Ch 13 neurons - Animal Physiology.txt

• Role: Mediates Fast, synchronous action
• Advantages
• 1: current flow is INSTANTANEOUS
• 2: current flows EITHER DIRECTION (not polarized)…could be DISadvantage
• 3: Continuity between cells via GAP JXNS bridged by CONNEXON protein CHANNELS
• Disadvantage
• 1: Electrical synapses ALWAY Excitatory (not inhibitory)

• 1: 20-30nm synaptic cleft connecting (barrier to DIRECT communication)
• 2: Pre-synaptic bouton contains Neurotransmitter molecules stored in SYNAPTIC VESICLES
• 3: Post-synaptic neuron holds RECEPTOR MOLECULES to bind to neurotransmitters

• Active zone: site of vesicle release
• Post-synaptic densities: sites of high neurotransmitter RECEPTORs
• Scaffold proteins: aid in organizing proteins and receptors at synapse
• Dendritic spines: Site of Excitatory Synapses-Allow for INCREASED Surface Area for signals

• 1. Ca enters: Action potential Depolarizes axon terminal OPENING Ca Channels for Ca Entry to cell
• 2. Vesicle fusion: Ca ions trigger vesicles to fuse to active zones on bouton
• 3. Ionotropic: Ion neurotransmitter receptors OPEN allowing IONS into post-synaptic cells (ie Na entry causes DEpolarization of post-syn)
• 4. Metabotropic: Metabotropic receptors (GPCRs) are activated by neurotransmitters to initiate cascade of eents to produce 2nd messengers (cAMP)

• 1: Can be excitatory OR inhibitory
• 2: Can only interact ONE WAY
• 3: AMPLIFICATION Of POST-Synaptic CURRENT Flow: release of vesicles and transmitters can open MANY channels to amplify
• 4: MODIFIABLE in their properties (vs electrical syn)

• EPSP: Excitatory post-syn potential allows for Depolarization (ie: Glutamate - opens channels to allow for Na and K to go INTO post-syn cell)
• IPSP: Inhibitory post-syn potential cause HYPERpolarization (ie: GABA diffuses to Post-syn membrane and allows for CHLORIDE ENTRY into Post-syn cell)

• Can combine both IPSP and EPSPs generated
• temporal: combination of SAME nerve repeatedly stimulating rapidly
• spatial: combination of simultaneous EPSPs occurring at DIFFERENT nerves

• Neurotransmitter is Acetylcholine (located in vesicles)
• Diffuses into post-syn receptors where it BINDS
• Allowing for Na entry into post-syn cell and K moves out (DEPOLARIZATION)
• Action potential is Triggered!
• REUPTAKE of ACh by Acetylcholinesterase breakdown into choline
• Choline moves through choline transporter on pre-syn membrane

• 1. Tethering: Quanta packets move towards Active Zone, attaching REVERSIBLY to SNARE proteins on membrane
• 2. Docking: Quanta vesicles bind to t- and v-SNARE IRREVERSIBLY
• 3. Priming: Ca enters via channels (Depolarization causes this) and binds to Synaptotagmin..triggering
• 4. Fusion: Ca-synaptotagmin causes CONFORMATIONAL change leading to fusion with the membrane and exocytosis of neurots
• 5. Endocytosis of vesicle: ATP dependent with association of protein Clathrin

Vesicles releasing neurotransmitters, each contain several 1000 neurotransmitters

• Small molecule neuotransmitters:
• Acetylcholine and Glutamate (most fast EPSPs): ionotropic (causes EPSPs)
• Dopamine: metabotropic (G protein - causes IPSPs)
• GABA (most fast IPSPs): Ionotropic (causes IPSPs)
• Also peptide neurotransmitters: multiple known

Neurons can release multiple neurotransmitters, usually 1 small molecule and multiple peptide transmitters

• Peptide are produced in Neuronal cell body vs at axon terminal w others
• Peptide inactivated by peptidases vs reuptake or enzymes w other
• Peptide has HIGH freq stim vs slow w other

• 1. NT must be be PRESENT at pre-syn terminal and
• 2. RELEASED upon pre-syn stimulation
• 3. NT when added to extracell space must mimic effects of pre-syn stimulation
• 4. MECHANISM for REMOVAL of NT should exist
• 5. DRUG EFFECTS on NT may aid in determinig

• Receptors are used to mediate MULTIPLE Effects, in some cases by the same receptors (ie; ACh receptors - example below)
• ie: In Skeletal muscle, ACh receptor stimulated by nicotine (nicotinic receptor) works to aid in excitation via EPSPs
• In heart muscle, ACh receptor stimulated by Muscarine (muscarinic receptor) aids in IPSPs

• There are evolutionary similarities among vertebrate also found in Nervous system of invertebrates (ie GABA, dopamine, seratonine)
• These neurotransmitters have been evolutionarily conserved, but their ROLE may be different depending on the organism
• Even peptide neutrotransmitters have been shown to have similar protein families showing their importance evolutionarily

• RECEPTOR is the CHANNEL
• 1. Opening is ALL or NOTHING
• 2. Probability of opening is DEPENDENT on NT
• 3. Ionic current thru channel provides Synaptic POTENTIAL
• 4. Currents can be SUMMATED to equal synaptic current

• Nicotinic ACh receptor
• Contains five alpha subunits surrounding ion channel
• Requires binding of 2 NTs allowing opening to contribute to PSP

• METABO: Indirect mode of action (GPCR). Produces Slow, but LONG Lasting effect
• IONO: DIRECT mode of action (ion channels). Produces Fast, Short effects

• Norepinephrine acts on GPCR
• GPCR activates G-protein

• has alpha, beta and gamma units
• a-subunit releases GDP when activated, in exchange for GTP
• a-subunit dissociates from rest and binds to adenlyl cyclase
• cyclase converts ATP to cAMP
• cAMP ACTIVATES cAMP protein kinases
• These kinases PHOSPHORYLATE proteins, such as MEMBRANE, CYTO or NUCLEAR proteins
• ION Channels: G-proteins can activate them DIRECTLY

Muscarinic ACh receptors act as GPCRs to act with INHIBITORY action

• Habit: DECREASE in reflex response when stimulus is repeated
• Senz: ENHANCEMENT of reflex response to stimulus, when 2ND novel stimulus presented
• ie Aplysia fish, gills amplitude of withdrawl diminishes with repeated repeated low freq stim but when hit on the head the response to stim of gills is large again

• Habit: DECREASE in QUANTA number (so less neurotransmitters released) due to Inactivation of Ca Channels
• Senz: the sensitizing stimulus INCREASES Amount of NT released Per Impulse, due to INCREASED Ca Influx

• BOTH
• First, Ionotropic: Produces EPSPs, but ONLY work when post-syn is DEPOLARIZED (AMPA receptors aid in depolarization allowing Na entry)
• ActioN: Glutamate activates NMDA receptor, but Mg blocks the ion channel. DEPOLarization causes release of Mg into synapse, and then Ca and Na can flow in (and K out)
• Then, METABOTROPIC: The Ca that it allow into the post-syn cell acts as 2nd Messengers to activate Ca dependent protein kinases and allow more AMPA vesicles (containing AMPA glutamate receptors) to fuse to membrane to generate ENHANCED POST-SYN response

Long-lasting ENHANCEMENT of Synaptic transmission following INTENSE long-lasting stimulation