• Neurochemistry
  • How neurons talk to one another
• Synaptic communication
• Neurotransmitters

• Soma receives input from dendrites
• Axon hillock sums/integrates
• If sum > threshold, AP "fires"

• Rapid change in voltage triggers neurotransmitter (NT) release
• Voltage-gated calcium Ca++ channels open
• Ca++ causes synaptic vesicles to bind with presynaptic membrane, merge, exocytosis

• NTs diffuse across synaptic cleft
• NTs bind with receptors on postsynaptic membrane
• Receptors respond
• NTs unbind, are inactivated

• Electrostatic force pulls them
• Force of diffusion

• Electrostatic force pulls them
• Force of diffusion

• Ligand-gated ion channels
• Ionotropic (receptor + ion channel)
  • Ligand-gated
  • Open/close channel
  • Faster, but short-acting effects

• Metabotropic (receptor only)
  • Trigger 2nd messengers
  • G-proteins
  • Open/close adjacent channels, change metabolism
  • Slower, but longer lasting effects

• Small voltage changes
• Amplitude scales with # of receptors activated
  • Dendrites usually lack voltage gated Na+ channels
• Excitatory PSPs (EPSPs)
  • Depolarize neuron (make more +)
• Inhibitory (IPSPs)
  • Hyperpolarize neuron (make more -)

• Buffering
  • e.g., glutamate into astrocytes (Anderson & Swanson, 2000)
• Reuptake via transporters
  • molecules in membrane that move NTs inside
  • e.g., serotonin via serotonin transporter (SERT)
• Enzymatic degradation
  • e.g., acetylcholinesterase (AChE) degrades acetylcholine (ACh)

• Why must NTs be inactivated?

• Why must NTs be inactivated?
  • Keeps messages discrete, localized in time and space
  • Maximizes concentration gradient

• Excitatory PSP, Na+ flows in
• Excitatory PSP, Na+ flows out
• Inhibitory PSP, Na+ flows in
• Inhibitory PSP, Na+ flows out

• Excitatory PSP, Na+ flows in
• Excitatory PSP, Na+ flows out
• Inhibitory PSP, Na+ flows in
• Inhibitory PSP, Na+ flows out

Remember [Cl-out]>>[Cl-in]

• Excitatory PSP, Cl- flows in
• Excitatory PSP, Cl- flows out
• Inhibitory PSP, Cl- flows in
• Inhibitory PSP, Cl- flows out

Remember [Cl-out]>>[Cl-in]

• Excitatory PSP, Cl- flows in
• Excitatory PSP, Cl- flows out
• Inhibitory PSP, Cl- flows in
• Inhibitory PSP, Cl- flows out

• dendrites
  • usually excitatory
• cell bodies
  • usually inhibitory
• axons
  • usually modulatory (change p(fire))

• Primary excitatory NT in CNS
• Role in learning (via NMDA)
• Receptors on neurons and glia (astrocytes and oligodendrocytes)
• Linked to umami (savory) taste sensation (think monosodium glutamate or MSG)
• Dysregulation in schizophrenia? (Javitt, 2010)

• Primary inhibitory NT in CNS
• Excitatory in developing CNS, [Cl-] in >> [Cl-] out
• Binding sites for benzodiazepines (e.g., Valium), barbiturates, ethanol, etc.

• Aspartate
  • Like Glu, stimulates NMDA receptor
• Glycine
  • Spinal cord interneurons

• Primary excitatory NT of CNS output
• Somatic nervous system (motor neuron -> neuromuscular junction)
• Autonomic nervous system
  • Sympathetic branch: preganglionic neuron
  • Parasympathetic branch: pre/postganglionic

• aka, nightshade or belladonna

• Point-to-point
  • One sender, small number of recipients
  • Glu, GABA
• Broadcast
  • One sender, widespread recipients
  • DA, NE, 5-HT, melatonin, histamine
• Need to know
  • NT, where projecting, type of receptor to predict function

• Released by
  • Substantia nigra -> striatum, meso-striatal projection
  • Ventral tegmental area (VTA) -> nucleus accumbens, ventral striatum, hippocampus, amygdala, cortex; meso-limbo-cortical projection

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

• Dopamine transporter (DAT) and chemical breakdown

http://www.scholarpedia.org/article/Dopamine_anatomy#Dopamine_receptors

• Released by
  • locus coeruleus in pons
  • postganglionic sympathetic neurons onto target tissues
• Role in arousal, mood, eating, sexual behavior
• Monoamine oxidase inhibitors (MAOIs)
  • inactivate monoamines in neurons, astrocytes
  • MAOIs increase NE, DA
  • Treatment for depression

• 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

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

• Ecstasy (MDMA) disturbs serotonin
• So does LSD
• Fluoxetine (Prozac)
  • Selective Serotonin Reuptake Inhibitor (SSRI)
  • Treats depression, panic, eating disorders, others
• 5-HT3 receptor antagonists are anti-mimetics used in treating nausea

• Released by pineal gland

• Released by hypothalamus, projects to whole brain
• \(H_1\)-\(H_4\) Metabotropic receptors, one ionotropic type in thal/hypothal
• Role in arousal/sleep regulation
• In body, part of immune/inflammatory response

https://en.wikipedia.org/wiki/Mah_Nà_Mah_Nà

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

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

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

• 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, regulates appetite, arousal
  • Cholecystokinin (CCK) stimulates digestion
• Purines
  • Adenosine (inhibited by caffeine)
• Others
  • Anandamide (activates endogenous cannabinoid receptors)