As the first chemical messenger ever identified in the history of neuroscience, acetylcholine bridges the gap between electrical impulses and biological action across both the central and peripheral nervous systems. From coordinating microscopic muscle contractions to orchestrating higher-order cognitive networks responsible for memory encoding, attention, and sensory gating, this ubiquitous molecule governs essential physiological faculties. Understanding acetylcholine’s synthesis, receptor pharmacology, and systemic degradation provides foundational insights into neurological medicine, evolutionary biology, and human consciousness.
Acetylcholine (ACh)
1. Concise Definition
Acetylcholine (commonly abbreviated as ACh) is an organic polyatomic cation and ester of acetic acid and choline that functions as a primary neurotransmitter in humans and numerous other animal taxa. Synthesized in presynaptic terminals, it mediates chemical transmission at the neuromuscular junction, within autonomic ganglia, at parasympathetic target neuroeffector sites, and across widespread neuromodulatory circuits within the central nervous system.
Functioning across both rapid millisecond-scale electrical transmissions and prolonged metabotropic intracellular signaling, acetylcholine operates via two distinct receptor classes: ionotropic nicotinic acetylcholine receptors and metabotropic muscarinic acetylcholine receptors. In the peripheral nervous system, acetylcholine is indispensable for both voluntary somatic motor control and involuntary homeostatic regulation. Centrally, cholinergic projections ascending from basal forebrain and brainstem nuclei modulate cortical arousal, synaptic plasticity, selective attention, and the structural stabilization of memory traces.
2. Etymology & Linguistic Origin
The term acetylcholine is an organic chemical compound name constructed from the chemical radical “acetyl” and the quaternary ammonium base “choline.” The word “acetyl” derives historically from the Latin acetum (meaning vinegar or sour wine), reflecting its direct structural relation to acetic acid. The suffix “-yl” stems from the Greek hyle (υλη), traditionally translated in scientific nomenclature as “matter,” “substance,” or “elemental matrix.”
The root “choline” was coined in the nineteenth century from the Greek chole (χολη), signifying “bile,” due to its original biochemical isolation from bovine bile by German chemist Adolph Strecker in 1862. When chemically acetylated via an ester linkage, the resulting compound yielded the designation acetylcholine, cataloging both its chemical constituents and its synthesis from choline and activated acetate precursors.
3. Pronunciation & Grammatical Form
Pronunciation: Phonetically transcribed in the International Phonetic Alphabet (IPA) as /æ⋅sε⋅tæl⋅"ko&Section;⋅li&Section;n/ or /æ⋅s&i;⋅t⋅æl⋅"ko&Section;⋅li&Section;n/.
Grammatical Form: Acetylcholine functions grammatically as an uncountable mass noun. In medical and biochemical literature, it is universally abbreviated as “ACh.” Derivative adjectival and functional forms include cholinergic (pertaining to nerve fibers, receptors, or physiological pathways mediated by or responding to acetylcholine), acetylcholinesterase (the hydrolytic degradation enzyme, abbreviated AChE), and anticholinergic (agents or clinical states characterized by the antagonism or suppression of acetylcholine-mediated transmission).
4. Detailed Conceptual Explanation
At its biochemical foundation, acetylcholine is an ester synthesized in the cytoplasm of cholinergic nerve terminals from its two direct precursors: choline and acetyl-coenzyme A (acetyl-CoA). Choline is transported into the intracellular compartment of the neuron from extracellular fluid via a specialized, rate-limiting, sodium-dependent high-affinity choline transporter (CHT1). Simultaneously, acetyl-CoA is generated within neuronal mitochondria through the metabolism of pyruvate. The enzymatic transfer of the acetyl moiety from acetyl-CoA to choline is catalyzed by the cytoplasmic enzyme choline acetyltransferase (ChAT).
