title: Impact of basal forebrain cholinergic inputs on basolateral amygdala neurons.
abstract: In addition to innervating the cerebral cortex, basal forebrain cholinergic (BFc) neurons send a dense projection to the basolateral nucleus of the amygdala (BLA). In this study, we investigated the effect of near physiological acetylcholine release on BLA neurons using optogenetic tools and in vitro patch-clamp recordings. Adult transgenic mice expressing cre-recombinase under the choline acetyltransferase promoter were used to selectively transduce BFc neurons with channelrhodopsin-2 and a reporter through the injection of an adeno-associated virus. Light-induced stimulation of BFc axons produced different effects depending on the BLA cell type. In late-firing interneurons, BFc inputs elicited fast nicotinic EPSPs. In contrast, no response could be detected in fast-spiking interneurons. In principal BLA neurons, two different effects were elicited depending on their activity level. When principal BLA neurons were quiescent or made to fire at low rates by depolarizing current injection, light-induced activation of BFc axons elicited muscarinic IPSPs. In contrast, with stronger depolarizing currents, eliciting firing above ∼ 6-8 Hz, these muscarinic IPSPs lost their efficacy because stimulation of BFc inputs prolonged current-evoked afterdepolarizations. All the effects observed in principal neurons were dependent on muscarinic receptors type 1, engaging different intracellular mechanisms in a state-dependent manner. Overall, our results suggest that acetylcholine enhances the signal-to-noise ratio in principal BLA neurons. Moreover, the cholinergic engagement of afterdepolarizations may contribute to the formation of stimulus associations during fear-conditioning tasks where the timing of conditioned and unconditioned stimuli is not optimal for the induction of synaptic plasticity.
authors.affiliation: Center for Molecular and Behavioral Neuroscience, Rutgers, The State University, Newark, New Jersey 07102.
authors.forename: Cagri T
authors.initials: CT
authors.lastname: Unal
authors.affiliation: Center for Molecular and Behavioral Neuroscience, Rutgers, The State University, Newark, New Jersey 07102.
authors.forename: Denis
authors.initials: D
authors.lastname: Pare
authors.affiliation: Center for Molecular and Behavioral Neuroscience, Rutgers, The State University, Newark, New Jersey 07102 laszloz@andromeda.rutgers.edu.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Zaborszky
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000679:Amygdala / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D059329:Cholinergic Neurons / Q000378:metabolism* / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials; D051379:Mice; D016548:Prosencephalon / Q000378:metabolism* / Q000502:physiology; D043643:Receptor, Muscarinic M1 / Q000378:metabolism
chemical_list: D043643:Receptor, Muscarinic M1; D000109:Acetylcholine
keywords: acetylcholine; amygdala; emotion; fear; memory; state dependence