bjectives Synapses s Temporal & Spatial Summation EPSP & IPSP Coding Memory Synapses a nerve signal AP travels to the end of the axon triggers the release of a neurotransmitter stimulates a new wave of electrical activity in the next cell across the synapse synapse between two s presynaptic postsynaptic can have an enormous number of synapses spinal motor covered by about 10,000 synaptic knobs from other s!!!! 8000 ending on its dendrites 2000 ending on its soma 12-1 in cerebellum of brain, one can have as many as 100,000 synapses 12-2 Synaptic Relationships Between Neurons (a) Soma Axon Presynaptic Synapse Direction of signal transmission Axodendritic synapse Postsynaptic Structure of a Chemical Synapse synaptic knob of presynaptic contains synaptic vesicles containing neurotransmitter many on release plasma membrane waiting to be released others located further away from membrane postsynaptic membrane contains proteins that function as receptors and ligand-regulated ion gates Axosomatic synapse (b) Axoaxonic synapse 12-3 12-4 Structure of a Chemical Synapse Postsynaptic Axon of presynaptic Postsynaptic Microtubules of cytoskeleton Mitochondria Synaptic knob Synaptic cleft synaptic vesicles with neurotransmitter receptors and ligand-regulated ion channels Synaptic vesicles containing neurotransmitter receptor release 12-5 s and Related Messengers more than 100 neurotransmitters!! 4 major categories according to chemical composition 1. acetylcholine in a class by itself 2. amino acid neurotransmitters include glycine, glutamate, aspartate, and -aminobutyric acid (GABA) 3. monoamines synthesized from amino acids after removal of CH group retaining the NH 2 (amino) group major monoamines are: epinephrine, norepinephrine, dopamine (catecholamines) histamine and serotonin 4. Neuropeptides Chains of amino acids 12-6 1
Categories of s s at a Synapse Acetylcholine CH 3 H 3C N + CH 2 CH 2 C CH 3 CH 3 Amino acids H C CH 2 CH 2 CH 2 NH 2 GAB A H C CH 2 NH 2 cine H C CH CH 2 C H NH 2 Aspartic acid H C CH CH 2 CH 2 C H NH 2 tamic acid Monoamines Catecholamines H H CH CH 2 NH CH 2 H Epinephrine H H CH CH 2 NH 2 H Norepinephrine H CH 2 CH 2 NH 2 H Dopamine H CH 2 CH 2 NH 2 N Serotonin N CH 2 CH 2 NH 2 N Histamine Met Tyr Enkephalin Ser Ser Arg ß-endorphin Pro Neuropeptides Thr Met Pro S 4 Leu Met Substance P Asp Tyr Met Trp Met Asp Tyr Thr Ala Pro Asn Leu Val Thr Leu IIe IIe Cholecystokinin Asn Ala Tyr synthesized by the presynaptic released in response to stimulation (An AP!) bind to specific receptors on postsynaptic cell alter the physiology of postsynaptic cell (i.e. cause local ) 12-7 12-8 Effects of s a given neurotransmitter does not have same effect everywhere in the body multiple receptor types exist for a particular neurotransmitter 14 receptor types for serotonin receptor governs the effect the neurotransmitter has on the target cell Synaptic Transmission neurotransmitters are diverse in their action some excitatory (EPSP) some inhibitory (IPSP) effect depends on what kind of receptor the postsynaptic cell has some receptors are ligand-regulated ion gates some receptors act through second-messenger systems three kinds of synapses with different modes of action excitatory cholinergic synapse inhibitory GABA-ergic synapse excitatory adrenergic synapse synaptic delay arrival of signal at axon terminal to AP 12-9 12-10 Involve Acetylcholine Excitatory Cholinergic Synapse ACh excites some postsynaptic cells (skeletal muscle) Na + enters the cell it spreads out along the inside of the plasma membrane and depolarizes it producing a local if it is strong enough and persistent enough it opens voltageregulated ion gates in the trigger zone AP!!! Presynaptic 3 Ca 2+ 1 2 Na + 4 5 K + ACh Presynaptic Please note that due to differing operating systems, some animations will not appear until the presentation is viewed in Presentation Mode (Slide Show view). You may see blank slides in the Normal or Slide Sorter views. All animations will appear after viewing in Presentation Mode and playing each animation. Most animations will require the latest version of the Flash Player, which is available at http://get.adobe.com/flashplayer. Postsynaptic 12-11 2
