Neurotransmitters I

Neurotransmitters I

The Life Cycle of a Conventional NTBiosynthesis & StorageReleaseReceptor ActionInactivation

BiosynthesisPrecursor(s)

StorageSynaptic vesicles made by Golgi apparatus in cell bodyPrecursors, enzymes, and vesicles are transported from cell body down axon to terminalAt terminal, NTs are synthesized and packaged into vesiclesFilled vesicles dock onto proteins in terminal

ReleaseAction potential opens channels for Ca++ to enter terminal membraneVesicles to undock and move to membraneVesicles fuse with membrane and empty transmitter into synapse (exocytosis)

Receptor ActionIonotropicOpens ion channel in receptor itselfIons produce either excitation or inhibitionFast action

MetabotropicSets off cascade of chemical eventsCan lead to ion channel opening on another proteinCan lead to other, long-term changesSlower action

InactivationDestructionReuptake

More on ReceptorsGatingLigand (activated by NT or drug)Voltage (activated by depolarization)

LocationPostsynapticPresynapticAutoreceptorHeteroreceptor

PresynapticAutoreceptor=

PresynapticHeteroreceptors

Some Receptor and Other ChangesReceptor number (up/down-regulation)Receptor affinity (low/high)Reuptake transporter number/affinityEnzyme levelsTransmitter synthesisAxon growthDendrite growthEtcetera

Hierarchy of NTs of InterestAmino AcidsGlutamate (Glu)GABABiogenic AminesQuaternary AminesAcetylcholine (Ach)MonoaminesCatecholaminesDopamine (DA)Norepinephrine (NE)IndolaminesSerotonin (5-HT)NeuropeptidesOpioid PeptidesEnkephalinsEndorphinsDynorphins(Others: lipids, nucleosides, soluble gases)

Amino Acid NTsHigh concentration in brain (micromolar)Small vesiclesPoint-to-point communicationMostly cortex-to-cortexSensory-motor functionsConsistently excitatory or inhibitoryMainly ionotropic receptorsFast acting, short duration (1-5 ms)Examples: Glutamate, Aspartate, GABA, Glycine

Biogenic AminesMedium concentration in brain (nanomolar)Small vesiclesSingle-source divergent projectionsMainly midbrain to cortexModulatory functionsExcitatory or inhibitory by receptorMore metabotropic receptors than ionotropic, but plenty of bothSlow acting, long duration (10-1000 ms)Examples: Acetylcholine, Epinephrine, Norepinephrine, Dopamine, Serotonin

NeuropeptidesLow concentration in brain (picomolar)Large vesiclesPackaged in vesicles before transport to terminalCo-localized with other transmittersInterneuronalModulatory functionsMostly inhibitoryVirtually all metabotropicSlow acting, long duration (10-1000 ms)Examples: Enkephalins, Endorphins, Oxytocin, Vasopressin

Modulatory FunctionsState-dependent effectsRegulate influence of extrinsic vs. intrinsic activitySynchronization of areas/functionsMotivational/emotional recruitment of mental resources