The mediodorsal thalamus as a central hub in olfactory learning

食物偏好学习的社会传递是社会背景下食物选择学习的一个模型。STFP是一种基于食品安全信号社会传递的动物行为学相关的一次性学习行为。我们想要研究STFP学习在嗅觉皮质-丘脑-新皮层环路中的编码和检索，该环路涉及初级嗅觉或梨状皮质（PC）、丘脑中背侧（MDT）和眶额皮质（OFC）。PC-MDT-OFC （PMO）回路的所有三个组成部分在嗅觉引导的与学习和评估相关的行为中都起着关键作用。MDT接收来自腹侧苍白球的直接输入，这是一个与进食有关的经典享乐热点。这使得MDT在将奖励价值归因于PC和OFC处理的嗅觉刺激时处于中心位置。学习中环境的稳定表征需要神经元印痕集合的同步活动。全脑图谱最近发现了一个由相互依赖的区域印痕集合组成的印痕复合体。我们的中心假设是，MDT在STFP学习过程中作为pmo环路中处理奖励价值和引导注意到显著刺激的同步枢纽，从而促进印痕复合物的形成。根据这一建议，我们的两个实验室将对清醒小鼠PC、OFC和MDT中介导STFP学习编码和检索的神经元印痕集成进行纵向分析和操作。我们将使用最先进的成像（微型显微镜和双光子）和电生理（多位点电生理单元记录与神经像素探针）技术进行神经元活动的动态实时分析。区域间的光学和药理学操作将利用转基因和病毒工具进行电路特异性表达，以解决因果关系问题。我们将在三个不同的目标上共同努力：首先，我们将研究在编码和检索过程中操纵pmo环路中MDT输出的活动对行为结果的影响。其次，我们将利用成像技术纵向分析在中尺度STFP学习的编码和检索过程中，pmo环路中特定投射神经元群中稳定的行为和刺激相关的神经元活动模式的出现。在这里，我们期望纵向观察相同的神经元在STFP学习的不同阶段。第三，我们将在高时间分辨率下对STFP学习编码和检索过程中pmo回路中与行为和刺激相关的神经元活动模式进行多位点电生理单元记录。在这里，我们期望描述pmo环路不同区域功能连接的神经元群相互依赖和同步激活，以介导STFP学习的编码和检索。

Social transmission of food preference learning (STFP) is a model of food choice learning in a social context. STFP is an ethologically relevant rodent one-shot learning behavior based on the social transmission of a food safety signal. We want to study encoding and retrieval of STFP learning in an olfactory cortico-thalamic-neocortical loop involving the primary olfactory or piriform cortex (PC), the mediodorsal thalamus (MDT), and the orbitofrontal cortex (OFC). All three components of this PC-MDT-OFC (PMO)-loop have a critical role in olfactory-guided behavior related to learning and evaluation. The MDT receives direct inputs from the ventral pallidum, a canonic hedonic hotspot related to feeding. This puts the MDT at a central position when it comes to attributing reward value to olfactory stimuli processed in the PC and OFC. The stable representation of context in learning requires the synchronous activity of neuronal engram ensembles. Brain-wide mapping recently identified an engram complex consisting of interdependent regional engram ensembles. Our central hypothesis is that the MDT serves as a synchronizing hub for processing reward value and directing attention to salient stimuli in the PMO-loop during STFP learning, thereby facilitating engram complex formation. With this proposal, our two laboratories will perform longitudinal analysis and manipulation of neuronal engram ensembles mediating encoding and retrieval of STFP learning in the PC, OFC, and MDT in awake mice. We will use state-of-the-art imaging (miniscope and two-photon) and electrophysiological (multi-site electrophysiological unit recordings with neuropixel probes) techniques for the dynamic real-time analysis of neuronal activity. Interregional opto- and pharmacogenetic manipulations will utilize transgenic and viral tools for circuit-specific expression to tackle questions of causality. We will direct our joint effort at three different objectives: First, we will investigate the effect of manipulating the activity of MDT outputs in the PMO-loop during encoding and retrieval on behavioral outcome. Second, we will use imaging to longitudinally analyze the emergence of stable behavior- and stimulus-associated neuronal activity patterns of specified projection neuron populations in the PMO-loop during encoding and retrieval of STFP learning at the mesoscale. Here, we expect to longitudinally observe the same neurons over the different phases of STFP learning. Third, we will perform multi-site electrophysiological unit recordings of behavior- and stimulus-associated neuronal activity patterns in the PMO-loop during encoding and retrieval of STFP learning at high temporal resolution. Here, we expect to characterize the interdependent and synchronous activation of functionally connected neuronal ensembles in different regions of the PMO-loop to mediate encoding and retrieval of STFP learning.