内稳态突触可塑性建立了联想记忆的特异性。
Homeostatic synaptic scaling establishes the specificity of an associative memory.
机构信息
Department of Biology, Brandeis University, Waltham, MA 02453, USA.
Department of Psychology, Brandeis University, Waltham, MA 02453, USA.
出版信息
Curr Biol. 2021 Jun 7;31(11):2274-2285.e5. doi: 10.1016/j.cub.2021.03.024. Epub 2021 Apr 1.
Correlation-based (Hebbian) forms of synaptic plasticity are crucial for the initial encoding of associative memories but likely insufficient to enable the stable storage of multiple specific memories within neural circuits. Theoretical studies have suggested that homeostatic synaptic normalization rules provide an essential countervailing force that can stabilize and expand memory storage capacity. Although such homeostatic mechanisms have been identified and studied for decades, experimental evidence that they play an important role in associative memory is lacking. Here, we show that synaptic scaling, a widely studied form of homeostatic synaptic plasticity that globally renormalizes synaptic strengths, is dispensable for initial associative memory formation but crucial for the establishment of memory specificity. We used conditioned taste aversion (CTA) learning, a form of associative learning that relies on Hebbian mechanisms within gustatory cortex (GC), to show that animals conditioned to avoid saccharin initially generalized this aversion to other novel tastants. Specificity of the aversion to saccharin emerged slowly over a time course of many hours and was associated with synaptic scaling down of excitatory synapses onto conditioning-active neuronal ensembles within gustatory cortex. Blocking synaptic scaling down in the gustatory cortex enhanced the persistence of synaptic strength increases induced by conditioning and prolonged the duration of memory generalization. Taken together, these findings demonstrate that synaptic scaling is crucial for sculpting the specificity of an associative memory and suggest that the relative strengths of Hebbian and homeostatic plasticity can modulate the balance between stable memory formation and memory generalization.
基于关联(海伯)的突触可塑性对于联想记忆的初始编码至关重要,但不足以使神经回路中稳定存储多个特定记忆。理论研究表明,自我平衡的突触归一化规则提供了一种必要的抗衡力量,可以稳定和扩展记忆存储容量。尽管已经识别和研究了这种自我平衡机制数十年,但缺乏它们在联想记忆中起重要作用的实验证据。在这里,我们表明,突触缩放是一种广泛研究的自我平衡突触可塑性形式,它可以全局重新归一化突触强度,对于初始联想记忆形成是可有可无的,但对于建立记忆特异性却是至关重要的。我们使用条件味觉厌恶(CTA)学习,这是一种依赖于味觉皮层(GC)中海伯机制的联想学习形式,表明对蔗糖产生厌恶条件反射的动物最初会将这种厌恶泛化到其他新的味觉上。对蔗糖的厌恶特异性是在数小时的时间过程中缓慢出现的,与味觉皮层中兴奋性突触对 Conditioning-active 神经元集合的突触缩放有关。阻断味觉皮层中的突触缩放会增强 Conditioning 诱导的突触强度增加的持久性,并延长记忆泛化的持续时间。总之,这些发现表明,突触缩放对于塑造联想记忆的特异性至关重要,并表明海伯和自我平衡可塑性的相对强度可以调节稳定记忆形成和记忆泛化之间的平衡。
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