neurotransmitter

What are the two components of chemical signaling?

A molecular signal (neurotransmitter) and a receptor molecule.

What are the main types of neurotransmitters?

Acetylcholine, Biogenic amines, and Amino acids.

What are the two main types of neurotransmitter receptors?

Ionotropic (ligand-gated channels) and Metabotropic (G-protein-coupled receptors).

How do ionotropic receptors function?

They are ligand-gated ion channels composed of 4-5 subunits and mediate rapid postsynaptic effects.

Name examples of ionotropic receptors.

NMDA, AMPA/Kainate, nicotinic AChR, 5-HT3, GABAA, Glycine, Purinergic receptors.

How do metabotropic receptors function?

They are GPCRs that modulate ion channels or other intracellular processes.

What are key structural features of GPCRs?

Monomeric proteins with 7 transmembrane domains; G-proteins bind to loop between domains V and VI and C-terminus.

Describe the structure of the nicotinic acetylcholine receptor (nAChR).

Consists of 5 subunits; muscle: αα:β:γ:δ; neuron: ααα:ββ; α-subunits bind ACh.

How is acetylcholine synthesized?

From acetyl coenzyme A and choline via enzyme choline acetyltransferase (ChAT).

What happens to ACh after it is released?

It is broken down by acetylcholinesterase into acetate and choline.

What is Myasthenia Gravis?

An autoimmune disorder where antibodies block AChRs, causing muscle fatigue and reduced EPP.

How is Myasthenia Gravis treated?

With reversible acetylcholinesterase inhibitors like neostigmine.

What is the danger of irreversible AChE inhibitors like nerve gases?

They cause overstimulation leading to neuromuscular paralysis and respiratory failure.

How is poisoning from irreversible AChE inhibitors treated?

With atropine (muscarinic antagonist) and pralidoxime (restores AChE function).

What is the major excitatory neurotransmitter in the brain?

Glutamate.

How is glutamate synthesized?

From glutamine via enzyme glutaminase.

Name the ionotropic glutamate receptors.

NMDA, AMPA, Kainate.

What is unique about NMDA receptors?

Require depolarization to relieve Mg2+ block and glycine as a co-agonist.

What role do NMDA receptors play in synaptic plasticity?

Ca2+ influx leads to AMPA-R phosphorylation and gene expression changes.

What are the groups of metabotropic glutamate receptors (mGluRs)?

Group I (excitatory), Group II and III (inhibitory).

What is the major inhibitory neurotransmitter in the brain?

GABA.

How is GABA synthesized?

From glutamate via glutamate decarboxylase (GAD).

What are the types of GABA receptors?

Ionotropic (GABAA, GABAC) and Metabotropic (GABAB).

How do benzodiazepines and barbiturates affect GABAA receptors?

Benzodiazepines increase frequency; barbiturates increase duration of Cl- channel opening.

How does synaptic inhibition work?

Opening of Cl- channels causes hyperpolarization, reducing action potential firing.

Why is GABA excitatory in developing brains?

High intracellular Cl- makes ECl- more positive than AP threshold.

How do GABAB receptors function?

Open K+ channels and inhibit Ca2+ channels, leading to hyperpolarization.

What is added in the definition of chemical signaling in Part II?

A target molecule (ion channel) altered to cause electrical response in postsynaptic cell.

What are the three small-molecule neurotransmitter types?

Acetylcholine, Biogenic amines, and Amino acids.

What are the main catecholamines?

Dopamine, Noradrenaline (Norepinephrine), Adrenaline (Epinephrine).

Where are catecholamines released as hormones?

By the adrenal glands in response to stress or low blood sugar.

What is the role of catecholamines in the CNS?

Act as neuromodulators influencing effects of classical neurotransmitters.

What factors determine catecholamine effects in the CNS?

Brain area, receptor subtype, signaling pathway, postsynaptic cell type.

What is the rate-limiting enzyme for catecholamine synthesis?

Tyrosine hydroxylase.

What regulates tyrosine hydroxylase activity?

Upregulated by stress, caffeine, nicotine, morphine; downregulated by antidepressants.

What is notable about the number of catecholaminergic neurons?

Only ~500,000 in the brain but they connect to thousands of other neurons.

What functions is dopamine associated with?

Motor control (Parkinson), reward, addiction, schizophrenia.

What functions is norepinephrine associated with?

Attention, wakefulness, stress, pain inhibition, ADHD.

What functions is epinephrine associated with?

Hormone secretion regulation, stress, autonomic function.

How is Parkinson’s disease related to dopamine?

It involves loss of DA neurons leading to motor disorders.

What defines addiction in terms of brain circuitry?

Out-of-control use despite consequences; affects VTA to nucleus accumbens circuit.

What is drug dependence?

Adaptive state leading to withdrawal symptoms upon stopping drug use.

What is drug tolerance?

Diminished effect with same dose or need for higher dose.

What is drug sensitization?

Increased response after repeated administration.

What is the final common pathway in addiction?

Dopamine system; all addictive drugs increase DA release.

What does repeated drug use do to D2 receptors?

Down-regulates them, reducing the brain's pleasure response.

What is VMAT?

Vesicular monoamine transporter that loads DA into vesicles.

What is DAT?

Dopamine transporter involved in reuptake.

What enzymes degrade dopamine?

Monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT).

How do amphetamines affect dopamine?

Increase DA release and reverse DAT to flood synapse with DA.

How does cocaine affect dopamine?

Blocks DAT, prolonging DA presence in synapse.

What is the main reuptake transporter for norepinephrine?

NET (Norepinephrine Transporter).

What types of receptors do norepinephrine and epinephrine act on?

α- and β-adrenergic GPCRs.

What is serotonin’s precursor?

Tryptophan, an essential amino acid.

What functions is serotonin (5-HT) associated with?

Mood, sleep, depression, anxiety, schizophrenia.

What is SERT?

Serotonin transporter, blocked by SSRIs.

How is serotonin degraded?

By monoamine oxidase (MAO).

Which serotonin receptor is ionotropic?

5-HT3 receptor.

What are the main ways neurotransmitter action is terminated?

Reuptake, uptake by glia, enzymatic breakdown, passive diffusion.