Presentation on theme: "Neuronal Transmission BN Fall 2011 Julia Sobesky."— Presentation transcript:
Neuronal Transmission BN Fall 2011 Julia Sobesky
Outline Types of synapses Electrical Chemical Neurotransmitters Criteria Types Release Inactivation Receptor types Ionotropic Metabotropic Ligand binding Plasticity
Electrical synapse: gap junctions ~3nm apart Very fast communication Direct pore between cells, allows bidirectional flow of ions 6 connexins= 1 connexon Allows rapid and synchronous firing of interconnected cells
Why would we need anything more? Why don’t our brains just use electrical transmission?
Benefits of Chemical signaling 60+ different NTs and neuromodulators Each NT can have up to 15 different receptors Co-localization of several NTs in one synapse One neuron can have TONS of different synapses Simple or complex post-synaptic responses
The chemical synapse ~20-50 nm apart NTs released by pre- synaptic cell bind receptors on post-synaptic membrane EPSP, IPSP or complex responses *** The RECEPTOR determines the response, not the NT ***
Criteria for NTs Synthesized in pre- synaptic cell Activity dependent release Mechanism for deactivation Predictable pharmacological activity
Major classes of neurotransmitters Small neurotransmitter molecules Synthesized near axon terminals Acetylcholine, monoamines, indolamines, amino acids Large neurotransmitter molecules- Neuropeptides Synthesized in soma hormones enkephalin/ endorphin Soluble gasses nitric oxide carbon monoxide
Small Neurotransmitters 1. Amino Acids Glutamate/ Gamma-aminobutyric acid (GABA) MAJOR NTs in the CNS/ All over 2. The Monoamines Catecholamines Dopamine- DA- reward/movement Norepinephrine- NE –sympathetic Epinephrine-released from adrenals Indolamines Serotonin -5-HT 3. Acetylcholine (ACh)
Then what? NTs are synthesized at terminal and packaged Or Neuropeptides are transcribed, translated, packaged and trafficked down to the terminal How does an Action Potential initiate their release?
Exocytosis SNARE Proteins Ca++ facilitated
What happens to NTs after release? Diffusion through synapse to post-synaptic cell NT binding to receptors is TRANSITORY, more NT around to bind, the greater the receptor effects …….
2 Main Types of Receptors Ionotropic Ligand-gated ion channels Directly alters the membrane potential Metabotropic Slower, but can have greater effects 2 types: G-protein coupled Tyrosine Kinase receptors
Ionotropic Receptors Excitatory (EPSP) or Inhibitory (IPSP) responses K+, Na+, Ca++ CL- Some can be ligand and voltage-gated (NMDA)
Complex effects of metabotropic receptors NO PORE, but binding can initiate: 2 nd messenger system Other products could open ion channels Modulate enzyme activity Regulate ion channels in membrane Initiate gene transcription/translation
What happens to NTs after release? Diffusion through synapse to post-synaptic cell NT binding to receptors is TRANSITORY, more NT around to bind, the greater the receptor effects NT must be cleared removal just as important as release Multiple things can happen….
Uptake and degradation
Glial Sponge Glial cells can act as buffers for excess NTs Can process and release NTs Passive diffusion away from the synapse Why?
NT binding to receptor shape-specific Lock and key arrangement Endogenous vs. exogenous Drugs work because we already have the receptors in place to receive them Drug actions are so intense because they cause actions so far above and beyond what endogenous compounds do Agonists Antagonists Full vs. partial Competitive vs. non- competitive Allosteric
Receptor agonists and antagonists
Organization dictated by experience Synapses can grow and retract, continually being altered by use Plasticity can occur in a variety of ways: Create new synapses Strengthen or weaken existing synapses Break old connections
Synaptic connections change over time
Putting it all together: Neuropharmacology Tolerance develops due to cellular and receptor alterations in response to chronic drug use The changes also mediate withdrawal symptoms Withdrawal= opposite of drug effects Depression is most likely not due to a lack of serotonin (i.e. SSRIs) …Serotonin receptor is metabotropic Severe alcohol withdrawal can kill you: Seizures Glutamate excitotoxicity