Announcements • Slides used at tutorial posted to webpage • Last lecture: – Finished Action potentials • Today – Start synaptic transmission Neural Signalling Within neurons electrical Between neurons chemical & electrical Definitions 1. Synapse : the functional contacts between neurons and other cells 2. Synaptic Transmission: the process used by neurons to relay information from one cell to the next Definitions Presynaptic cell Postsynaptic cell Synapse Types of Synapses 1. Electrical Direct flow of electrical current from one cell to the next 2. Chemical Secrete neurotransmitter molecules that activate receptors Electrical synapses • Physical link between two neurons called a gap junction Protein is called connexon Electrical Synapses Action potential in one cell can cause ions to flow through the gap junction into the next cell Inject current Record Reduced depolarization Electrical Synapses Electrical synapses : 1. Can be unidirectional or bidirectional 2. Are very fast 3. Uses A. Electrical synapses first discovered in crayfish neurons involved in escape response B. Synchronizing neural activity, e.g. hormone secreting neurons in the mammalian hypothalamus Chemical synapse Presynaptic nerve terminal Synaptic vesicles Synaptic cleft Neurotransmitter receptors Postsynaptic nerve terminal Chemical Synapses Features: 1. Use chemical neurotransmitters 2. There is a space between the pre- and postsynaptic neuron, called the synaptic cleft 3. Neurotransmitter is stored in synaptic vesicles Chemical Synapses Features: 4. Can be excitatory or inhibitory • Depends on neurotransmitter and receptor 5. Can activate ion-channels or second messenger pathways 6. The amount of transmitter released is variable and can be modulated Real synapse Drosophila neuromuscular junction Synaptic vesicles Synaptic contacts Active Zone Na+ Ca++ Depolarization Sequence of Events at a Chemical Synapse 1. 2. 3. 4. 5. 6. 7. 8. Action potential depolarizes nerve terminal Voltage-gated Ca++ channels open & Ca++ flows into the nerve terminal Ca++ causes synaptic vesicles to fuse with the plasma membrane Neurotransmitters are released into synaptic cleft Neurotransmitter binds to receptors Opens ion channels and positive current flows into postsynaptic cell Current flow gives postsynaptic potential If postsynaptic potential = threshold Action Potential Na+ Ca++ Depolarization Measuring Synaptic Transmission • Frog Neuromuscular Junction Record from muscle Stimulate nerve Postsynaptic potential mV Muscle cell Time (ms) Stimulus Chemical Synaptic Transmission some key questions 1. What is the nature if vesicular release? 2. What is the role of Ca++? 3. What happens to the neurotransmitter after it is secreted? 4. What are the electrical effects on the postsynaptic cell? The Synaptic Vesicle Cycle Endosome Budding Exocytosis Endocytosis Docking Priming Fusion Evidence for Vesicle Cycle Marker found in endosome Marker found in coated vesicles Marker found in vesicles Extracellular Marker (HRP) Evidence for Vesicle Cycle 1. Stimulate synaptic transmission in the presence of extracellular marker (HRP) 2. Wash marker away 3. Examine the intracellular distribution of the marker by electron microscope 4. Marker first seen in coated vesicles 5. After 5-20 minutes, found in endosome 6. After 1 hour found in synaptic vesicles Summary & Concepts 1. Two types of synaptic communication 1. Electrical through gap junctions 2. Chemical neurotransmitters 2. Depolarization, Ca++ influx, and vesicle fusion release neurotransmitter 3. Neurotransmitter opens ion channels changing the electrical potential of the postsynaptic cell 4. Synaptic vesicles go through a cycle of exocytosis and endocytosis