Following enzymatic synthesis, acetylcholine is actively packaged into synaptic vesicles by the vesicular acetylcholine transporter (VAChT), a proton-antiporter that leverages an electrochemical gradient established by vacuolar ATPases. Once packed within synaptic vesicles, acetylcholine remains stored until an invading action potential depolarizes the presynaptic terminal, triggering the opening of voltage-gated calcium channels. The influx of calcium ions engages SNARE proteins (including synaptobrevin, syntaxin, and SNAP-25), prompting the fusion of vesicular membranes with the presynaptic active zone and releasing quantal bursts of acetylcholine into the synaptic cleft via exocytosis.
Unlike many monoaminergic neurotransmitters whose synaptic actions are principally terminated by presynaptic reuptake transporters, acetylcholine is uniquely and rapidly eliminated through enzymatic hydrolysis. Within the synaptic cleft, the anchored enzyme acetylcholinesterase (AChE) hydrolyzes acetylcholine at an extraordinary catalytic velocity—approaching diffusion limits—into acetate and free choline. This rapid catalytic cleavage ensures millisecond temporal precision at somatic synapses and prevents persistent, toxic receptor desensitization. The liberated choline is subsequently taken back up by the presynaptic terminal through CHT1 to fuel subsequent rounds of neurotransmitter synthesis.
The target actions of acetylcholine depend entirely on the class of receptors expressed on the postsynaptic or presynaptic membrane. Nicotinic receptors (nAChRs) are ligand-gated, pentameric ion channels that mediate fast, excitatory cation influx (primarily sodium and calcium), producing rapid depolarization. Conversely, muscarinic receptors (mAChRs) are seven-transmembrane G-protein-coupled receptors (GPCRs) divided into five subtypes (M1 through M5). Odd-numbered subtypes (M1, M3, M5) couple through Gq/11 proteins to stimulate phospholipase C and mobilize intracellular calcium, whereas even-numbered subtypes (M2, M4) couple to Gi/o proteins to inhibit adenylyl cyclase and modulate potassium conductances. Through this dual receptor machinery, acetylcholine coordinates both instantaneous kinetic signaling and sustained modulatory neurocomputations.
5. Historical Development
The timeline of acetylcholine’s identification reflects the birth of modern neuropharmacology and synaptic physiology during the late nineteenth and early twentieth centuries:
- 1867: German chemist Adolf von Baeyer first synthesized acetylcholine in a laboratory setting as a novel chemical compound, long before its endogenous biological existence or neurotransmitter function was recognized.
- 1906: British physiologist Reid Hunt demonstrated that acetylcholine exhibited extraordinary physiological potency, lowering arterial blood pressure and slowing cardiac contractions at doses far lower than adrenaline or related compounds.
- 1914: Sir Henry Hallett Dale published seminal work classifying the distinct pharmacological actions of acetylcholine into two separate biological categories: “nicotinic” actions (resembling the physiological effects of nicotine) and “muscarinic” actions (resembling those of the fungal alkaloid muscarine).
- 1921: Austrian pharmacologist Otto Loewi performed his legendary nocturnal dual-heart perfusion experiment on isolated frog hearts (Rana esculenta). By stimulating the vagus nerve of one heart and transferring the surrounding physiological fluid to a second denervated heart, Loewi demonstrated that a chemical substance—which he initially termed Vagusstoff (“vagus substance”)—slowed cardiac rate, establishing the fundamental principle of chemical synaptic transmission.
- 1926–1936: Otto Loewi and Henry Dale conclusively proved that Vagusstoff was chemically identical to acetylcholine. Dale and his associates subsequently demonstrated that acetylcholine is liberated at somatic motor nerve terminals, acting as the physiological transmitter of the neuromuscular junction. Loewi and Dale were jointly awarded the Nobel Prize in Physiology or Medicine in 1936.
- 1970s–1980s: The cholinergic hypothesis of geriatric memory dysfunction and Alzheimer’s disease emerged following post-mortem discoveries by Peter Davies and colleagues revealing substantial reductions in choline acetyltransferase activity and severe degeneration of cholinergic neurons within the basal forebrain of affected patients.
