Abstract
Acetylcholine (ACh) signaling shapes neuronal circuit development and underlies specific aspects of cognitive functions and behaviors, including attention, learning, memory and motivation. During behavior, activation of muscarinic and nicotinic acetylcholine receptors (mAChRs and nAChRs) by ACh alters the activation state of neurons, and neuronal circuits most likely process information differently with elevated levels of ACh. In several brain regions, ACh has been shown to alter synaptic strength as well. By changing the rules for synaptic plasticity, ACh can have prolonged effects on and rearrange connectivity between neurons that outlasts its presence. From recent discoveries in the mouse, rat, monkey and human brain, a picture emerges in which the basal forebrain (BF) cholinergic system targets the neocortex with much more spatial and temporal detail than previously considered. Fast cholinergic synapses acting on a millisecond time scale are abundant in the mammalian cerebral cortex, and provide BF cholinergic neurons with the possibility to rapidly alter information flow in cortical microcircuits. Finally, recent studies have outlined novel mechanisms of how cholinergic projections from the BF affect synaptic strength in several brain areas of the rodent brain, with behavioral consequences. This review highlights these exciting developments and discusses how these findings translate to human brain circuitries.
Highlights
Neuromodulation of the neocortex by acetylcholine (ACh) shapes neuronal circuit development, but is crucial for sensory and cognitive behavior, such as sensory detection, attention, learning and memory (Dalley et al, 2004; Hasselmo and Giocomo, 2006; Sarter et al, 2009)
Despite the fact that we know for instance that cholinergic signaling in the prefrontal cortex (PFC) is involved in attention, very little is known about the neuronal circuit mechanisms involved
Using an anterograde viral labeling strategy based on cre-recombinase-dependent expression of GFP/YFP in cholineacetyl transferase (ChAT)-cre transgenic mice it is possible to address this issue (Wouterlood et al, 2014), and we recently found that different locations in the basal forebrain (BF) innervate superficial or deep lamina of PFC (Bloem et al, 2014)
Summary
Neuromodulation of the neocortex by acetylcholine (ACh) shapes neuronal circuit development, but is crucial for sensory and cognitive behavior, such as sensory detection, attention, learning and memory (Dalley et al, 2004; Hasselmo and Giocomo, 2006; Sarter et al, 2009). It is becoming clear that ACh is a slow neuromodulator, but recent evidence shows that it can instantly alter information flow by direct, fast point-to-point ACh synapses that target specific pyramidal neurons and interneurons and act on millisecond time scales (Arroyo et al, 2014). Recent findings on cholinergic modulation of human neocortical microcircuits suggest that in the human brain these mechanisms exist, which may prompt us to change our view on the cholinergic system as being merely a slow acting arousal system to one that includes a fast acting manipulation of cortical information flow important for sub-second cognitive operations. This review highlights recent evidence from rodent, monkey and human brain that show that the cholinergic system in the mammalian brain acts on a spatial and temporal scale that is much more detailed than previously considered
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