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

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.