Neurophysiology Part 3 - Synaptic Transmission and Action Potentials PDF

Andre Azevedo, DVM, MSc Locum Professor of Veterinary Physiology [email protected]  At the end of the lecture, students should be able to: Differentiate types of synapses (chemical x electrical) Differentiate ionotropic and metabotropic receptors Describe conventional...

Andre Azevedo, DVM, MSc Locum Professor of Veterinary Physiology [email protected]  At the end of the lecture, students should be able to: Differentiate types of synapses (chemical x electrical) Differentiate ionotropic and metabotropic receptors Describe conventional and unconventional neurotransmitters Describe graded potentials and how they contribute to the formation of action potentials Differentiate spatial and temporal summation of graded potentials Describe the saltatory conduction FYI  https://www.youtube.com/watch?v=LT3VKAr4roo https://www.youtube.com/watch?v=iBDXOt_uHTQ  Neurons are the core components of the brain, spinal cord, and nerves  The dendrites integrate the incoming information and determine whether action potentials will be produced by the neuron In some neurons, the dendrites are covered with small membranous protrusion called DENDRITIC SPINES Each spine can synapse with different axons One dendrite can communicate with hundred axons Dendritic branching pattern of a neuron can change and may increase or decrease Enriched or stimulatory environment is associated with the growth of dendrites  Axons may be only a few micrometers or may be over 10 meters long, depending on the species and location Owing to their length, axons usually contain the majority of the cell cytoplasm and also several organelles Neurofibrils, neurotubules, small vesicles, lysosomes, mitochondria, and enzymes Axonal proteins are synthesized in the soma and transported to the axon Cytoskeleton and different proteins work to transport several different cargoes in both directions Ex: Organelles such as mitochondria; vesicles containing neurotransmitters ANTEROGRADE TRANSPORT IS RELATED TO SYNAPTIC COMPONENTS Ex: Flow of synaptic vesicles and mitochondria RETROGRADE TRANSPORT IS RELATED TO CARGO FOR DEGRADATION Ex: recycled membrane vesicles 1. CHEMICAL SYNAPSES Most common forms of synapses – usually unidirectional transmission The presynaptic neuron secretes a NEUROTRANSMITTER that will act on receptor proteins in the postsynaptic neuron Can be EXCITATORY or INHIBITORY NEUROTRANSMITTERS There are many different kinds, and new ones are still being discovered! CONVENTIONAL Share some basic features relative to older definitions Stored in vesicles, released when Ca enters the axon terminal in response to APs Act by binding to receptors on the membrane of the postsynaptic cell UNCONVENTIONAL Several classes that do not follow all of the usual rules Not stored in vesicles Can carry signals backward (from postsynaptic to presynaptic) Do not depend on receptors – can cross the membrane and act directly on molecules inside the cell NEUROTRANSMITTERS CONVENTIONAL 1. SMALL MOLECULE NEUROTRANSMITTERS (small organic molecules) Aminoacids - Glutamate; inhibitory GABA – Gamma-aminobutyric acid, glycine Amines – Acetylcholine, Dopamine, norepinephrine, epinephrine, serotonin, histamine Purines – ATP and adenosine 2. LARGE MOLECULE NEUROTRANSMITTERS (made up of 3 or more amino acids) Endorphines and Encephalins – inhibit pain Substance P – carries pain signals Neuropeptide Y – several actions including, increasing food intake and storage of energy as fat NEUROTRANSMITTERS UNCONVENTIONAL 1. ENDOCANNABINOIDS Lipid-based neurotransmitters that bind to cannabinoid receptors (CB1 and CB2) Synthetized by the body – Anandamide (AEA) and 2-arachinonyl-glycerol (2-AG) Found in plants like hemp (Cannabis sativa) - THC and CBD Endocannabinoid system is involved in a lot of physiological processes, including appetite, pain sensation, mood, memory, and pharmacological effects of Cannabis sativa 2. GASOTRANSMITTERS Small molecule of gas; freely permeable to membranes Nitric Oxide (NO), Carbon Monoxide (CO), Hydrogen Sulfide Ex: Blood vessels signaling to smooth muscle; NO is produced by some neurons and is required for the normal performance of eye movement  NICOTINIC ACETYLCHOLINE RECEPTOR The action of the neurotransmitter in the postsynaptic membrane depends on receptor proteins A. IONOTROPIC RECEPTORS Neurotransmitter receptor that directly gate ion channels CATION CHANNELS – opened by excitatory neurotransmitters Induce depolarization – Ex: Na+ Channel ANION CHANNELS – opened by inhibitory neurotransmitters Induce hyperpolarization – Ex: Cl- Channel  The action of the neurotransmitter in the postsynaptic membrane depends on receptor proteins B. METABOTROPIC RECEPTORS Neurotransmitter receptors that act through second messenger systems G PROTEIN-COUPLED RECEPTORS Open specific ion channels through the postsynaptic membrane Activate the cAMP pathway Activate one or more intracellular enzymes