Hanson Meretta A, Bibi Noor, Safa Alireza, Nagarajan Devipriyanka, Marshall Alec H, Johantges Aidan C, Wester Jason C
Department of Neuroscience, The Ohio State University College of Medicine, Columbus, Ohio 43210.
Neuroscience Graduate Program, The Ohio State University, Columbus, Ohio 43210.
J Neurosci. 2025 Feb 19;45(8):e0737242024. doi: 10.1523/JNEUROSCI.0737-24.2024.
Pyramidal cells (PCs) in CA1 hippocampus can be classified by their radial position as deep or superficial and organize into subtype-specific circuits necessary for differential information processing. Specifically, superficial PCs receive fewer inhibitory synapses from parvalbumin (PV)-expressing interneurons than deep PCs, resulting in weaker feedforward inhibition of input from CA3 Schaffer collaterals. Using mice, we investigated mechanisms underlying CA1 PC differentiation and the development of this inhibitory circuit motif. We found that the transcriptional regulator SATB2, which is necessary for pyramidal cell differentiation in the neocortex, is selectively expressed in superficial PCs during early postnatal development. To investigate its role in CA1, we conditionally knocked out from pyramidal cells during embryonic development using both male and female mice. Loss of resulted in increased feedforward inhibition of CA3 Schaffer collateral input to superficial PCs, which matched that observed to deep PCs in control mice. Using paired whole-cell recordings between PCs and PV+ interneurons, we found this was due to an increase in the strength of unitary inhibitory synaptic connections from PV+ interneurons to mutant superficial PCs. Regulation of synapse strength was restricted to inhibitory synapses; excitatory synaptic connections from CA3 to CA1 PCs and CA1 PCs to PV+ interneurons were not affected by loss of Finally, we show that SATB2 expression in superficial PCs is necessary to suppress the formation of synapses from PV+ interneurons during synaptogenesis. Thus, early postnatal expression of SATB2 in superficial PCs is necessary for the development of biased feedforward inhibition in CA1.
海马体CA1区的锥体细胞（PCs）可根据其在径向的位置分为深层或浅层，并组织成不同亚型的特定回路，这些回路对于差异信息处理至关重要。具体而言，浅层PCs从表达小白蛋白（PV）的中间神经元接收的抑制性突触比深层PCs少，导致对来自CA3区谢弗侧支输入的前馈抑制较弱。我们利用小鼠研究了CA1区PCs分化以及这种抑制性回路模式形成的潜在机制。我们发现，转录调节因子SATB2在新皮层锥体细胞分化中是必需的，在出生后早期发育阶段，它在浅层PCs中选择性表达。为了研究其在CA1区的作用，我们在胚胎发育期间使用雄性和雌性小鼠，有条件地从小鼠锥体细胞中敲除SATB2。SATB2缺失导致对浅层PCs的CA3区谢弗侧支输入的前馈抑制增加，这与对照小鼠中观察到的深层PCs的情况相匹配。通过对PCs和PV+中间神经元进行配对全细胞记录，我们发现这是由于从PV+中间神经元到突变浅层PCs的单突触抑制性连接强度增加所致。突触强度的调节仅限于抑制性突触；从CA3区到CA1区PCs以及从CA1区PCs到PV+中间神经元的兴奋性突触连接不受SATB2缺失的影响。最后，我们表明浅层PCs中SATB2的表达对于在突触发生过程中抑制来自PV+中间神经元的突触形成是必要的。因此，出生后早期浅层PCs中SATB2的表达对于CA1区偏向性前馈抑制的发育是必要的。
