PDF(Pubmed)
Abstract：
Hippocampal CA3 is traditionally conceptualized as a brain region within a unidirectional feedforward trisynaptic pathway that links major hippocampal subregions. Recent genomic and viral tracing studies indicate that the anatomical connectivity of CA3 and the trisynaptic pathway is more complex than initially expected and suggests that there may be cell type-specific input gradients throughout the three-dimensional hippocampal structure. In several recent studies using multiple viral tracing approaches, we describe subdivisions of the subiculum complex and ventral hippocampal CA1 that show significant back projections to CA1 and CA3 excitatory neurons. These novel connections form \"noncanonical\" circuits that run in the opposite direction relative to the well-characterized feedforward pathway. Diverse subtypes of GABAergic inhibitory neurons participate within the trisynaptic pathway. In the present study, we have applied monosynaptic retrograde viral tracing to examine noncanonical synaptic inputs from CA1 and subicular complex to the inhibitory neuron in hippocampal CA3. We quantitatively mapped synaptic inputs to CA3 inhibitory neurons to understand how they are connected within and beyond the hippocampus formation. Major brain regions that provide typical inputs to CA3 inhibitory neurons include the medial septum, the dentate gyrus, the entorhinal cortex, and CA3. Noncanonical inputs from ventral CA1 and subicular complex to CA3 inhibitory neurons follow a proximodistal topographic gradient with regard to CA3 subregions. We find novel noncanonical circuit connections between inhibitory CA3 neurons and ventral CA1, subiculum complex, and other brain regions. These results provide a new anatomical connectivity basis to further study the function of CA3 inhibitory neurons.
摘要：
海马CA3传统上被概念化为单向前馈三突触通路内的大脑区域，该通路连接主要的海马亚区。最近的基因组和病毒追踪研究表明，CA3和三突触途径的解剖连接比最初预期的更复杂，并表明在整个三维海马结构中可能存在细胞类型特异性输入梯度。在最近使用多种病毒追踪方法的几项研究中，我们描述了下膜复合体和腹侧海马CA1的细分，这些细分显示了对CA1和CA3兴奋性神经元的显着向后投射。这些新颖的连接形成了“非规范”电路，这些电路相对于特征良好的前馈路径沿相反的方向运行。GABA能抑制性神经元的不同亚型参与三突触途径。在本研究中,我们已经应用单突触逆行病毒示踪来检查CA1和囊下复合物对海马CA3抑制性神经元的非规范突触输入。我们定量地将突触输入映射到CA3抑制性神经元，以了解它们如何在海马形成内外连接。为CA3抑制性神经元提供典型输入的主要大脑区域包括内侧隔膜，齿状回,内嗅皮层，和CA3。从腹侧CA1和囊下复合物到CA3抑制性神经元的非规范输入遵循关于CA3子区域的近端远端地形梯度。我们发现抑制性CA3神经元和腹侧CA1，下膜复合体之间的新型非规范回路连接，和其他大脑区域。这些结果为进一步研究CA3抑制性神经元的功能提供了新的解剖学连接基础。
