs) implements a heterosynaptic form of plasticity to shape information transfer through the hippocampal macrocircuit by regulating the output of a local inhibitory microcircuit. In the cortico-hippocampal excitatory circuit, inputs carrying information from distinct layers of the entorhinal cortex (EC) converge on CA1 PNs through two main pathways (Kajiwara et al., 2008). CA1 PNs are excited directly by LIII EC neurons Oxygenase through perforant path (PP) synapses on distal CA1 dendrites

in stratum lacunosum moleculare (SLM) and indirectly by LII EC neurons through the trisynaptic path (EC LII→DG→CA3→CA1), in which CA3 Schaffer collaterals (SC) ultimately form synapses on proximal CA1 dendrites in stratum radiatum (SR) (Amaral and Witter, 1989). This circuit architecture adds a delay line for signals routed through the trisynaptic versus the monosynaptic path (Yeckel and Berger, 1990). Interestingly, although the direct EC inputs only weakly excite CA1 PNs (Jarsky et al., 2005), this sensory information regulates the propagation of signals through the hippocampal trisynaptic loop (Dudman et al., 2007, Golding et al., 2002, Han and Heinemann, 2013, Levy et al., 1998, Remondes and Schuman, 2002, Takahashi and Magee, 2009 and Wöhrl et al., 2007) and is crucial for spatial (Remondes and Schuman, 2004 and Steffenach et al., 2005) and temporal (Suh et al., 2011) memory. One way that the weak PP inputs may influence CA1 output is by providing instructive signals for a powerful form of heterosynaptic plasticity at the SC-CA1 synapses termed input-timing-dependent plasticity (ITDP) (Dudman et al., 2007).