Neuroscience Chapter on Receptors

Receptors

• Two basic types of receptors: ionotropic and metabotropic.
• Ionotropic receptors are ligand-gated ion channels that open when a neurotransmitter binds to them.
• Metabotropic receptors are G-protein-coupled receptors that trigger a cascade of intracellular signals.
• Receptor location determines its function: postsynaptic receptors receive signals from presynaptic neurons and presynaptic receptors, such as autoreceptors and heteroreceptors, regulate neurotransmitter release.

Receptor Types

• Ionotropic receptors:
  • Also known as ligand-gated ion channels.
  • Can be excitatory (depolarizing), causing EPSPs, or inhibitory (hyperpolarizing), causing IPSPs.
  • Fast and transient effects.
• Metabotropic receptors:
  • Also known as G-protein-coupled receptors.
  • Modulate cellular activity and signal transduction.
  • Slow and longer-lasting effects.
  • Often lead to signal cascades within the cell.

Neurotransmitter Clean-up

• Three main types of neurotransmitter clean-up:
  • Diffusion: Neurotransmitters diffuse away from the synapse.
  • Enzymatic degradation: Enzymes break down neurotransmitters.
  • Re-uptake: Neurotransmitters are reabsorbed by presynaptic neurons or astrocytes.

Drug Types

• Agonists: Drugs that mimic the effects of neurotransmitters by binding to and activating their receptors.
• Antagonists: Drugs that block the effects of neurotransmitters by binding to their receptors without activating them.
• More complex drug action: These can include transporter blockers, reuptake inhibitors, and enzyme inhibitors.

Major Groups of Neurotransmitters

• Amino acid neurotransmitters:
  • Glutamate: Primary excitatory neurotransmitter.
    • Ionotropic receptors: AMPAR, NMDAR, Kainate receptor.
    • Metabotropic receptors: mGluR 1-8.
  • GABA: Primary inhibitory neurotransmitter.
    • Ionotropic and metabotropic receptors.
• Monoamine neurotransmitters:
  • Dopamine:
    • Involved in motivation, movement, learning, and arousal.
    • Projects from the substantia nigra pars compacta and ventral tegmental area (VTA) to various brain regions.
    • Five receptor subtypes, all metabotropic.
    • Not the "pleasure molecule."
  • Norepinephrine:
    • Both a hormone and neurotransmitter.
    • Involved in wakefulness, arousal, and memory enhancement.
    • Originates in the locus coeruleus.
    • Two main receptor types (⍺1-2, β1-3) with subtypes.
    • Plays a role in heterosynaptic facilitation.
  • Serotonin:
    • Involved in mood, sleep, and cognition.
    • Originates in the raphe nuclei.
    • 15 receptor subtypes, almost all metabotropic.
    • Not simply a "mood molecule."
• Other small neurotransmitters:
  • Acetylcholine:
    • The first discovered neurotransmitter.
    • Involved in muscle activation and cognitive functions.
    • Found at the neuromuscular junction and in the basal forebrain.
  • Endocannabinoids:
    • Two neurotransmitters: anandamide and 2-AG.
    • Involved in pain, appetite, and mood regulation.
    • Two receptor subtypes, both GPCRs.
    • Exhibit retrograde transmission.
  • Adenosine:
    • Produced from ATP.
    • Involved in sleep, wakefulness, and energy regulation.
    • Caffeine is an adenosine receptor antagonist.
• Large molecule neurotransmitters:
  • Endogenous opioids:
    • Also known as endorphins.
    • Giant peptide neurotransmitters.
    • Involved in pain perception, reward, and stress response.
    • Mimicked by exogenous opioids (e.g., heroin).

Drugs and their Impact on Neurotransmitter Systems

• Glutamate:
  • Glutamate antagonists include barbiturates, nitrous oxide, ketamine, and ethanol.
• GABA:
  • GABA agonists include benzodiazepines, ethanol, chloroform, and ether.
• Dopamine:
  • Addictive drugs directly or indirectly increase dopamine transmission.
• Norepinephrine:
  • Propranolol is a norepinephrine receptor antagonist (beta blocker).
• Serotonin:
  • SSRIs, like Prozac, are serotonin reuptake inhibitors.
  • Hallucinogens like LSD, DMT, and psilocybin are serotonin receptor agonists.
• Acetylcholine:
  • Nicotine is an acetylcholine receptor agonist.
• Endocannabinoids:
  • THC is a cannabinoid receptor agonist.
  • CBD effects are less clear.
• Adenosine:
  • Caffeine and theophylline are adenosine receptor antagonists.
• Endogenous opioids:
  • Fentanyl and naloxone are exogenous opioids.

Explore the fascinating world of receptors in neuroscience! This quiz covers two primary types of receptors: ionotropic and metabotropic, focusing on their functions, mechanisms, and effects on neuronal signaling. Test your understanding of how different receptors affect neurotransmitter release and cellular activity.