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by Keyword: Acetylcholine


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Amil, Adrián F., Puigbó, J.-Y., Verschure, P., (2020). Cholinergic control of chaos and evidence sensitivity in a neocortical model of perceptual decision-making Biomimetic and Biohybrid Systems 9th International Conference, Living Machines 2020 (Lecture Notes in Computer Science) , Springer International Publishing (Freiburg, Germany) 12413, 92-96

Perceptual decision-making in the brain is commonly modeled as a competition among tuned cortical populations receiving stimulation according to their perceptual evidence. However, the contribution of evidence on the decision-making process changes through time. In this regard, the mechanisms controlling the sensitivity to perceptual evidence remain unknown. Here we explore this issue by using a biologically constrained model of the neocortex performing a dual-choice perceptual discrimination task. We combine mutual and global GABAergic inhibition, which are differentially regulated by acetylcholine (ACh), a neuromodulator linked to enhanced stimulus discriminability. We find that, while mutual inhibition determines the phase-space separation between two stable attractors representing each stimulus, global inhibition controls the formation of a chaotic attractor in-between the two, effectively protecting the weakest stimulus. Hence, under low ACh levels, where global inhibition dominates, the decision-making process is chaotic and less determined by the difference between perceptual evidences. On the contrary, under high ACh levels, where mutual inhibition dominates, the network becomes very sensitive to small differences between stimuli. Our results are in line with the putative role of ACh in enhanced stimulus discriminability and suggest that ACh levels control the sensitivity to sensory inputs by regulating the amount of chaos.

Keywords: Acetylcholine, Cortical model, Decision-making, Chaos


Puigbò, J. Y., Maffei, G., Herreros, I., Ceresa, M., González Ballester, M. A., Verschure, P. F. M. J., (2018). Cholinergic behavior state-dependent mechanisms of neocortical gain control: A neurocomputational study Molecular Neurobiology 55, (1), 249-257

The embodied mammalian brain evolved to adapt to an only partially known and knowable world. The adaptive labeling of the world is critically dependent on the neocortex which in turn is modulated by a range of subcortical systems such as the thalamus, ventral striatum, and the amygdala. A particular case in point is the learning paradigm of classical conditioning where acquired representations of states of the world such as sounds and visual features are associated with predefined discrete behavioral responses such as eye blinks and freezing. Learning progresses in a very specific order, where the animal first identifies the features of the task that are predictive of a motivational state and then forms the association of the current sensory state with a particular action and shapes this action to the specific contingency. This adaptive feature selection has both attentional and memory components, i.e., a behaviorally relevant state must be detected while its representation must be stabilized to allow its interfacing to output systems. Here, we present a computational model of the neocortical systems that underlie this feature detection process and its state-dependent modulation mediated by the amygdala and its downstream target the nucleus basalis of Meynert. In particular, we analyze the role of different populations of inhibitory interneurons in the regulation of cortical activity and their state-dependent gating of sensory signals. In our model, we show that the neuromodulator acetylcholine (ACh), which is in turn under control of the amygdala, plays a distinct role in the dynamics of each population and their associated gating function serving the detection of novel sensory features not captured in the state of the network, facilitating the adjustment of cortical sensory representations and regulating the switching between modes of attention and learning.

Keywords: Acetylcholine, Inhibitory network, Neocortical circuits, Neuromodulation


Gorostiza, P., Isacoff, E.Y., (2011). Photoswitchable ligand-gated ion channels Photosensitive molecules for controlling biological function (ed. Chambers, J. J. , Kramer, R. H.), Springer (Saskatoon, Canada) 55, 267-285

Ligand-activated proteins can be controlled with light by means of synthetic photoisomerizable tethered ligands (PTLs). The application of PTLs to ligand-gated ion channels, including the nicotinic acetylcholine receptor and ionotropic glutamate receptors, is reviewed with emphasis on rational photoswitch design and the mechanisms of optical switching. Recently reported molecular dynamic methods allow simulation with high reliability of novel PTLs for any ligand-activated protein whose structure is known.

Keywords: Nicotinic acetylcholine receptor, Kainate receptor, Glutamate receptor, Photoisomerizable tether ligand (PTL), Optical switch, Nanotoggle, Azobenzene, Neurobiology,, Nanoengineering, Nanomedicine


Gorostiza, P., Isacoff, E. Y., (2008). Optical switches for remote and noninvasive control of cell signaling Science 322, (5900), 395-399

Although the identity and interactions of signaling proteins have been studied in great detail, the complexity of signaling networks cannot be fully understood without elucidating the timing and location of activity of individual proteins. To do this, one needs a means for detecting and controlling specific signaling events. An attractive approach is to use light, both to report on and control signaling proteins in cells, because light can probe cells in real time with minimal damage. Although optical detection of signaling events has been successful for some time, the development of the means for optical control has accelerated only recently. Of particular interest is the development of chemically engineered proteins that are directly sensitive to light.

Keywords: Ion channels, Acetylcholine receptor, Glutamate-receptor, Potassium channel, K+ channel, Light, Neurons, Channelrhodopsin-2, Manipulation, Activation