COGNITIVE SCIENCE 17

The Chemical Brain

Part 1

Matt Schalles, Rev.

Neurotransmitters I

Graded Potentials

● Depolarization (EPSP)● Vm becomes more positive ● Na+ flows in, sometimes Ca++● Can lead to opening of voltage gated channels

● Hyperpolarization (IPSP)● Vm becomes more negative ● K+ efflux, or Cl- influx● Prevents opening of VG channels

3 Types of Ion Channels● Channels that transduce

● Ligand Gated (same as ionotropic receptors)– Found in dendrites, cell body, and axon terminal

● Mechanically Gated– Commonly found in sensory neurons

● Channels that propagate● Voltage Gated

– Found all throughout neuron membrane– Propagate post synaptic potentials and action potentials

Receptor Action

● Ionotropic (ligand gated receptor)● Opens ion channel in receptor itself● Ions produce either excitation or inhibition● Fast action

● Metabotropic (g-protein coupled receptor)● Sets off cascade of chemical events● Can lead to ion channel opening on another

protein● Can lead to other, long-term changes● Slower action

The Life Cycle of a Conventional NT

● Biosynthesis & Storage● Release● Receptor Action● Inactivation

Biosynthesis

Precursor(s) Transmitter

Enzyme(s)

Storage

● Synaptic vesicles made by Golgi apparatus in cell body

● Precursors, enzymes, and vesicles are transported from cell body down axon to terminal

● At terminal, NTs are synthesized and packaged into vesicles

● Filled vesicles dock onto proteins in terminal

Release

● Action potential opens channels for Ca++ to enter terminal membrane

● Vesicles to undock and move to membrane

● Vesicles fuse with membrane and empty transmitter into synapse (exocytosis)

Inactivation

Breakdown Products

Transmitter

Enz

yme(

s)

• Destruction • Reuptake• Diffusion

Axon Terminal Activity Regulation● Autoreceptors● Heteroreceptors● Retrograde Signals

PresynapticAutoreceptor=

PresynapticHeteroreceptors

Depolarization induced suppression of excitation

How do we know what we know?Loss of function

– Head trauma– electrical/chemical

lesion– Magnetic pulses– Genetic knockouts

Gain of function– Genetic knock-in– Magnetic/electrical

pulses– chemicals

● Tools for Observation● Tools for manipulation

Principles of Psychopharmacology● Psychotropics – drugs affecting perception,

mood, & behavior● Pharmacokinetics – absorption, distribution,

breakdown, & excretion of drugs● Pharmacodynamics – effect drug exerts

Pharmacokinetics – Absorption● Types of Administration

– Injection– Oral– Topical

● Measurements of drug concentration

– Blood plasma– microdialysis

Pharmacokinetics - Distribution● Properties affecting absorption

– ph – Lipid vs water solubility

● Impediments to drugs– Inactivating enzymes

● MAO in gut– Depot binding

● Blood albumin● Fat cells

● Blood Brain Barrier– Faster drugs get past this, the 'better' the high

How much is too much?

Therapeutic Index = ratio of Lethal Dose to Effective Dose

– High therapeutic index = relatively safe drug– Low means proceed w/ caution