6. Theoretical Foundations
The theoretical framework surrounding acetylcholine has evolved across multiple domains of physiology, neurocomputation, and systemic neuroscience. In peripheral motor physiology, acetylcholine exemplifies Sir Bernard Katz’s quantal hypothesis of neurotransmission. According to this framework, neurotransmitters are stored and discharged in uniform packages known as quanta, corresponding to the content of individual synaptic vesicles. Miniature end-plate potentials (mEPPs) reflect the spontaneous baseline exocytosis of single quanta of acetylcholine, whereas full action potential-evoked end-plate potentials represent the synchronized release of hundreds of quanta, reliably surpassing the electrical threshold for muscle action potentials.
In cognitive neuroscience, the cholinergic system is central to the theoretical model of neuromodulation proposed by Michael Hasselmo and colleagues. This computational framework models acetylcholine as a dynamic regulator that sets the operational tone between sensory-driven learning and internal memory retrieval. Elevated cholinergic tone in the hippocampus and neocortex suppresses recurrent collateral excitatory transmission while simultaneously enhancing feedforward sensory inputs and facilitating long-term potentiation (LTP). Consequently, high acetylcholine levels bias neural networks toward encoding novel sensory experiences without interference from previously established associative memories, whereas low acetylcholine states (such as during slow-wave sleep) permit unhindered consolidation and transfer of hippocampal representations to neocortical ensembles.
Furthermore, in computational models of attention and predictive coding developed by Karl Friston and Angela Yu, acetylcholine signaling acts as a biological parameter encoding “expected uncertainty.” According to this formulation, cholinergic bursts within cortical layers inform cognitive systems that current predictive models of the environment are unreliable due to known environmental noise. This signal boosts perceptual plasticity, upregulates sensory processing, and facilitates the rapid revision of behavioral strategies in changing operational environments.
7. Key Components, Types & Dimensions
The cholinergic system comprises distinct molecular, anatomical, and functional elements distributed throughout biological tissues:
- Nicotinic Acetylcholine Receptors (nAChRs): Pentameric ligand-gated ion channels composed of combinations of alpha (α2–α10) and beta (β2–β4) subunits, as well as muscle-specific gamma (γ), delta (δ), and epsilon (ε) subunits. Muscle-type receptors ((α1)2β1δγ or (α1)2β1δε) govern the neuromuscular junction, whereas neuronal types (such as homomeric α7 or heteromeric α4β2) govern autonomic ganglia and modulate central neuronal excitability and dopamine release.
- Muscarinic Acetylcholine Receptors (mAChRs): A family of five G-protein-coupled receptors. Subtypes M1, M3, and M5 couple via Gq/11 proteins to activate the inositol trisphosphate (IP3) and diacylglycerol (DAG) cascades, increasing intracellular calcium. Subtypes M2 and M4 couple via Gi/o proteins to suppress adenylyl cyclase, downregulate cyclic adenosine monophosphate (cAMP), and activate inwardly rectifying potassium channels (GIRK), typically exerting hyperpolarizing, inhibitory effects.
- Basal Forebrain Cholinergic Complex: A major central cholinergic pathway encompassing the medial septal nucleus, the vertical and horizontal limbs of the diagonal band of Broca, and the nucleus basalis of Meynert. These neurons send expansive topographical projections throughout the hippocampus, amygdala, and neocortex, driving arousal, working memory, and sustained attention.
- Pontomesencephalic Cholinergic Complex: Comprising the pedunculopontine tegmental nucleus (PPTg) and the laterodorsal tegmental nucleus (LDTg), this brainstem system projects to the thalamus, striatum, and reticular formation, modulating sleep architecture (particularly REM sleep initiation), sensorimotor gating, and locomotion.