Activate gene transcription 2. ELECTRICAL SYNAPSES The cytoplasm of adjacent cells is directly connected by clusters of ion channels called GAP JUNCTIONS Allow free movement of ions from the interior of one cell to the interior of the next cell Bidirectional transmission Coexist and interact with chemical synapses Promotes synchronous firing of a group of interconnected neurons  workasahormone would EN PASSANT SYNAPSES AXOSECRETORY EN PASSANT IS FRENCH FOR SYNAPSES “IN PASSING”,BECAUSE THE SYNAPSES ARE USED AS THE ELECTRICAL SIGNAL PASSES BY TO THE AXON TERMINAL  noglandulartissue A typical neuron has a resting potential (potential across the membrane) of −60 to −70 millivolts The interior of the cell is negatively charged relative to the outside Na-K-ATPase  A neuron receives hundreds of inputs from other neurons In response to neurotransmitters from presynaptic neurons Brief local changes in postsynaptic membranes are generated These local membrane potentials are called GRADED POTENTIALS Their amplitude is directly proportional to the intensity of the stimulus applied at synaptic sites Each synaptic site generates graded potentials Thousands of graded potentials occur at cell bodies and dendrites They travel to reach the axon hillock or trigger zone  The trigger zone is where graded potentials are integrated to generate action potentials This zone is more sensitive to the depolarizing action of the local currents In order to initiate an action potential, graded potentials must reach a level THRESHOLD POTENTIAL or THRESHOLD VOLTAGE the minimal voltage change to trigger an action potential -55mV  Once the sum of graded potentials exceeds the threshold, an action potential will be triggered The AP propagates along the axon basically ifit'snotstrongenough noAP If the depolarization does not reach the threshold, no action potential will occur The graded potentials decay  depends thisarrangement Graded potentials modulate the postsynaptic neuron by shifting the resting membrane potential They can shift toward the threshold potential potential membrane DEPOLARIZATION = shift MP toward more positive Excitatory neurotransmitters – open cation channels Ex: Glutamate – binds to specialized receptors that allow the transport of Ca, K, and Na EXCITATORY POSTSYNAPTIC POTENTIALS (EPSP) – depolarizing graded potentials Drives the MP toward the threshold These synapses are called EXCITATORY SYNAPSES  Graded potentials modulate the postsynaptic neuron by shifting the resting membrane potential They can shift away from the threshold potential HYPERPOLARIZATION = shift MP toward more negative Inhibitory neurotransmitters – opens anion channels Ex: GABA - binds to ligand-gated chloride channels INHIBITORY POSTSYNAPTIC POTENTIALS (IPSP) hyperpolarizing graded potentials These synapses are called INHIBITORY SYNAPSES  more causeshyperpolarization  Numerous presynaptic axons converge on a postsynaptic neuron generating thousands of EPSPs and IPSPs The axon hillock is able to process all graded potentials by algebraic processing Adding or subtracting potential changes The axon hillock continues to process graded potentials as long as: The sum of all graded potentials stays under the threshold The presynaptic changes occur faster than the decay rate of the graded potential in the post- synaptic neuron  There are 2 modes of summation: SPATIAL SUMMATION Graded potentials induced by different synapses summate in the postsynaptic neuron Simultaneous summation of inhibitory (IPSP) and excitatory (EPSP) graded potentials also occur TEMPORAL SUMMATION Successive discharges from a single presynaptic terminal summate in the post- synaptic neuron If they are rapid enough  bothfire sametim oneespsslightlydepolarite tnenanother afterwards occurs Esps shortly É Atta's nY'd's'athtite ex nfyronmudf.tntjf9fthfaKesneaYYohisfiring  time twoneuronsfiringsame  All action potentials generated at the trigger zone are identical and propagate without losing strength Dominos effect Enables it to travel long distances The speed of conduction depends on the following: Bohdan Axon diameter The degree of myelinization Small Unmyelinated Large Myelinated as low as 0.25 m/sec as fast as 10 m/sec  Action potential occurs only at the Nodes of Ranvier in myelinated fibers The Nodes of Ranvier are rich in ion channels Action potentials “jump” from node to node Na influx depolarizes the membrane The electrical current flows through the axoplasm inside the axon Passive and decremental Na current The impulse is transmitted from node to node AP is regenerated at nodes of Ranvier  FYI More info on hypomyelination (Shaking Puppy Syndrome): https://vetmed.umn.edu/research/research-labs/canine-genetics-lab/canine-genetics- testing/siberian-husky-health-panel https://www.merckvetmanual.com/nervous-system/myelin-disorders/myelin-disorders-in- animals https://vgl.ucdavis.edu/test/hypomyelination-weimaraner https://bvajournals.onlinelibrary.wiley.com/doi/full/10.1002/inpr.3