Ch. 4 - neural conduction and synaptic transmission PDF

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Chapter 4 – Neural Conduction and Synaptic Transmission LO 4.1 Recording the Membrane Potential   

Membrane potential – the difference in electrical charge between the inside and outside of the cell. Microelectrodes – extremely fine recoding electrodes, which are used for intracellular recording. Resting potential – the steady membrane potential of a neuron at rest, usually about -70 mV o More negative inside and positive outside

LO 4.2 Ionic Basis of the Resting Potential    

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Ions – positively and negatively charged particles. Ion channels – pores in neural membranes through which specific ions pass. In Resting Potential: more Na+ ions OUTSIDE the cell, and more K+ ions INSIDE the cell. 2 Types of Pressure for Na+ ions to enter resting neurons 1. Electrostatic pressure: the -70 mV charge attracts the positively charged Na+ ions into resting neurons. 2. Pressure from random motion for Na+ ions to move down their concentration gradients (From HIGH concentration  LOW concentration). In Resting Neurons – Sodium ion channels are CLOSED and Potassium channels are OPENED; thereby preventing sodium ions rushing into neurons. Sodium-Potassium pumps – an ion transporter that actively exchanges 3 Na+ ions inside the neuron for 2 K+ ions outside.

LO 4.3 Generation, Conduction, and Integration of Postsynaptic Potentials 

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When a neurotransmitter molecule bind to postsynaptic receptors, there are 2 effects: o Depolarize – decrease the resting membrane potential o Hyperpolarize – increase the resting membrane potential Excitatory postsynaptic potentials (EPSPs) – postsynaptic depolarizations; increase the likelihood that the neuron will fire. Inhibitory postsynaptic potentials (IPSPs) – postsynaptic hyperpolarizations; decrease the likelihood that the neuron will fire. Both EPSPs and IPSPs are graded responses – amplitudes are proportional to the intensity of the signals that elicit them; weak signals  small postsynaptic potentials (vice versa).

2 Characteristics of Postsynaptic Potentials 1. RAPID and instantaneous = duration of EPSPs and IPSPs varies, but are transmitted at great speeds. 2. DECREMENTAL = EPSPs and IPSPs decrease in amplitude as they travel through the neuron LO 4.4 Integration of Postsynaptic Potentials and Generation of Action Potentials  Previously believed that action potentials were generated at the axon hillock, but are actually generated in the adjacent section of the axon, called the axon initial segment.

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Chapter 4 – Neural Conduction and Synaptic Transmission  

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Threshold of Excitation – The level of depolarization necessary to generate an action potential; usually about -65 mV. Action Potential (AP) – A massive momentary reversal of a neuron’s membrane potential from about -70 mV to about +50 mV. o NOT graded responses, but are ALL-OR-NOTHING responses. Integration – adding or combining a number of individual signals into one overall signal. o Spatial summation – The integration of signals that originate at different sites on the neuron’s membrane. 3 Kinds >>  2 simultaneous EPSPs sum to produce a greater EPSP  2 simultaneous IPSPs sum to produce a greater IPSP  Simultaneous IPSP and EPSP cancel each other out o Temporal summation – the integration of neural signals that occur at different times at the same synapse. 2 Kinds >>  2 EPSPs elicited in rapid successive sum to produce a larger EPSP  2 IPSPs elicited in rapid succession sum to produce a larger IPSP

LO 4.5 Conduction of Action Potentials  Voltage-activated ion channels – ion channels that open or close in response to changes in the level of the membrane potential. 3 Phases of the Action Potential 1. Depolarization (Rising Phase) = Na+ channels open and K+ channels close a. Na+ ions rush in through the voltage-activated sodium channels b. The membrane potential changes from -70 to +50 mV c. Influx of Na+ ions triggers the opening of K+ channels d. K+ ions are driven out of the cell 2. Repolarization = Na+ channels close; K+ continues to leave until resting potential is achieved again. 3. Hyperpolarization = K+ channels start to close a. A state created when too many K+ ions flow out of the neuron because the potassium ion channel closes slowly

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Chapter 4 – Neural Conduction and Synaptic Transmission

