cognitive science 17 the chemical brainpineda/cogs17/overheads... · 2010. 1. 29. · receptor...
TRANSCRIPT
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