Input-selective potentiation and rebalancing of primary sensory cortex afferents by endogenous acetylcholine

Acetylcholine (ACh) plays important roles in the modulation of activity and plasticity of primary sensory cortices, thus influencing sensory detection and integration. We examined this in urethane-anesthetized rats, comparing cholinergic modulation of short latency, large amplitude field postsynaptic potentials (fPSPs) in the visual cortex (V1) evoked by stimulation of the ipsilateral lateral geniculate nucleus (LGN), reflecting direct thalamocortical inputs, with longer latency, smaller amplitude fPSPs elicited by contralateral LGN stimulation, reflecting indirect, polysynaptic inputs. Basal forebrain (BF) stimulation (100 Hz) produced a significant (45%), gradually developing potentiation of the smaller, contralateral fPSPs, while ipsilateral fPSPs showed less enhancement (15%), shifting the relative strength of dominant/ipsi- and weaker/contralateral inputs to V1. Systemic or local, cortical blockade of muscarinic receptors (scopolamine) reduced potentiation of contralateral fPSP without affecting ipsilateral enhancement, thus preventing the relative amplification of contralateral inputs following BF stimulation. Systemic nicotinic receptor blockade (mecamylamine) resulted in depression of ipsilateral, and reduced enhancement of contralateral fPSPs after BF stimulation. N-methyl-d-aspartate receptor blockade (systemic MK-801) abolished ipsilateral fPSP enhancement without affecting contralateral potentiation. Neither drug reduced the amplification of contralateral relative to ipsilateral signals in V1. In a second experiment in the barrel cortex, BF stimulation enhanced multiunit activity elicited by whisker deflection in a muscarinic-sensitive manner. Similar to the observations in V1, this effect was more pronounced for weaker multiunit activity driven by a surround whisker than activity following principal whisker deflection. These experiments demonstrate that ACh release following BF stimulation exerts surprisingly selective effects to amplify non-dominant inputs to sensory cortices. We suggest that, by diminishing the imbalance between different afferent signals, ACh release during states of behavioral activation acts to induce a long-lasting facilitation of the detection and/or integration of signals in primary sensory fields of the cortical mantle.