Excitatory Adrenergic Synapse Adrenergic synapse employs the neurotransmitter norepinephrine (NE) (aka noradrenaline) ( NE and other monoamines, and neuropeptides act through second messenger systems such as cyclic AMP (camp) The receptor is not an ion gate, but a transmembrane protein associated with a G protein Excitatory Adrenergic Synapse Secondary Messenger System has advantage of enzyme amplification single molecule of NE can produce vast numbers of product molecules in the cell receptor 1 Norepinephrine G protein 2 3 Presynaptic Postsynaptic Adenylate cyclase ATP camp Ligandregulated gates opened 5 Na + + + + 12-13 4 Multiple Enzyme activation possible 6 effects 7 Metabolic changes Genetic transcription Enzyme synthesis Postsynaptic Inhibitory GABA-ergic Synapse GABA-ergic synapse employs -aminobutyric acid as its neurotransmitter nerve signal triggers release of GABA into synaptic cleft GABA receptors are chloride channels (Cl- anions) Cl - enters cell and makes the inside more negative than the resting membrane Membrane becomes Hyperpolarized Postsynaptic is inhibited - less likely to fire 12-15 Cessation of Synapse Usually is its receptor for brief time replaced by another 1. stop adding neurotransmitter get rid of that which is already there stop signals in the presynaptic nerve fiber 2. Getting rid of neurotransmitter diffusion into nearby ECF astrocytes in CNS absorb it and return it to s Reuptake and breakdown synaptic knob reabsorbs amino acids and monoamines by endocytosis break neurotransmitters down with enzymes Degradation in the synaptic cleft Enzymes e.g., acetylcholinesterase in synaptic cleft degrades into acetate and cholin 12-16 Neuromodulators hormones, neuropeptides, and other messengers that modify synaptic transmission may stimulate installation of more receptors in postsynaptic membrane may alter rate of neurotransmitter synthesis, release, reuptake, or breakdown enkephalins a neuromodulator family small peptides that inhibit spinal inters from transmitting pain signals to the brain nitric oxide (N) simpler neuromodulator a lightweight gas release by the postsynaptic s in some areas of brain concerned with learning and memory diffuses into presynaptic stimulates release of more neurotransmitter s way of telling the another to give me more Neural Integration synaptic delay slows transmission of nerve signals more synapses in pathway, longer it takes information to get from its origin to its destination synapses are not due to some limitation resulting from nerve fiber length gap junctions allow some cells to communicate more rapidly than chemical synapses then why do we have synapses? the more synapses a has, the greater its informationprocessing capabilities. neural integration = ability of s to process information, store and recall it, and make decisions 12-17 12-18 3
mv Postsynaptic Potentials - EPSP Excitatory postsynaptic s (EPSP) any voltage change increasing the chance of a firing. usually results from Na + flowing into the cell typical has a resting membrane of - ~70 mv and threshold of about -55 mv Any change getting membrane closer to -55 is EPSP Postsynaptic Potentials - IPSP inhibitory postsynaptic s (IPSP) any voltage change away from threshold that makes a less likely to fire neurotransmitter hyperpolarizes postsynaptic cell making it more negative than the RMP - less likely to fire produced by neurotransmitters that open ligand-regulated chloride gates glycine and GABA produce IPSPs and are inhibitory acetylcholine (ACh) and norepinephrine are excitatory to some cells and inhibitory to others depends on the type of receptors on the target cell ACh excites skeletal muscle, but inhibits cardiac muscle due to the different type of receptors 12-19 12-20 Postsynaptic Potentials 0 Summation A can receive input from thousands of other s 20 40 60 80 (a) 0 20 40 mv mv Threshold EPSP Resting membrane Repolarization Depolarization Stimulus Time Threshold Some synapses produce EPSPs while others produce IPSPs Post-synaptic s response depends on whether net input is excitatory or inhibitory Summation process of adding up postsynaptic s and responding to their net effect occurs in the trigger zone The balance between EPSPs and IPSPs enables the nervous system to make decisions 60 80 IPSP Resting membrane (b) Stimulus Hyperpolarization Time 12-21 12-22 Summation of EPSPs Temporal and Spatial Summation +40 +20 0 20 Action 1 Intense stimulation by one presynaptic (a) Temporal summation 3 Postsynaptic fires 2 EPSPs spread from one synapse to trigger zone 40 Threshold 60 EPSPs 80 Stimuli Time Resting membrane 12-23 3 Postsynaptic fires 2 EPSPs spread from several synapses 1 Simultaneous stimulation to trigger zone by several presynaptic s (b) Spatial summation 12-24 4
