The role of the lateral entorhinal cortex in olfactory information processing

嗅觉线索提供了丰富的信息，当地的环境，关键的各种行为，如食物的搜索，社会交往和捕食者回避。在哺乳动物中，嗅觉信息最初在嗅球（OB）中处理，随后在初级嗅觉（梨状）皮层（PCx）中编码。与OB和PCx中嗅觉信息处理的详细知识相反，对更高区域（外侧内嗅皮层（LEC）和海马）的了解要少得多，这些区域被认为直接调节依赖于气味记忆和气味引导导航的行为。在这个项目中，我将使用多站点电生理记录和细胞类型特异性光遗传学操作，以确定嗅觉信息是如何在清醒小鼠的内鼻-海马网络中处理的。LEC接收两个来源的嗅觉输入：直接投射从OB二尖瓣细胞和间接投射通过PCx。这些输入信号与第2层的LEC主细胞的两种亚型相联系：“扇形”细胞，它向齿状回（DG）和锥体细胞发出直接投射，投射到海马CA 1区。气味引导导航依赖于辨别气味强度变化的能力。OB响应是浓度依赖性的，然而，PCx响应最近已被证明在很大程度上是不变的气味浓度。我假设，直接OB-LEC预测是至关重要的气味强度编码的处理在内鼻-海马network.In初步实验中，我建立了一个准备，以实现横向访问LEC清醒，行为小鼠，允许调查嗅觉处理跨层。同时电生理记录从OB，LEC，DG和CA 1或OB，PCx和LEC与高密度的细胞外探针将允许调查嗅觉处理在高时间分辨率跨区域。电生理记录将与细胞类型特异性光遗传标记和操作相补充，以在气味引导行为期间识别和干扰电路的不同组件。为了实现这一点，我已经确定了cre驱动小鼠专门针对LEC层2风扇和锥体细胞。最终，该项目将建立气味身份和强度在LEC和海马中处理和编码的机制。在气味引导的任务中，内鼻-海马网络中关键通路的光遗传学扰动将揭示它们对行为不同方面的重要性。阐明嗅觉处理的性质，在内鼻-海马网络将导致更好地理解的途径管理陈述性记忆和感觉引导导航。除了嗅觉处理，该项目还提供了对LEC微电路以及内鼻-海马相互作用的新见解。

Olfactory cues provide rich information about the local environment, critical for a diverse range of behaviors, such as food seeking, social interactions and predator avoidance. In mammals, olfactory information is initially processed in the olfactory bulb (OB) and subsequently encoded in primary olfactory (piriform) cortex (PCx). In contrast to detailed knowledge of olfactory information processing in OB and PCx, much less is known about higher areas, the lateral entorhinal cortex (LEC) and hippocampus, that are thought to directly regulate behaviors relying on odor memory and odor-guided navigation. In this project, I will use multi-site electrophysiological recordings and cell-type specific optogenetic manipulations to determine how olfactory information is processed across the entorhinal-hippocampal network in awake mice.The LEC receives two sources of olfactory input: direct projections from OB mitral cells and indirect projections via PCx. These inputs contact two subtypes of LEC principal cells in layer 2: “fan” cells which send direct projections to the dentate gyrus (DG) and pyramidal cells that project to the CA1 region of hippocampus. Odor-guided navigation relies on the ability to discriminate changes in odor intensity. OB responses are concentration-dependent, however, PCx responses have recently been shown to be largely invariant to odor concentration. I hypothesize that direct OB-LEC projections are critical for the processing of odor intensity coding in the entorhinal-hippocampal network.In preliminary experiments I established a preparation to achieve lateral access to the LEC in awake, behaving mice, allowing to investigate olfactory processing across layers. Simultaneous electrophysiological recordings from OB, LEC, DG and CA1 or OB, PCx and LEC with high-density extracellular probes will allow to investigate olfactory processing across areas at high temporal resolution. Electrophysiological recordings will be complemented with cell-type specific optogenetic tagging and manipulations to identify and perturb distinct components of the circuit during odor-guided behavior. To accomplish this, I have identified cre driver mice to specifically target LEC layer 2 fan and pyramidal cells. Ultimately, this project will establish mechanisms by which odor identity and intensity are processed and encoded in the LEC and hippocampus. Optogenetic perturbations of key pathways in the entorhinal-hippocampal network during odor-guided tasks will reveal their importance for different aspects of behavior. Elucidating the nature of olfactory processing in the entorhinal-hippocampal network will lead to a better understanding of pathways governing declarative memory and sensory-guided navigation. In addition to olfactory processing, the project provides new insight into LEC microcircuits, as well as entorhinal-hippocampal interactions.