- Striatal Cholinergic Interneurons: Large, tonically active neurons (TANs) comprising approximately 1–2% of striatal cellularity that project dense local arborizations. They coordinate bidirectional crosstalk with dopaminergic afferents to regulate habit formation, motor pattern selection, and reinforcement learning.
- Autonomic Cholinergic Circuits: Acetylcholine serves universally as the primary neurotransmitter for preganglionic fibers in both the sympathetic and parasympathetic divisions of the autonomic nervous system. Additionally, it serves as the terminal neurotransmitter for postganglionic parasympathetic fibers, acting upon cardiac pacemaker cells, smooth muscle, and secretory glands.
8. Examples & Illustrative Cases
To grasp the multifaceted operations of acetylcholine in everyday physiology and pathological disruption, consider the following real-world clinical and behavioral scenarios:
Case Illustration 1: The Muscarinic Autonomic Cascade. Following a substantial meal, parasympathetic efferent fibers traveling within the vagus nerve release acetylcholine onto muscarinic M2 receptors embedded within the sinoatrial and atrioventricular nodes of the myocardium, opening inward-rectifying potassium channels and slowing the resting heart rate. Concurrently, cholinergic terminals release acetylcholine onto M3 receptors located on gastrointestinal smooth muscle and exocrine secretory cells. This engagement initiates intracellular calcium release, accelerating gastrointestinal peristalsis and stimulating digestive enzyme secretion—illustrating acetylcholine’s role in governing “rest-and-digest” physiology.
Case Illustration 2: Autoimmune Interruption at the Motor Endplate. A 34-year-old patient presents with fluctuating bilateral ptosis (drooping eyelids), diplopia (double vision), and profound proximal muscle weakness that worsens during continuous physical exertion and resolves partially following rest. Serum antibody assays confirm the presence of circulating autoantibodies directed against muscle-type nicotinic acetylcholine receptors. In this classic manifestation of myasthenia gravis, antibody binding drives receptor internalization, complement-mediated destruction of postsynaptic junctional folds, and functional blockade of ACh binding sites. Administering a reversible acetylcholinesterase inhibitor (such as pyridostigmine) increases the concentration and persistence of endogenous acetylcholine within the synaptic cleft, prolonging receptor interaction and transiently restoring muscle contraction force.
Case Illustration 3: Acute Anticholinergic Poisoning. An individual inadvertently ingests plants containing high concentrations of belladonna alkaloids, such as Atropa belladonna or Datura stramonium, rich in the competitive muscarinic antagonist atropine. Within hours, the competitive displacement of acetylcholine causes severe systemic parasympathetic shutdown and central delirium. Clinically described by the classical medical mnemonic: “blind as a bat” (mydriasis and cycloplegia from blocked pupillary constriction), “mad as a hatter” (acute central cholinergic delirium and visual hallucinations), “red as a beet” (cutaneous vasodilation to vent trapped body heat), “hot as a hare” (anhidrosis and hyperthermia due to blocked sweat gland innervation), and “dry as a bone” (profound xerostomia from salivary inhibition).
9. Measurement & Assessment
Evaluating acetylcholine synthesis, release, and receptor occupancy requires specialized neurochemical, electrophysiological, and neuroimaging modalities tailored to both preclinical models and clinical diagnostics:
In Vivo Neurochemical Sampling: In animal studies, extracellular acetylcholine concentrations are measured using intracranial microdialysis coupled with high-performance liquid chromatography (HPLC) or mass spectrometry. Due to rapid enzymatic hydrolysis by acetylcholinesterase, microdialysis perfusates typically incorporate trace concentrations of cholinesterase inhibitors (such as neostigmine) to preserve harvested acetylcholine molecules for quantitative quantification.