Facilitation, and Inhibition Neurons often work in groups to modify each other s action facilitation one enhances the effect of another one combined effort of several s - summation of EPSP!!!!!! presynaptic inhibition process in which one presynaptic suppresses another one reduces or halts unwanted synaptic transmission I releases inhibitory GABA Neural Coding CNS recieves a coded message 1. Where is the message coming from? labeled line code each nerve fiber to brain leads from a specific fiber Brain recognizes where its from and what stimulus type Signal in presynaptic Signal in inhibitory Signal in presynaptic 2. What type of stimulus is it? (What type sent info) No activity in inhibitory I I 3. How strong is the message? (intensity) - Frequency of APs CNS can judge stimulus strength from the firing frequency of afferent s No neurotransmitter release here Inhibition of presynaptic IPSP S No neurotransmitter S release here Excitation of postsynaptic (a) EPSP R No response in postsynaptic (b) R 12-25 12-26 Neural Coding Action s Neural Pools and Circuits s functioning in large groups, each of which consists of millions of inters concerned with a particular body function control rhythm of breathing moving limbs rhythmically when walking 2 g 5 g information arrives at a neural pool through one or more input s branch repeatedly and synapse with numerous inters in the pool Discharge zone input synapses many times w postsyn. (temporal summation) Facilitated zone require facilitation more pre- s required to fire ne or more s 10 g 20 g Time Figure 12.28 12-27 Facilitated zone Discharge zone Facilitated zone 12-28 Types of Neural Circuits Memory and Synaptic Plasticity Diverging Converging utput Physical basis of memory is a pathway through the brain called a memory trace or engram along this pathway, new synapses were created or existing synapses modified to make transmission easier synaptic plasticity ability of synapses to change synaptic potentiation - process of making transmission easier Reverberating utput Parallel after-discharge Figure 12.30 kinds of memory immediate, short- and long-term memory correlate with different modes of synaptic potentiation utput utput 12-29 12-30 5
Immediate Memory immediate memory ability to hold something in your thoughts for just a few seconds essential for reading ability feel for the flow of events (sense of the present) our memory of what just happened echoes in our minds for a few seconds Short-Term or Working Memory short-term memory - lasts from a few seconds to several hours quickly forgotten if distracted calling a phone number we just looked up reverberating circuits Synaptic facilitation causes memory to last longer tetanic stimulation rapid arrival of repetitive signals at knob causes Ca 2+ accumulation in knob Release of more and more neurotransmitter postsynaptic cell more likely to fire 12-31 post-tetanic potentiation - to jog a memory Ca 2+ level in synaptic knob stays highly elevated AP causes massive amount of neurotransmitter release 12-32 Long-Term Memory types of long-term memory declarative - retention of events that you can put into words procedural - retention of motor skills We think some LTM involves physical remodeling of synapses new branching of axons or dendrites long-term potentiation changes in receptors and other features increases transmission across experienced synapses effect is longer-lasting Molecular Changes & Long-Term Memory long-term potentiation Involves NMDA receptors and Mg +2 NMDA receptors on dendrites usually blocked by Mg +2 ions when bind glutamate and receive stimuli, they repel Mg +2 channel opens Ca +2 enters dendrite Ca +2 acts as second messenger more synaptic knob receptors are produced synthesizes proteins involved in synapse remodeling releases nitric oxide that triggers more neurotransmitter release at presynaptic 12-33 12-34 Long-Term Potentiation (LTP) Alzheimer Disease 100,000 deaths/year 11% of population over 65; 47% by age 85 memory loss for recent events, moody, combative, lose ability to talk, walk, and eat Increased Ca+ ion channel openings i.e., neurotransmitter released (tamate receptor) deficiencies of acetylcholine (ACh) and nerve growth factor (NGF) diagnosis confirmed at autopsy atrophy of gyri (folds) in cerebral cortex neurofibrillary tangles and senile plaques formation of beta-amyloid protein from breakdown product of plasma membranes genetics implicated Increases EPSP Increased Ca+ causes Protein synthesis for Pre-synaptic proteins (dendritic spines) (calmodulin-dependent Protein kinase II) 8-38 treatment - halt beta-amyloid production Give NGF or cholinesterase inhibitors! 12-36 6