Cholinergic | EPFL Graph Search

Cholinomimetic Cholinergic agents are compounds which mimic the action of acetylcholine and/or butyrylcholine. In general, the word "choline" describes the various quaternary ammonium salts containing the N,N,N-trimethylethanolammonium cation. Found in most animal tissues, choline is a primary component of the neurotransmitter acetylcholine and functions with inositol as a basic constituent of lecithin. Choline also prevents fat deposits in the liver and facilitates the movement of fats into cells. The parasympathetic nervous system, which uses acetylcholine almost exclusively to send its messages, is said to be almost entirely cholinergic. Neuromuscular junctions, preganglionic neurons of the sympathetic nervous system, the basal forebrain, and brain stem complexes are also cholinergic, as are the receptor for the merocrine sweat glands. In neuroscience and related fields, the term cholinergic is used in these related contexts:

A substance (or ligand) is cholinergic if it is

Neuromodulation of neocortical microcircuitry: a multi-scale framework to model the effects of cholinergic release

Cristina Colangelo

Neuromodulation of neocortical microcircuits is one of the most fascinatingand mysterious aspects of brain physiology. Despite over a century of research,the neuroscientific community has yet to uncover the fundamentalbiological organizing principles underlying neuromodulatory release. Phylogenetically,Acetylcholine (ACh) is perhaps the oldest neuromodulator,and one of the most well-studied. ACh regulates the physiology of neuronsand synapses, and modulates neural microcircuits to bring about areconfiguration of global network states. ACh is known to support cognitiveprocesses such as learning and memory, and is involved in the regulationof arousal, attention and sensory processing. While the effects of ACh inthe neocortex have been characterized extensively, integrated knowledge ofits mechanisms of action is lacking. Furthermore, the ways in which AChis released from en-passant axons originating in subcortical nuclei are stilldebatable. Simulation-based paradigms play an important role in testingscientific hypotheses, and provide a useful framework to integrate what isalready known and systematically explore previously uncharted territory.Importantly, data-driven computational approaches highlight gaps in currentknowledge and guide experimental research. To this end, I developed amulti-scale model of cholinergic innervation of rodent somatosensory cortexcomprising two distinct sets of ascending projections implementing eithersynaptic (ST) or volumetric transmission (VT). The model enables the projectiontypes to be combined in arbitrary proportions, thus permitting investigationsof the relative contributions of these two transmission modalities.Using our ACh model, we find that the two modes of cholinergic release actin concert and have powerful desynchronizing effects on microcircuit activity.Furthermore we show that this modeling framework can be extendedto other neuromodulators, such as dopamine and serotonin, with minimalconstraining data. In summary, our results suggest a more nuanced view ofneuromodulation in which multiple modes of transmitter release - ST vs VT- are required to produce synergistic functional effects.

EPFL2022

Cholinergic Signals in Mouse Barrel Cortex during Active Whisker Sensing

Sylvain Crochet, Emmanuel Albert Eggermann, Yves Kremer, Carl Petersen

Internal brain states affect sensory perception, cognition, and learning. Many neocortical areas exhibit changes in the pattern and synchrony of neuronal activity during quiet versus active behaviors. Active behaviors are typically associated with desynchronized cortical dynamics. Increased thalamic firing contributes importantly to desynchronize mouse barrel cortex during active whisker sensing. However, a whisking-related cortical state change persists after thalamic inactivation, which is mediated at least in part by acetylcholine, as we show here by using whole-cell recordings, local pharmacology, axonal calcium imaging, and optogenetic stimulation. During whisking, we find prominent cholinergic signals in the barrel cortex, which suppress spontaneous cortical activity. The desynchronized state of barrel cortex during whisking is therefore driven by at least two distinct signals with opposing functions: increased thalamic activity driving glutamatergic excitation of the cortex and increased cholinergic input suppressing spontaneous cortical activity.

Elsevier2014

(Visual) Endophenotypes in schizophrenia research

Ophélie Gladys Favrod, Michael Herzog, Albulena Jashari-Shaqiri, Maya Roinishvili

Objective: Schizophrenia is a heterogeneous disease strongly influenced by genetic disposition. However, genetic studies have shown that each single nucleotide polymorphism (SNP) contributes very little to the disease. For this reason, endophenotypes, located in between the genetic and clinical level, have become of great interest. Due to its heterogeneity, schizophrenia is likely not caused by one abnormality. Here, we asked the question to what extent deficits in various endophenotypes tap into the same deficits of schizophrenia. Methods: We tested schizophrenia patients, their relatives, and controls with a battery of perceptual and cognitive tests, such as visual backward masking, out of body experience, the Wisconsin Card Sorting Test (WCST), verbal fluency, and the continous performance task (CPT). Results: First, we found that visual backward masking is an extremely sensitive endophenotype of schizophrenia. Deficits are specific to the psychosis spectrum and not evident in depressive patients and abstinent alcoholics. As expected from an endophenotype, not only the patients but also their siblings show clear performance deficits, as well as adolescents with psychosis. Both genetic analysis and EEG recordings point to deficiencies in the cholinergic system. We then compared performance in visual backward masking with other tests. Surprisingly, performance in most tests did not correlate with each other. Conclusions: Our results suggest that each endophenotype is sensitive to different abnormal mechanisms. Schizophrenia is much more complex than previously thought. Heterogeneity can be best attacked by the combined investigation of sensitive endophenotypes.

2019

Neuromodulation of neocortical microcircuitry: a multi-scale framework to model the effects of cholinergic release

Cristina Colangelo

EPFL2022