Action Potentials and Synaptic Transmission BIO 219 Napa Valley College Dr. Adam Ross
Review of action potentials
Nodes of Ranvier Nucleus Dendrites Cell body In saltatory conduction, the nerve impulses jump from one node of Ranvier to the next. Node of Ranvier Schwann cell (a) Myelin sheath
Parts of a neuron
Reflex?
Signal transduction between cells Action potentials can carry chemical messages within a single cell, but how do cells talk to one another? The signal must be propagated to another cell Electrical synapse gap junction (uncommon in nervous cells) Chemical synapse neurotransmitter release at synapse
Electrical synapse
Chemical vs Electrical synapses
Chemical Synapse Ionotropic Neurotransmitter binds and opens and ion channel Metabotropic Neurotransmitter binds to receptor causing conformational change and activation of G-protein dependent secondary messengers
Chemical synapse Presynaptic cell: AP travels to axon terminal (synaptic bulb) Depolarization opens voltage gated Ca 2+ channels Ca 2+ promotes neurotransmitter vesicle exocytosis Neurotransmitter is released into synaptic cleft
Chemical synapse Postsynaptic cell: After neurotransmitter is released into synaptic cleft- NT binds to receptor on postsynaptic cell (neuron or muscle fiber) Causes some sort of change in the postsynaptic cell This change is the basis for the propagation of the message or signal Can be excitatory or inhibitory
Excitatory post synaptic potential EPSP Depolarizes post synaptic membrane (V m gets more +) Often the result of the opening of Na + channels Increases the likelihood of an AP firing in postsynaptic cell
Inhibitory post synaptic potential IPSP Hyperpolarizes the postsynaptic membrane (V m gets more -) Can result from the opening of Cl - or K + channels Decreases the likelihood of AP forming in postsynaptic cell
EPSP and IPSP
Ion compositon
Neural integration Synaptic inputs Neurons have multiple inputs from multiple neurons EPSP and IPSP formed at dendrites Integrated to give overall potential to cell Strong EPSP may overcome weak IPSP and vice versa Summation Summation of IPSP and EPSP determines if cell will reach threshold and fire AP Spatial summation- IPSP or EPSP from many synapses add together Temporal summation- EPSP can add together if they occur closely in time
Classes of neurotransmitters Amino Acids GABA (inhibitory) Glutamic Acid (AA precursor) Binds GABA receptor Open Cl- channel Glycine (inhibitory) Binds Glycine receptor Opens Cl- channel Glutamate (excitatory) Binds NMDA, AMPA, and Kainate receptors
GABA recycling
NMDA receptor function
Glutamate: NMDA and AMPA receptors- work together in long term potentiation
Monoaminergic Neurotransmitters Dopamine Serotonin Acetylcholine
Dopamine Functions in the central reward pathway
Methamphetamine Increases cytosolic dopamine at the expense of the vesicular pool
Serotonin Also called 5-HT Binds to 5-HT receptors Involved in depression MDMA (ecstasy) increases 5- HT release from presynaptic cell Binds presynaptic transporter and makes it an exchanger
Antidepressants MDMA Taken a few times to aid with therapy Acts to increase serotonin signaling Helps to treat the underlying cause of PTSD Few or no side effects if only taken in low doses and a few number of time Treatment attempts to cure PTSD by allowing increased effectiveness of counseling and therapy Zoloft/ Paxil Taken daily for long periods Acts to increase serotonin signaling Only treats symptoms Long list of side effects and possibility of permanent changes to brain physio-chemistry Treatment assumes PTSD is a chronic disorder and the best option is to treat symptoms
Cholinergic Signaling Acetylcholine is NT nachr Ionotropic Skeletal muscle machr Metabotropic Cardiac muscle
Catecholamine Neurotransmitters Norepinephrine/ Epi Fight or flight response Several types of receptors Alpha1 (α 1 ): vasoconstriction of GI tract Beta1 (β 1 ): increase of hear rate and force of contraction Beta2 (β 2 ): vasodilation of vasculature associated with skeletal muscle
Epi/ Norepinephrine
Opioid Neurotransmitters Many different endogenous opioid peptides Mu (μ)δ, Kappa (κ), and Delta (δ) receptors Muscle relaxant Analgesic (pain relief) Cardiovascular and respiratory depressant (in brain) Inhibits GI tract function Use of drug causes euphoria and drowsiness Overdose is caused by respiratory and cardiac depression Loss of CO 2 trigger- no desire to breathe even when CO 2 is high
Cannabinoids Endocannabinoids are too numerous to list here CB1 and CB2 receptors Most common G-protein coupled receptors in brain
CB1 Receptor Activated by THC and endocannabinoids THC is what makes you feel stoned Shortens duration of presynaptic AP via camp with K+ current Inhibits Ca 2+ entry (decreased NT exocytosis) via direct G- protein interaction
CB2 Receptor Activated by endocannabinoids and CBD CBD is non-psychoactive Involved in seizures Modulate inflammatory response Decrease perception of pain Medical marijuana that is high in CBD and low in THC is used in children and patients that want to avoid psychoactive effects
What do you think? Cannabinoids Low rates of addiction Mild to zero withdrawal symptoms Anti-nausea No possibility of overdose Can bypass euphoric feeling by activating only CB2 receptors or using THC-A Long term use can impair short term memory formation Low evidence of tolerance Many possible unknown neurodevelopmental effects Potential for patient abuse Lack of standard doses or production methods Opiates Highly addictive Severe withdrawal symptoms Can cause nausea Concerns about overdose Can not bypass euphoric feeling Long term use can cause anxiety, depression, impairment of cognitive function Can become highly tolerant Potential for patient abuse