Pathway-dependent plasticity at hippocampal CA1 pyramidal cells

海马CA 1区神经元的突触可塑性机制是复杂的，因为对远端和近端树突的直接和间接皮质输入受到胆碱能和单胺能神经支配的调制。尖峰时间依赖性可塑性（STDP）严重依赖于突触前和突触后尖峰的时间，是一个有吸引力的，生理相关的学习和记忆模型。当测试突触后锋电位爆发单独（三个动作电位诱导的躯体电流注射在100 Hz）在急性切片在0.1 Hz的10分钟，我们意想不到地观察到并发增强随后诱发兴奋性突触后电位（EPSP）在放射层和oriens。为了区分增加EPSP诱发的树突棘波，我们将研究内在膜特性，NMDA受体和突触后Ca 2+信号。此外，在0.1 Hz刺激辐射层STDP协议10分钟，去增强LTP单独的棘波爆发在定向层，但不是反之亦然。我们将评估这种异突触去电位的时程，其活动依赖性和可逆性。为了确定潜在的机制，我们将考虑前和/或突触后位点，NMDA受体动力学，扩散信使，神经调质，G蛋白和传播Ca 2+波。我们希望获得洞察力的非赫布形式的增强和异突触可塑性，这有助于记忆处理。

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.