2020-09-30 09:44:21

Prelude (01:57)

Announcements

  • Quiz 2 next Thursday
  • Blog post 1 (of 3) due next Thursday

Today’s Topics

  • Warm-up
  • Neurotransmitters
  • Hormones

Warm-up

The presynaptic influx of which ion triggers the release of neurotransmitters from the axon terminal?

  • Na+
  • K+
  • Ca++
  • Cl-

The presynaptic influx of which ion triggers the release of neurotransmitters from the axon terminal?

  • Na+
  • K+
  • Ca++
  • Cl-

This type of postsynaptic receptor does NOT contain its own ion channel.

  • Ionotropic
  • Metabotropic
  • Ligand-gated

This type of postsynaptic receptor does NOT contain its own ion channel.

  • Ionotropic
  • Metabotropic
  • Ligand-gated

Which neurotransmitter is released at the largest number of synapses in the CNS?

  • Glutamate
  • GABA
  • Acetylcholine
  • Dopamine

Which neurotransmitter is released at the largest number of synapses in the CNS?

  • Glutamate
  • GABA
  • Acetylcholine
  • Dopamine

More on neurotransmitters

Monoamine neurotransmitters

Family Neurotansmitter
Monoamines Dopamine (DA)
Norepinephrine (NE)/Noradrenaline (NAd)
Epinephrine (Epi)/Adrenaline (Ad)
Serotonin (5-HT)
Melatonin
Histamine

Monoamine Song

Monoamine Song

Monoamines, do-do do do-do
Monoamines, do do do-do
Monoamines, do do do do-do do do-do do do-do do do do do-do do

Monoamine Song

Monoamines, do-pa-mine is one
Monoamines, norepi, too
Monoamines, sero-tonin e-pinephrine, dop-a- mine, nor-epinephrine, melatonin, whoo!

Monoamine Song

Monoamines, mod-u-late neurons
Monoamines, throughout the brain
Monoamines, keep people happy, brains snappy, not sleepy, not sappy, do-do do-do do-do do

Monoamine neurotransmitters

Family Neurotansmitter
Monoamines Dopamine (DA)
Norepinephrine (NE)/Noradrenaline (NAd)
Epinephrine (Epi)/Adrenaline (Ad)
Serotonin (5-HT)
Melatonin
Histamine

Dopamine (DA)

  • Released by two pathways that originate in the midbrain tegmentum
    • Substantia nigra -> striatum, meso-striatal projection
    • Ventral tegmental area (VTA) -> nucleus accumbens, ventral striatum, hippocampus, amygdala, cortex; meso-limbo-cortical projection

DA pathways

DA Disruption linked to

  • Parkinson’s Disease (mesostriatal)
    • DA agonists treat (agonists facilitate/increase transmission)
  • ADHD (mesolimbocortical)
  • Schizophrenia (mesolimbocortical)
    • DA antagonists treat
  • Addiction (mesolimbocortical)

DA Inactivated by

Dopamine receptors

Type Receptor Comments
Metabotropic D1-like (D1 and D5) more prevalent
D2-like (D2, D3, D4) target of many antipsychotics (drugs that treat schizophrenia symptoms)

Norepinephrine (NE)

  • Role in arousal, mood, eating, sexual behavior
  • Released by

Locus coeruleus

Sympathetic Nervous System

NE and monoamine oxidase

  • Monoamine oxidase inactivates monoamines in neurons, astrocytes
  • Monoamine oxidase inhibitors (MAOIs) increase NE, DA
    • Inhibiting inactivation ~ -(-1) = + 1
  • Treatment for depression, but side effects (dry mouth, nausea, headache, dizziness)

NE Anatomy

NE receptors

Type Receptor Comments
Metabotropic \(\alpha\) (1,2) antagonists treat anxiety, panic
\(\beta\) (1,2,3) ‘beta blockers’ in cardiac disease

Serotonin (5-HT)

  • Released by raphe nuclei in brainstem
  • Role in mood, sleep, eating, pain, nausea, cognition, memory
  • Modulates release of other NTs
  • Most of body’s 5-HT regulates digestion
    • Enteric nervous system

5-HT anatomy

5-HT receptors

  • Seven families (5-HT 1-7) with 14 types
  • All but one metabotropic

5-HT clinical significance

  • Ecstasy (MDMA) disturbs serotonin
  • So does LSD
  • Fluoxetine (Prozac)
    • Selective Serotonin Reuptake Inhibitor (SSRI)
    • Inhibits reuptake -> increases extracellular concentration
    • Treats depression, panic, eating disorders, others

5-HT clinical significance

  • 5-HT3 receptor antagonists are anti-mimetics used in treating nausea

Melatonin

  • Hormone released by pineal gland into bloodstream
  • Concentrations vary over the day, peak near bedtime
  • Release regulated by inputs from hypothalamus

Pineal gland

Histamine

  • In brain, released by hypothalamus, projects to whole brain
    • Metabotropic receptors
    • Role in arousal/sleep regulation
  • In body, part of immune response

Histamine

Other NTs

  • Gases
    • Nitric Oxide (NO), carbon monoxide (CO)
  • Neuropeptides
    • Substance P and endorphins (endogenous morphine-like compounds) have role in pain
    • Orexin/hypocretin, project from lateral hypothalamus across brain, regulate appetite, arousal

Other NTs

  • Neuropeptides (continued)
    • Cholecystokinin (CCK) stimulates digestion
    • Oxytocin and vasopressin released by posterior hypothalamus onto posterior pituitary, regulate social behavior

Non-chemical communication between neurons

  • Gap junctions
  • Electrical coupling
  • Connect cytoplasm directly
  • Fast, but fixed, hard to modulate
  • Examples, retina, cardiac muscle

Gap junctions

Ways to think about synaptic communication

  • Specificity: point-to-point vs. broadcast
  • Direct (immediate) action vs. (delayed, prolonged) modulatory
  • Agonists vs. antagonists

Agonists vs. Antagonists

  • Agonists
    • bind to receptor
    • mimic action of endogenous chemical
  • Antagonists
    • bind to receptor
    • block/impede action of endogenous chemical

Valium is a GABA-A receptor agonist. This means:

  • It decreases inhibition
  • It activates a metabotropic Cl- channel
  • It facilitates/increases inhibition
  • It blocks an ionotropic channel

Valium is a GABA-A receptor agonist. This means:

  1. It decreases inhibition
  2. It activates a metabotropic Cl- channel
  3. It facilitates/increases inhibition
  4. It blocks an ionotropic channel

Next time…

  • Hormones

References