Whole-brain modeling explains the context-dependent effects of cholinergic neuromodulation
Carlos Coronel-Oliveros1, Carsten Gießing2, Vicente Medel3
1Doctorado en Ciencias Mención Biofísica y Biología Computacional, Universidad de Valparaíso, Valparaíso, Chile; Latin American Health Brain Institute (BrainLat), Universidad Adolfo Ibáñez, Santiago, Chile; Centro Interdisciplinario de Neurociencia de Valparaíso (CINV), Universidad de Valparaíso, Valparaíso, Chile.
Neuroimage
|December 4, 2022
Summary
Nicotine enhances brain functional segregation, improving task performance. This effect, mediated by the cholinergic system, is context-dependent, aiding attentional tasks but not resting states.
Area of Science:
- Neuroscience
- Cognitive Science
- Computational Neuroscience
Background:
- Brain organization relies on integration and segregation principles.
- Neuromodulatory systems balance functional states.
- Cholinergic system's pro-segregation effects are increasingly recognized.
Purpose of the Study:
- Investigate cholinergic system's impact on brain functional connectivity.
- Examine nicotine's effects on functional connectivity and network topology.
- Explore causal mechanisms using computational modeling.
Main Methods:
- Empirical fMRI data analysis in healthy subjects (resting-state and attentional task).
- Whole-brain neural mass modeling with human connectome.
- Modeling nicotine's cellular effects by altering global coupling and local feedback inhibition.
Main Results:
- Nicotine increased functional segregation in both empirical and simulated data.
- Effects were context-dependent: present during attentional task, absent during rest.
- In-task performance correlated with functional segregation; regional α4β2 receptor density modulated nicotine's effects.
Conclusions:
- Cholinergic neuromodulation promotes functional segregation in a context-dependent manner.
- Enhanced segregation by nicotine supports performance in simple visual-attentional tasks.
- Links functional network topology to behavior and receptor distribution.
Related Concept Videos
01:30Indirect-Acting Cholinergic Agonists: Pharmacological Actions
749
Indirect-acting cholinergic agonists, also known as anticholinesterases, exert their pharmacological effects by enhancing cholinergic transmission in various body parts, including the neuromuscular junction, autonomic cholinergic synapses, and the brain.
At the neuromuscular junction, these agents work by inhibiting the breakdown of acetylcholine, allowing it to remain bound to the receptor and bind to nearby receptors. This process leads to repetitive firing of the endplate, causing muscle...
At the neuromuscular junction, these agents work by inhibiting the breakdown of acetylcholine, allowing it to remain bound to the receptor and bind to nearby receptors. This process leads to repetitive firing of the endplate, causing muscle...
749
01:23Cholinergic Neurons: Neurotransmission
3.2K
Cholinergic neurotransmission involves the synthesis and the release of acetylcholine (ACh) in order to transmit nerve impulses across the synapse. The process begins with the synthesis of acetyl CoA, a precursor for ACh, from ATP, acetate, and coenzyme A in the mitochondria. Choline, another vital precursor, is transported inside the neuron through choline transporters, including high-affinity choline transporter CHT1, low-affinity choline transporter CTL1, and lower-affinity choline...
3.2K
01:30Cognitive Enhancers: Cholinesterase Inhibitors and NMDA Receptor Antagonists
182
Cognitive enhancers, also known as "smart drugs," are substances used to enhance memory, mental alertness, and concentration. These can be natural or synthetic and improve cognition in conditions like Alzheimer's disease (AD) and other neurodegenerative diseases. Some common examples include caffeine, amphetamines, methylphenidate, modafinil, arecoline, donepezil, vortioxetine, and piracetam. These enhancers work on the principle of synaptic plasticity and altered circuit function.
182
01:28Cholinergic Antagonists: Pharmacological Actions
1.2K
Antimuscarinic drugs block muscarinic receptors in multiple systems, including the gut, eye, smooth muscles, respiratory tract, cardiovascular, and central nervous systems. They produce similar effects with varying selectivity depending on the specific agent and tissue. Here are the key pharmacological actions of antimuscarinics:
Gastrointestinal Effects: Antimuscarinics reduce gut contractions, increase gastric emptying, and slow intestinal transit. They partly inhibit gastric acid secretion...
Gastrointestinal Effects: Antimuscarinics reduce gut contractions, increase gastric emptying, and slow intestinal transit. They partly inhibit gastric acid secretion...
1.2K
01:18Indirect-Acting Cholinergic Agonists: Mechanism of Action
2.0K
Indirect-acting cholinergic agonists work by interacting with an enzyme called acetylcholinesterase (AChE) in the synaptic cleft. They can be reversible or irreversible inhibitors and have different effects on the enzyme.
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex,...
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex,...
2.0K
00:59Direct-Acting Cholinergic Agonists: Pharmacological Actions
1.5K
Direct-acting cholinergic agonists exert their pharmacological actions by mimicking the effects of acetylcholine on postsynaptic muscarinic receptors to generate parasympathetic responses. These agents elicit a range of physiological responses, including cardiovascular effects. For example, activation of muscarinic receptors induces bradycardia, decreased cardiac output, reduced peripheral resistance, and consequent hypotension. In the eye, stimulation of M3 receptors leads to smooth muscle...
1.5K