LO 4.6 Refractory Periods  Absolute refractory period – a brief period (typicall 1-2 millisecons) after the initiaton of an action potential during which it is impossible to eleict another action potential in the same neuron.  Relative refractory period – a period after the aboslute refractoroy period uring which a higer-thannormal amount of stimulation is necessary to make a neuron fire. Refractory Period Important for 2 Characteristics 1. AP travel in only ONE DIRECTION – action potential cannot reverse direction 2. The rate of neural firing is related to the intensity of the stimulation, it fires and then fires again as soon as its absolute refractory period is over. The neuron does not fire again until both the absolute and relative refractory periods have run their course. LO 4.7 Axonal Conduction of Action Potentials  Conduction of action potentials along an axon differs from conduction of EPSPs and IPSPs o Conduction of APs is nondecremental  APs DO NOT grow weaker as they travel along the axonal membrane. o Aps are conducted more slowly than postsynaptic potentials (EPSPs and IPSPs)  Why are they different? B/c the conduction of EPSPs is PASSIVE, whereas the axonal conduction of action potentials is largely ACTIVE.  Axonal conduction is thought of as a… single wave of excitation spreading actively at a constant speed along the axon, rather than as a series of discrete events.  The wave of excitation triggered by the generation of action potential near the axon hillock always spread passively back through the cell body and dendrites of the neuron.  Antidromic conduction = axonal conduction opposite to the normal direction; conduction form axon terminals back toward the cell body.  Orthodromic conduction = axonal conduction in the normal direction – from the cell body toward the terminal buttons. 1) Postsynaptic potentials (PSPs) are elicited on the cell body and dendrites 2) PSPs are conducted decrementally to the axon. 3) When the summated PSPs exceed the threshold of excitation at the axon initial segment, an action potential (AP) is triggered. 4) The AP is conducted nondecrementally down the axon to the terminal buttons. 5) Arrival of the AP at the terminal button triggers exocytosis.

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Chapter 4 – Neural Conduction and Synaptic Transmission Conduction in Myelinated Axons  Conduction in myelinated axons are FASTER than in unmyelinated axons o Myelination increases the speed of axonal conduction.  Salutatory conduction – transmission of APs in myelinated axons.  Nodes of Ranvier – the gaps between adjacent myelin segments. o Here, sodium channels are concentrated  In Myelinated axons = conducted PASSIVELY – instantly and decrementally – along the first segment of myelin to the next node of Ranvier. o Signal “jumps” along the axon from node to node. The Velocity of Axonal Conduction  Speed of action potentials depend on 2 properties: (1) diameter of axons, and (2) myelination o APs are faster in large-diameter axons o APs are faster in myelinated axons  The maximum velocity of conduction in human motor neurons is about 60 m/sec Conduction in Neurons without Axons  Many neurons in mammalian brains either do not have axons or have very short one o do not normally display action potentials.  Conduction in these interneurons is typically passive and decremental LO 4.8 The Hodgkin-Huxley Model in Perspective  Hodgkin-Huxley model – major advancement in our understanding of neural conduction  Based on the study of squid motor neurons, BUT these properties make it difficult to apply directly to mammalian brains (not all neurons are motor neurons).  5 Differences between cerebral neurons and motor neurons o Many cerebral neurons fire continually even when they receive no input o Axons of some cerebral neurons can actively conduct both graded signals and APs o APs of different classes of cerebral neurons vary greatly in duration, amplitude, and frequency o Many cerebral neurons do not display APs o The dendrites of some cerebral neurons can actively conduct APs SYNAPTIC TRANSMISSION: CHEMICAL TRANSMISSION OF SIGNALS AMONG NEURONS LO 4.9 Structure of Synapses  Axodendritic synapses – synapses of axon terminal buttons on dendrites o Terminate on dendritic spines – nodules of various shapes that are located on the surfaces of many dendrites.  Axosomatic synapses – synapses of axon terminal buttons on somas (Cell bodies)  Dendrodendritic synapses – capable of transmission in either direction  Axoaxonic synapses – mediate presynaptic facilitation and inhibition o Advantage: can selectively influence one particular synapse rather than the entire presynaptic neuron  Directed synapses – synapses at which the site of neurotransmitter release and the site of neurotransmitter reception are in close proximity

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Chapter 4 – Neural Conduction and Synaptic Transmission 

Nondirected synapses – site of release is at some distance from the site of reception o E.g. “string of beads” synapses – neurotransmitter molecules are released from a series of varicosities (bulges or swellings) along the axon and its branches

