State-dependent changes in olfactory cortical networks via cholinergic modulation

Abstract

Activity in sensory cortical networks reflects both peripheral sensory input and intra- and inter-cortical network input. How sensory cortices balance these diverse inputs to provide relatively stable, accurate representations of the external world is not well understood. Furthermore, neuromodulation could alter the balance of these inputs in a state- and behavior-dependent manner. Here, we used optogenetic stimulation to directly assay the relative strength of bottom-up (olfactory bulb) and top-down (lateral entorhinal cortex) synaptic inputs to piriform cortex in freely moving rats. Optotrodes in the piriform cortex were used to test the relative strength of these two inputs, in separate animals, with extracellular, monosynaptic evoked potentials. The results suggest a rapid state-dependent shift in the balance of bottom-up and top-down inputs to PCX, with enhancement in the strength of lateral entorhinal cortex synaptic input and stability or depression of olfactory bulb synaptic input during slow-wave sleep compared to waking. The shift is in part due to a state-dependent change in cholinergic tone as assessed with fiber photometry of GCaMP6 fluorescence in basal forebrain ChAT+ neurons, and blockade of the state-dependent synaptic shift with cholinergic muscarinic receptor activation.