Amperometric Enzyme-Based Biosensors: For high-resolution, millisecond-level detection of dynamic cholinergic transients during behavioral tasks, researchers utilize microelectrode biosensors coated with acetylcholinesterase and choline oxidase. When acetylcholine encounters the sensor surface, AChE hydrolyzes it to choline, which choline oxidase subsequently converts to hydrogen peroxide (H2O2). The electrochemical oxidation of H2O2 at the electrode generates a measurable electrical current proportional to instantaneous neurotransmitter release.
Positron Emission Tomography (PET) and SPECT: In living humans, cholinergic pathways are mapped using specialized radioactive radiotracers. Radioligands targeting acetylcholinesterase (such as [11C]PMP or [11C]MP4A) measure regional enzyme kinetics, whereas ligands like [18F]FEOBV specifically bind the vesicular acetylcholine transporter (VAChT), serving as a surrogate marker of presynaptic terminal density across neurodegenerative conditions like Alzheimer’s and Parkinson’s diseases.
Electromyography (EMG): In clinical neurology, single-fiber electromyography (SFEMG) assesses neuromuscular transmission fidelity. Jitter—the variability in the time interval between action potentials of two muscle fibers belonging to the same motor unit—serves as an exquisitely sensitive physiological metric of acetylcholine receptor availability and miniature end-plate stability.
10. Applications & Practical Significance
The manipulation of cholinergic transmission represents one of the most widely used strategies in modern medicine, anesthesiology, toxicology, and ergonomics:
Dementia Therapeutics: The primary pharmacological approach for mild-to-moderate Alzheimer’s disease relies on centrally active, reversible acetylcholinesterase inhibitors, including donepezil, rivastigmine, and galantamine. By delaying the degradation of acetylcholine liberated by surviving basal forebrain projections, these agents provide modest symptomatic stabilization of cognitive scores and activities of daily living.
Surgical Anesthesia: Neuromuscular blocking agents are standard elements of general anesthesia during surgical procedures. Depolarizing agents (such as succinylcholine) bind nicotinic receptors and cause prolonged depolarization, rendering the endplate refractory to further stimulation. Non-depolarizing agents (such as rocuronium and vecuronium) competitively antagonize muscle nicotinic receptors, inducing complete skeletal muscle relaxation to facilitate endotracheal intubation and surgical access.
Ophthalmology and Autonomic Therapeutics: Muscarinic agonists (such as pilocarpine) are administered topically to induce miosis and contract the ciliary muscle, facilitating drainage of aqueous humor through the canal of Schlemm to reduce intraocular pressure in glaucoma. Conversely, muscarinic antagonists (such as tiotropium and ipratropium) act as inhaled bronchodilators, blocking airway smooth-muscle M3 receptors to manage chronic obstructive pulmonary disease (COPD) and asthma.
Toxicology and Chemical Defense: Irreversible organophosphate compounds—utilized in agricultural insecticides (e.g., malathion, chlorpyrifos) and chemical warfare nerve agents (e.g., sarin, VX, novichok)—covalently bind the serine hydroxyl group within the active site of acetylcholinesterase. The resulting accumulation of unhydrolyzed acetylcholine precipitates a cholinergic crisis, marked by profuse respiratory secretions, bronchospasm, profound bradycardia, flaccid paralysis of respiratory musculature, and death from asphyxiation. Emergency intervention requires rapid administration of muscarinic antagonists (atropine) and oxime-based acetylcholinesterase reactivators (such as pralidoxime, 2-PAM).
11. Research & Empirical Evidence
Decades of basic and translational research have established acetylcholine as an essential driver of synaptic plasticity, attention, and systemic homeostasis. Foundational work by Mark Bear and colleagues revealed that cholinergic activation is an absolute prerequisite for structural and functional ocular dominance plasticity within the primary visual cortex, illustrating that ACh confers permissive plasticity to mature neural circuits.
