Vantomme Gil, Devienne Gabrielle, Hull Jacob M, Huguenard John R
Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA.
bioRxiv. 2025 Feb 3:2024.05.31.596906. doi: 10.1101/2024.05.31.596906.
Medial prefrontal cortex (mPFC) and hippocampus are critical for memory retrieval, decision making and emotional regulation. While ventral CA1 (vCA1) shows direct and reciprocal connections with mPFC, dorsal CA1 (dCA1) forms indirect pathways to mPFC, notably via the thalamic Reuniens nucleus (Re). Neuroanatomical tracing has documented structural connectivity of this indirect pathway through Re however, its functional operation is largely unexplored. Here we used and electrophysiology along with optogenetics to address this question. Whole-cell patch-clamp recordings in acute mouse brain slices revealed both monosynaptic excitatory responses and disynaptic feedforward inhibition at Re-mPFC synapses. However, we also identified a novel prolonged excitation of mPFC by Re. These early monosynaptic and late recurrent components are in marked contrast to the primarily feedforward inhibition characteristic of thalamic inputs to neocortex. Local field potential recordings in mPFC brain slices revealed prolonged synaptic activity throughout all cortical lamina upon Re activation, with the late excitation enhanced by blockade of parvalbumin neurons and GABARs. Neuropixels recordings in head-fixed awake mice revealed a similar prolonged excitation of mPFC units by Re activation. In summary, Re output produces recurrent feedforward excitation within mPFC suggesting a potent amplification system in the Re-mPFC network. This may facilitate amplification of dCA1->mPFC signals for which Re acts as the primary conduit, as there is little direct connectivity. In addition, the capacity of mPFC neurons to fire bursts of action potentials in response to Re input suggests that these synapses have a high gain.
The interactions between medial prefrontal cortex and hippocampus are crucial for memory formation and retrieval. Yet, it is still poorly understood how the functional connectivity of direct and indirect pathways underlies these functions. This research explores the synaptic connectivity of the indirect pathway through the Reuniens nucleus of the thalamus using electrophysiological recordings and optogenetic manipulations. The study found that Reuniens stimulation recruits recurrent and long-lasting activity in mPFC - a phenomenon not previously recorded. This recurrent activity might create a temporal window ideal for coincidence detection and be an underlying mechanism for memory formation and retrieval.
内侧前额叶皮质（mPFC）和海马体对记忆检索、决策制定和情绪调节至关重要。虽然腹侧海马体1区（vCA1）与mPFC有直接的相互连接，但背侧海马体1区（dCA1）通过丘脑 reunions核（Re）形成到mPFC的间接通路。神经解剖学追踪记录了这条通过Re的间接通路的结构连接，然而，其功能运作在很大程度上尚未被探索。在这里，我们使用 和 电生理学以及光遗传学来解决这个问题。急性小鼠脑片的全细胞膜片钳记录揭示了Re-mPFC突触处的单突触兴奋性反应和双突触前馈抑制。然而，我们还发现了Re对mPFC的一种新的延长兴奋。这些早期的单突触和晚期的反复成分与丘脑输入到新皮质的主要前馈抑制特征形成鲜明对比。mPFC脑片的局部场电位记录显示，在Re激活后，所有皮质层都有延长的突触活动，通过阻断小白蛋白神经元和GABARs可增强晚期兴奋。头部固定清醒小鼠的神经像素记录显示，Re激活对mPFC单位有类似的延长兴奋。总之，Re输出在mPFC内产生反复前馈兴奋，表明Re-mPFC网络中有一个强大的放大系统。这可能有助于放大dCA1->mPFC信号，因为Re是主要通道，且它们之间几乎没有直接连接。此外，mPFC神经元对Re输入产生动作电位爆发的能力表明这些突触具有高增益。
内侧前额叶皮质和海马体之间的相互作用对记忆形成和检索至关重要。然而，直接和间接通路的功能连接如何支撑这些功能仍知之甚少。本研究使用电生理记录和光遗传学操作，探索通过丘脑reunions核的间接通路的突触连接。研究发现，Reunions刺激在mPFC中引发反复和持久的活动——这是以前未记录到的现象。这种反复活动可能创造一个适合巧合检测的时间窗口，是记忆形成和检索的潜在机制。