LO 4.10 Synthesis, Packaging, and Transport of Neurotransmitter Molecules  2 basic categories: (1) several small neurotransmitter, and (2) one large type of neurotransmitter (called neuropeptides aka short proteins)  Neuropeptides – short amino acid chain composed between 3-36 amino acids  Coexistence – the presence of more than one neurotransmitter in the same neuron. Small-molecule neurotransmitters Neuropeptides (Large-molecule) - Synthesized in the cytoplasm of the - Assembled in the cytoplasm of the cell terminal button body on ribosomes - Packaged in synaptic vesicles by the - Packaged in vesicles by the cell body’s Golgi complex button’s Golgi complex. - Vesicles are stored in clusters next to the - Transported by microtubules to the presynaptic membrane terminal buttons – 40 cm/day - Released into directed synapses and to - Vesicles are larger, and do not cluster near activate either ionotropic or metabotropic the presynaptic membrane receptors – ion channels - Released diffusely, and virtually all bind to metabotropic receptors that act on second messengers. LO 4.11 Release of Neurotransmitter Molecules  Exocytosis – the process of neurotransmitter release  The presynatic membrane is rich in voltage-activated calcium channels – these open when stimulated by an action potential  entry of Ca2+ ions causes synaptic vesicles to fuse with the presynaptic membrane and empty their contents into the synaptic cleft.  Exocytosis of small-molecule  released in a pulse each time an AP triggers a momentary influx of Ca+2 ions through the presynaptic membrane  Exocytosis of neuropeptides  released gradually in response to general increase in the level of intracellular Ca2+ ions; general increase in the rate of neuron firing.

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Chapter 4 – Neural Conduction and Synaptic Transmission

LO 4.12 Activation of Receptors by Neurotransmiter Molecules  Receptors – proteins that contain binding sites for particular neurotransmitters; located on the postsynaptic membrane.  Ligand – any molecule that binds to another  Receptor subtypes – the different types of receptors to which a particular neurotransmitter can bind; enable 1 neurotransmitter to transmit different kinds of messages Ionotropic Receptors  Associated with ligand-activated ion channels  Ion channel usually opens or closes immediately  induces an immediate postsynaptic potential  Example: EPSPs (depolarization) occurs because neurotransmitter opens sodium channels and increases the flow of Na+ ions into the neuron. Metabotropic Receptors  Associated with signal proteins and G proteins  Effects are slower to develop, longer lasting, more diffuse, and more varied  Attach to a serpentine signal protein that winds its way back and forth through the cell membrane 7 times – receptor outside the neuron and G protein inside the neuron.  2 Things can happen when a neurotransmitter binds to a MB receptor o Subunit moves along and bind to an ion channel – induces EPSP or IPSP o Trigger the synthesis of a chemical called the second messenger – diffuses through the cytoplasm and influence the activities of the neuron in a variety of ways.  Autoreceptors – have 2 characteristics o Bind to their neuron’s OWN neurotransmitter molecule o Located on the presynaptic (rather than the postsynaptic) LO 4.13 Reuptake, Enzymatic Degradation, and Recycling  2 mechanisms to terminate synaptic messages  Reuptake by transporters o More commmon; majority of neurotransmitters are drawn back through this method  Enzymatic Degradation o Other neurotransmitters are degraded in the synpase by the action of enzymes  Enzymes – proteins that stimulate or inhibit biochemical reactions, w/out being affected by them. o Example: acetylcholine is broken down by the enzyme acetylcholinesterase

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Chapter 4 – Neural Conduction and Synaptic Transmission LO 4.14 Glia, Gap Junctions, and Synaptic Transmission  Gap junctions – narrow spaces between adjacent cells that are bridged by fine, tubular, cytoplasmfilled protein channels – called connexins. o Connect the cytoplasm of two adjacent cells, allowing electrical signals and small molecules to pass from one cell to the next o AKA electrical synapses – transmit signals more rapidly than chemical synapses  Recent research  glial cells (especially astrocytes) and gap junctions play major role in brain function. Many gap junctions link astrocytes together in glial networks.  Unlike neurons, astrocytes are distributed evenly  each astrocyte has a greate potential to coordinate activity  coordinating the activity of synapses in its domain.  Tripartite synapse = the hypothesis that synaptic transmission depends on communciation among 3 cells (presynaptic neuron, postsynaptic neuron, and astrocyte) LO 4.15 Overview of the Neurotransmitter Classes  3 classes of small-molecule neurotransmitters: o (1) The amino acids, (2) the monamines, (3) the acetylcholine o There’s also a 4th class – unconvential neurotransmitters  1 class of large-molecules – the neuropeptides LO 4.16 The Roles and Functions of Neurotransmitters AMINO ACID NEUROTRANSMITTERS  Vast majority of fast-acting, directed synapses in CNS are amino acids  4 widely studied: o (1) glutamante, (2) aspartate, (3) glycine, and (4) GABA (gamma-aminobutyric acid) o First 3 are common in proteins we consume o GABA is synthesized by modification of glutamate  Glutamate = most prevalent EXCITATORY neurotransmitter  GABA = most prevalent INHIBITORY neurotransmitter MONOAMINE NEUROTRANSMITTERS  Each is synthesized from a single amino acid – hence monoamine (one amine)  Slightly larger than amino acid; effects tend to be more diffuse  Located usually in the brain stem (In small groups of neurons) o These neurons have axons with varicosities  4 types: (1) dopamine, (2) epinephrine, (3) norepinephrine, and (4) serotonin  There are subdivided into 2 groups o Catecholamines = synthesized from the amino acid tyrosine  Dopamine, epinephrine, norepinephrine  Noradrenergic = neurons that release norepinephrine  Adrenergic = neurons that relase epinephrine o Indolamines = synthesized from the amino acid tryptophan  Serotonin ACETYLCHOLINE  Created by adding an acetyl group to a choline molecule  Located an neuromuscular junctions, at many of the synapses in the ANS, and at synapses in several parts of the CNS  Broken down by the enzyme acetylcholinesterase