In behavioral neuroscience, optogenetic and chemogenetic studies led by researchers such as Zayd Khaliq and Adam Kepecs have revealed the precise temporal dynamics of basal forebrain cholinergic neurons during behavioral tasks. Rather than functioning solely as a diffuse, slow-acting arousal regulator, basal forebrain cholinergic neurons deliver fast, phasic signals to neocortical pyramidal neurons, arriving within tens of milliseconds of an unexpected sensory cue or reinforcement outcome. This burst transiently shifts local neocortical networks out of synchronized low-frequency oscillations into desynchronized high-frequency gamma rhythms, sharpening signal-to-noise ratios during high cognitive demand.
In human neurology, extensive autopsy and structural imaging investigations pioneered by Whitehouse and colleagues established that up to 90% of cholinergic neurons within the nucleus basalis of Meynert undergo neurodegeneration in advanced Alzheimer’s disease. Subsequent large-scale clinical trials have validated that while cholinesterase inhibitors do not arrest the underlying amyloid and tau cascades, they provide measurable improvements in global functional metrics by maximizing the physiological impact of remaining cholinergic transmission.
12. Cultural & Cross-Cultural Considerations
Human interaction with cholinergic neurobiology spans millennia through the traditional cultivation and use of naturally occurring botanical alkaloids across diverse cultural landscapes. Traditional societies recognized plants harboring potent cholinergic and anticholinergic compounds, incorporating them into spiritual rituals, therapeutic systems, and traditional hunting poisons.
In the Americas, indigenous populations cultivated Nicotiana rustica and Nicotiana tabacum, leveraging nicotine—the prototypical agonist of nicotinic acetylcholine receptors—for sacred ceremonial, diplomatic, and medicinal purposes. In the Mediterranean and European spheres, Solanaceae family plants containing muscarinic antagonists (such as Hyoscyamus niger [henbane], Mandragora officinarum [mandrake], and Atropa belladonna) were historically integrated into traditional herbalism, folklore, and surgical sedation mixtures (such as the medieval soporic sponge).
In traditional West African legal traditions, the Calabar bean (Physostigma venenosum) was historically employed as an “ordeal bean” in judicial trials. The active alkaloid within the bean, physostigmine, is a natural reversible acetylcholinesterase inhibitor. Individuals forced to ingest the poisonous bean experienced severe cholinergic toxicity; survival depended largely on whether rapid emetic responses occurred before fatal doses were absorbed, an outcome interpreted as evidence of guilt or innocence.
13. Criticisms, Debates & Limitations
Despite more than a century of scientific investigation, several controversies and conceptual limitations persist regarding acetylcholine’s therapeutic manipulation and theoretical models:
The Cholinergic Hypothesis of Alzheimer’s Disease: Although acetylcholinesterase inhibitors remain the front-line symptomatic treatment for Alzheimer’s disease, the original hypothesis that cholinergic depletion is the primary cause of dementia has faced significant criticism. Critics argue that cholinergic loss represents a downstream neurodegenerative event rather than the initial etiology, noting that cholinesterase inhibitors provide only modest, transient symptomatic improvements without altering long-term disease progression or preventing neurodegeneration.
Volume Transmission vs. Point-to-Point Synaptic Wiring: A longstanding debate centers on the structural mode of cholinergic communication within the central nervous system. Classic electron microscopy suggested that many cholinergic axonal varicosities lacked classical postsynaptic specializations, fostering the idea that acetylcholine operates predominantly through diffuse “volume transmission” via non-junctional ambient diffusion. However, subsequent high-resolution ultrastructural investigations have demonstrated that a significant proportion of central cholinergic synapses exhibit defined postsynaptic junctional structures, challenging the volume transmission model and indicating that acetylcholine acts through both precise, millisecond-scale wiring and broader paracrine neuromodulation.
The Cumulative Anticholinergic Burden: In modern geriatric pharmacotherapy, mounting evidence highlights the substantial risk of “anticholinergic cognitive burden.” Widespread medications—including tricyclic antidepressants, first-generation antihistamines, bladder antispasmodics, and antipsychotics—exhibit off-target competitive antagonism at central muscarinic receptors. Large-scale longitudinal epidemiological studies have linked prolonged cumulative use of these compounds to worsened cognitive decline, acute delirium, and an elevated long-term risk of developing incident dementia, prompting ongoing debates regarding medication management protocols for older adults.
