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Neural transmission Beauty in the nervous system? The Neuron is the Fundamental “working unit” of the nervous system In most respects the neuron is like other cells of our body But is different in that it can produce electrical impulses near its cell body region That move down the axon and lead to the release of specialized neurochemicals (neurotransmitter substances) at the Synapse Synaptic release of Neurotransmitter substances may in turn affect “postsynaptic” neurons; mostly in the dendritic regions Historical perspective:The “Reticular Theory • The nervous system was thought to be a continuous network of fibers…no individual cells The “Golgi stain” helped us to visualize individual neurons And led to: The Neuron Theory There are many types of neurons:Some common types of neurons This is our “Model Neuron” The Neuron is also different in that the axon is typically myelinated by “glial cells” The Shwann cell Oligodendrocytes ( a member of the glia family) There are many types of glial cells: all are thought to primarily provide support functions The Neuronal communication process can be thought of as an “electro-chemical” event • How is the electric signal produced? • How is the Chemical event produced? The Neuron is Like a little battery We use an Oscilloscope to visualize electric charge The resting Membrane potential (RMP) Ions are responsible for the charge of a neuron Cations + Anions- At Rest, ionic substances have different concentrations inside vs. outside the neural membrane Passive vs Dynamic neural responses Comparison Between Passive Potential and Active Potential Description Passive Potential Active Potential Amplitude Graded with stimulus intensity Always the same size Stimulation Requires very little Requires a 15-20 mV change Summation Adds the stimuli strengths Only one potential at a time Spread Decay with distance Actively regenerated Duration As long as the stimulus Constant duration Main channels used Non-gated channels Voltage-gated channels Hyperpolarization and Depolarization • Hyperpolarization- makes the RMP more negative • Depolarization-makes the RMP more positive Comparison Between Passive Potential and Active Potential Description Passive Potential Active Potential Amplitude Graded with stimulus intensity Always the same size Stimulation Requires very little Requires a 15-20 mV change Summation Adds the stimuli strengths Only one potential at a time Spread Decay with distance Actively regenerated Duration As long as the stimulus Constant duration Main channels used Non-gated channels Voltage-gated channels What is special about “threshold?” The forces of Diffusion: Concentration Gradients The forces of Diffusion across a semi-permeable membrane Diffusion also occurs across electrostatic gradients The neural membrane is a semipermeable membrane The Neurons membrane separates the different ions The membrane controls diffusion By opening or closing Ion channels If ion channels are open; diffusion across concentration and electrostatic gradients will occur Triggering the release of RMP energy • How does threshold depolarization trigger a dynamic response? – Changes membrane permeability • Activating/opening ion channels • -”Voltage-gated” Na+ ion channels – Open only when a critical level of depol occurs – Other ion channels then become involved Refractory period Once triggered, the AP is all or none, and “one-way.” Saltatory Propagation Myelenation and size affect speed Multiple sclerosis (MS) is a chronic, potentially debilitating disease that affects the central nervous system, which is made up of the brain and spinal cord. Doctors and researchers think the illness is probably an autoimmune disease, which means that your immune system attacks part of your body as if it's a foreign substance. • • • • • • Multiple Sclerosis is an incurable debilitating disease of the central nervous system. MS affects young to middle aged adults. Approximately 4 million worldwide have this disease. 400,000 of these people live in the United States. It can affect anyone, and can strike at anytime without warning. Once you develop this disease it will be with you for the remainder of your life, as there is no cure or known cause. Multiple Sclerosis is a degeneration of the myelin sheath surrounding nerves in the brain and spinal cord. The part of the body effected by this disease is dependant on the nerves that are damaged. Typical symptoms may include one or more of the following: loss of muscle coordination, unsteadiness, fatigue, speech difficulties, vision degradation, loss of bowel and bladder control and numbness in the extremities. Many people with MS are unable to walk without assistance, requiring wither canes, walkers or wheelchairs. A percentage are bed ridden and unable to care for themselves in any way, required around the clock care. Resetting the RMP Action Potential at the Terminals The Synapse: PRESYNAPTIC and POSTSYNAPTIC processes PRESYNAPTIC Exocytosis Excocytosis involves microtubules Exocytosis • • • • • Voltage-dependent Ca++ channels Ca++ influx Vesicular migration Vesiclular fusion Release of NTs into synapse NTs release into synapse Classical NTs NTs Terminology Acetylcholine/ACH Serotonin/5-HT GABA (gamma-amino-butyric acid) Glutamate/Glu Norpinephrine /NE Dopamine /DA Enkephalin/Endorphin Post synaptic effects Cholinergic serotonergic +/+/- GABA-ergic - Glutamatergic Adrenergic Dopaminergic + +/+/+/- Many other neurotransmitters are derived from precursor proteins, the so-called peptide neurotransmitters. As many as 50 different peptides have been shown to exert their effects on neural cell function. POSTSYNAPTIC PROCESSES: NT receptors EFFECTS OF NTs? Many factors, but all lead to: • IPSPs: inhibiitory post synaptic potentials – Hyperpolarization – Decrease probability of action potential • EPSPs: excitatory post synaptic potentials – Depolarization – Increase probability of action potential Neural Integration Neural Integration occurs mainly at axon hillock and can occur spatially or temporally Axon Hillock EFFECTS OF NTs? • EPSP or IPSP – Depends on receptor subtype Most General division of NT receptors- IONOTROPIC RECEPTORS Metabotropic Receptors Effects depend on receptor subtype And circuits NT-receptor interactions must stop! Enzymatic degradation Eg… Effects of Nerve gas exposure Neuromuscular Effects •Twitching •Weakness •Paralysis •Respiratory failure Autonomic Nervous System Effects •Reduced Vision •Small pupil size •Drooling •Sweating •Diarrhea •Nausea •Abdominal pain •Vomiting Central Nervous System Effects •Headache •Convulsions •Coma •Respiratory arrest •Confusion •Slurred speech •Depression •Respiratory depression Reuptake Here are the SSRIs approved by the Food and Drug Administration (FDA) specifically to treat depression, with their generic, or chemical, names followed by available brand names in parentheses: Citalopram (Celexa) Escitalopram (Lexapro) Fluoxetine (Prozac, Prozac Weekly) Paroxetine (Paxil, Paxil CR, Pexeva) Sertraline (Zoloft) These medications may also be used to treat conditions other than depression. Side effects of SSRIs All SSRIs have the same general mechanism of action and side effects. However, individual SSRIs have some different pharmacological characteristics. That means you may respond differently to certain SSRIs or have different side effects with different SSRIs. SSRI possible side-effects Side effects of SSRIs include: Nausea Sexual dysfunction, including reduced desire or orgasm difficulties Dry mouth Headache Diarrhea Nervousness Rash Agitation Restlessness Increased sweating Weight gain Drowsiness Insomnia Drugs may affect neural transmission in different ways