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Chapter 4 – Neural Conduction and Synaptic Transmission  Cholinergic = neurons that release acetylcholine UNCONVENTIONAL NEUROTRANSMITTERS Soluble gases - Includes nitric oxid and carbon monoxide - Produced in the neural cytoplasm and immediately diffuse into the extracellular fluid and then into nearby cells. - Stimulates production of a second messenger inside the cell. - Difficult to study becaue they exist only for a few seconds.

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Endocannabinoids Includes anandamide Similar to THC, the main psychoactive constituent of marijuana Produced immedately before they are released Synthesized from fatty compounds in the cell membrane Tend to be released from the dendrites and cell body Most of their effects on presynaptic neurons – inhibitng subsequent synaptic transmission.

NEUROPEPTIDES  Pituitary peptides – contains neuropeptides that were first identified as hormones released by the pituitary  Hypothalamic peptides – containes neuropeptides that were first identified as hormones released by the hypothalamus  Brain-gut peptides – contains neuropeptides that were first discovered in the gut  Opioid peptides – containes neuropeptides that are similar in structure to the active ingredients of opium  Miscellaneous peptides – the one that doesn’t fit in the others. PHARMACOLOGY OF SYNAPTIC TRANSMISSION AND BEHAVIOR  Agonists = drugs that facilitate the effects of a particular neurotransmitter  Antagonists = drugs that inhibit the effects of a particular neurotransmitter o Receptor blockers – bind to postsynaptic receptors without activating them, and block the access of the usual neurotransmitter LO 4.17 How Drugs Influence Synaptic Transmission 1) Synthesis of the neurotransmitter 2) Storage in vesicles 3) Breakdown in the cytoplasm of any neurotransmitter that leaks from the vesciples 4) Exocytosis 5) Inhibitory feedback via autoreceptors 6) Activation of postsynaptic receptors

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Chapter 4 – Neural Conduction and Synaptic Transmission 7) Deactivation LO 4.18 Behavioral Pharmocology: 3 Influential Lines of Research WRINKLES AND DARTS: DISCOVERY OF RECEPTOR SUBTYPES  Originally assumed that there was 1 receptor to each neurotransmitter; BUT NO  Research on acetylcholine receptors – can bind to either nicotine or muscarine  Nicotinic and muscarinic receptors are distributed differently in the NS o PNS = nicotinic receptors occur at the junctions b/w motor neurons and muscle fibers  Nicotinic receptors are ionotropic o ANS = muscarinic receptors located here  Muscarnic receptors are metabotropic  Examples of antagonists o Atropine – main ingredient of belladonna; receptor blocker that exerts its antagonist effect by binding to muscarinic receptors – blocks effects of acetylcholine o Curare – an extract of certain woody vines; deadly  Receptor blocker at cholinergic synapses (like atropine)  Acts at nicotinic receptors – binds to them and blocks transmission at neuromsuclar junctions – paralyzes recipients o Botox – neurotoxin released by a bacterium often ofound in spoiled food  Another nicotinic antagonist  Blocks the release of acetylcholine at neuromuscular junctions and is thus a deadly poison. PLEASURE AND PAIN: DISCOVERY OF ENDOGENOUS OPIOIDS  1970s = opioid drugs such as morphine bind effectively to receptors in the brain o Found in the hypothalaus and other limbic areas; most concentrated in the periaqueductual gray (PAG) – can produce strong analgesia (painkiller)  Existence of opioid receptors  opioid chemicals occur naturally in the brain  Endogenous – occuring naturally in the body  Enkephalins (“in the head”) – first endogenous opioid to be discovered  Endorphines – the second to be discovered  All endogenous opioid neurotransmitters are neuropeptides! Receptors are metabotropic TREMORS AND MENTAL ILLNESS: DISCOVERY OF ANTISCHIZOPHRENIC DRUGS  Breakthroughs in Schizophrenia; 2 findings  o Parkinson’s disease is associated with the degeneration of a main dopamine pathway in the brain o Dopamine agonists – cocaine and amphetamines – produce a transient condition that resembles schizophrenia called by excessive activity at dopamine synapses  Potent dopamine antagonists would be effective treamtment