14. Related Terms & Distinctions
To avoid conceptual confusion, acetylcholine must be distinguished from related neurochemicals, receptors, and enzymes within its metabolic pathway:
- Choline: An essential nutrient and quaternary ammonium alcohol that serves as the biological precursor to acetylcholine and phosphatidylcholine; unlike acetylcholine, unconjugated choline exhibits negligible affinity for nicotinic and muscarinic receptors under standard physiological concentrations.
- Acetylcholinesterase (AChE): The primary hydrolytic enzyme localized within synaptic clefts that cleaves acetylcholine into acetate and choline; it is the catalytic agent of degradation rather than a signaling molecule.
- Butyrylcholinesterase (BChE): A secondary, non-specific cholinesterase synthesized by the liver and present in serum and glial cells that hydrolyzes various choline esters, serving as an auxiliary metabolizing enzyme compared to the precise neurosynaptic actions of AChE.
- Nicotine: An exogenous plant-derived alkaloid that selectively activates nicotinic acetylcholine receptors, bypassing muscarinic systems entirely.
- Muscarine: A water-soluble toxin derived from mushrooms such as Amanita muscaria that selectively stimulates muscarinic acetylcholine receptors without activating nicotinic receptors at the neuromuscular junction.
- Norepinephrine: The primary neurotransmitter released by sympathetic postganglionic terminals; in peripheral autonomic signaling, norepinephrine mediates sympathetic actions (“fight-or-flight”), while acetylcholine mediates parasympathetic functions (“rest-and-digest”).
15. Key Takeaways
Acetylcholine occupies a central place in neurobiology as both a rapid transmitter of physical action and a master modulator of higher cognition. Synthesized by choline acetyltransferase from choline and acetyl-CoA, it acts upon two major receptor classes: rapid ionotropic nicotinic receptors and complex metabotropic muscarinic receptors. In the peripheral nervous system, it orchestrates skeletal motor movement and parasympathetic visceral regulation; in the central nervous system, projections ascending from the basal forebrain and brainstem shape cortical attention, synaptic plasticity, and memory formation. Rapidly cleared by acetylcholinesterase, its dysregulation underlies profound clinical conditions ranging from myasthenia gravis and acute toxidromes to the cognitive deficits of Alzheimer’s disease.
References
- Dale, H. H. (1914). The action of certain esters and ethers of choline, and their relation to muscarine. Journal of Pharmacology and Experimental Therapeutics, 6(2), 147–190.
- Davies, P., & Maloney, A. J. (1976). Selective loss of central cholinergic neurons in Alzheimer’s disease. The Lancet, 308(8000), 1403.
- Hasselmo, M. E. (2006). The role of acetylcholine in learning and memory as viewed on the basis of computational modeling. Neurobiology of Learning and Memory, 85(3), 269–285.
- Katz, B. (1969). The Release of Neural Transmitter Substances. Charles C Thomas Publisher.
- Loewi, O. (1921). Über humorale Übertragbarkeit der Herznervenwirkung. I. Mitteilung. Pflügers Archiv für die gesamte Physiologie des Menschen und der Tiere, 189(1), 239–242.
- Sarter, M., Parikh, V., & Howe, W. M. (2009). Phasic acetylcholine release and the volume transmission hypothesis: Time to move on. Nature Reviews Neuroscience, 10(5), 383–390.
- Whitehouse, P. J., Price, D. L., Struble, R. G., Clark, A. W., Coyle, J. T., & DeLong, M. R. (1982). Alzheimer’s disease and senile dementia: Loss of neurons in the basal forebrain. Science, 215(4537), 1237–1239.