Keller Martin K, Draguhn Andreas, Both Martin, Reichinnek Susanne
Institute of Physiology and Pathophysiology, University of Heidelberg Heidelberg, Germany.
Institute of Physiology and Pathophysiology, University of Heidelberg Heidelberg, Germany ; Mediterranean Institute of Neurobiology (INMED), INSERM Marseille, France.
Front Neural Circuits. 2015 May 18;9:21. doi: 10.3389/fncir.2015.00021. eCollection 2015.
Memory formation is associated with the generation of transiently stable neuronal assemblies. In hippocampal networks, such groups of functionally coupled neurons express highly ordered spatiotemporal activity patterns which are coordinated by local network oscillations. One of these patterns, sharp wave-ripple complexes (SPW-R), repetitively activates previously established groups of memory-encoding neurons, thereby supporting memory consolidation. This function implies that repetition of specific SPW-R induces plastic changes which render the underlying neuronal assemblies more stable. We modeled this repetitive activation in an in vitro model of SPW-R in mouse hippocampal slices. Weak electrical stimulation upstream of the CA3-CA1 networks reliably induced SPW-R of stereotypic waveform, thus representing re-activation of similar neuronal activity patterns. Frequent repetition of these patterns (100 times) reduced the variance of both, evoked and spontaneous SPW-R waveforms, indicating stabilization of pre-existing assemblies. These effects were most pronounced in the CA1 subfield and depended on the timing of stimulation relative to spontaneous SPW-R. Additionally, plasticity of SPW-R was blocked by application of a NMDA receptor antagonist, suggesting a role for associative synaptic plasticity in this process. Thus, repetitive activation of specific patterns of SPW-R causes stabilization of memory-related networks.
记忆形成与瞬时稳定的神经元集群的产生有关。在海马体网络中，这类功能耦合的神经元群表现出高度有序的时空活动模式，这些模式由局部网络振荡协调。其中一种模式，即尖波-涟漪复合体（SPW-R），反复激活先前建立的记忆编码神经元群，从而支持记忆巩固。这一功能意味着特定SPW-R的重复会诱导可塑性变化，使潜在的神经元集群更加稳定。我们在小鼠海马体切片的SPW-R体外模型中模拟了这种重复激活。在CA3-CA1网络上游进行弱电刺激可可靠地诱导出具有刻板波形的SPW-R，从而代表类似神经元活动模式的重新激活。这些模式的频繁重复（100次）降低了诱发和自发SPW-R波形的方差，表明先前存在的集群得到了稳定。这些效应在CA1子区域最为明显，并取决于刺激相对于自发SPW-R的时间。此外，应用NMDA受体拮抗剂可阻断SPW-R的可塑性，这表明在这一过程中联想性突触可塑性发挥了作用。因此，特定模式的SPW-R的重复激活会导致记忆相关网络的稳定。
