Basal forebrain mediated modulation of information processing in olfactory cortical areas in awake behaving mice

感觉信息的吸收和处理是大脑的一些中心任务。感官输入通过几个中继站穿梭，这些中继站都对这些信息进行了大量的处理和调制，以适应动物的需要。状态依赖性适应可以由所谓的经典神经调节中心介导，例如基底前脑（BF）或蓝斑，它们沿着感觉通路支配许多不同的大脑区域。BF是一个特别有趣的大脑区域，因为它对感觉增益调制或感受野锐化的影响可以深刻地影响行为和认知过程。较新的研究表明，状态依赖性适应可能是由于在不同的皮层和皮层下处理水平的调制过程的复杂的相互作用。在嗅觉系统中，关于BF神经调节的研究主要集中在嗅球（OB）水平，嗅球是中央嗅觉信息处理的第一阶段，而高级嗅觉皮层区域中的调节在很大程度上被忽视，这可能是由于缺乏BF到嗅觉皮层连接特征的详细知识以及这些脑深部区域的可达性。我们提出了一个详细的调查BF影响的两个最前面的嗅觉皮层区域，前嗅核（AON）和前梨状皮质（APC）。这些皮层嗅觉区似乎是特别重要的，因为他们不仅接受强烈的嗅觉感觉输入，以及从神经调节中心的离心投射，但他们也发送大量的投射回OB。首先，我们将研究离心BF AON/APC连接使用双色电路跟踪，问BF神经元亚型和亚核主要投射到嗅觉皮层，如果BF神经元投射到AON和APC形成单独或重叠的人群。此外，我们将使用这种追踪方法来使用光遗传致动器特异性地激活AON或APC投射BF神经元，同时记录麻醉以及清醒行为小鼠中的嗅觉皮层神经元活动。在第二组实验中，我们将询问AON或APC中BF纤维的特定激活或抑制如何影响嗅觉行为。

Sensory information uptake and processing are some of the central tasks of the brain. Sensory input is shuttled through several relay stations that all heavily process and modulate this information to adapt it to the animal's needs. State-dependent adaptations can be mediated by so-called classical neuromodulatory centres like the basal forebrain (BF) or locus coeruleus that innervate many different brain areas along the sensory pathways. The BF is a particularly interesting brain area since its influence on e.g. sensory gain modulation or the sharpening of receptive fields can profoundly influence behavioural as well as cognitive processes. Newer studies suggest that state-dependent adaptations are probably due to a complex interplay of modulatory processes at different cortical and subcortical processing levels. In the olfactory system, research on BF neuromodulation has been focused mainly at the level of the olfactory bulb (OB), the first stage of central olfactory information processing while modulation in higher olfactory cortical areas has been largely ignored, probably due to a lack of detailed knowledge of BF to olfactory cortex connection characteristics as well as accessibility of these deep brain areas.Here, we propose a detailed investigation of BF influence on the two most anterior olfactory cortical regions, the anterior olfactory nucleus (AON) and the anterior piriform cortex (APC). These cortical olfactory areas seem to be of special importance since they do not only receive strong olfactory sensory input as well as centrifugal projections from neuromodulatory centres but they also send numerous projections back to the OB. First, we will investigate the centrifugal BF to AON/APC connectivity using dual-colour circuit tracing, asking which BF neuronal subtypes and subnuclei are predominantly projecting to the olfactory cortex and if BF neurons projecting to AON and APC form separate or overlapping populations. Furthermore, we will use this tracing approach to specifically activate AON or APC projecting BF neurons using optogenetic actuators while recording olfactory cortical neuronal activity in both anesthetized as well as awake behaving mice. In the second set of experiments, we will ask how specific activation or inhibition of BF fibres in AON or APC affects olfactory behaviour.