Pathway-dependent plasticity at hippocampal CA1 pyramidal cells

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Synaptic plasticity mechanisms in hippocampal CA1 neurons are complex, since direct and indirect cortical inputs to distal and proximal dendrites are modulated by cholinergic and monoaminergic innervations. Spike-timing-dependent plasticity (STDP) critically depends on the timing of pre- and postsynaptic spikes and is an attractive, physiologically relevant model for learning and memory. When testing postsynaptic spike bursts alone (three action potentials induced by somatic current injections at 100 Hz) in acute slices at 0.1 Hz for 10 min, we unexpectably observed concurrent potentiation of subsequently evoked excitatory postsynaptic potentials (EPSPs) in stratum radiatum and oriens. To distinguish increases in EPSPs from those evoked by dendritic spikes, we will examine intrinsic membrane properties, NMDA receptors and postsynaptic Ca2+ signaling. Furthermore, stimulating a STDP protocol at 0.1 Hz for 10 min in stratum radiatum depotentiated LTP induced by spike bursts alone in stratum oriens but not vice versa. We will assess the timecourse of this heterosynaptic depotentiation, its activity dependence and reversibility. To identify the underlying mechanisms, we will consider pre- and/or postsynaptic loci, NMDA receptor kinetics, diffusible messengers, neuromodulators, G proteins and propagating Ca2+ waves. We expect to obtain insights into non-Hebbian forms of potentiation and heterosynaptic plasticity, which contribute to memory processing.