In vivo modulation of a cortical functional sensory representation shortly after topical cholinergic agent application

Abstract

The aim of the present study was to determine whether cholinergic increase in the size of a functional representation (collective evoked response from a large population of neurons) can be observed shortly (within an hour) after treatment onset and whether nicotinic receptors can participate in this type of modulation. Cholinergic agonist application has been found previously to increase the response of a single cortical neuron to a stimulus. Also, pairing cholinergic basal forebrain stimulation with delivery of a tone has been reported to increase the size of that tone's functional representation. Whereas the increase in a single cortical neuron response can occur within seconds after cholinergic agonist application, to date the increase in the size of a functional representation has only been investigated within one to several weeks after the onset of pairing basal forebrain stimulation with tone delivery. Furthermore, primarily muscarinic receptors have been implicated in these types of changes in cortical activity. By using optical imaging of intrinsic signals in vivo, we found that the size of a whisker's functional representation in the primary somatosensory cortex of the rat increases substantially within 69 or 46 minutes after topical application of either a muscarinic or nicotinic agonist to the exposed cortex, respectively, and decreases within 23 minutes after topical application of a muscarinic antagonist. For each cholinergic agent, we verified that delivery of a cholinergic agent by means of topical application can lead to the agent's successful penetration through the cortical layers in the time allotted to complete an imaging experiment. Furthermore, the time course of penetration for each agent was characterized. Based on the combined imaging/penetration results, we speculate on potential sites of cholinergic action in the cortex. Irrespective of the exact mechanism of action, we demonstrate here that an increase in the size of a functional sensory representation can occur shortly by means of activation of either nicotinic or muscarinic receptors.