Nervous system, Neurons, and History of the Brain
Nervous system, Neurons, and History of the Brain
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Date Created: 10/11/15
Chapter 3 Neurophysiology The Generation Transmission and Integration of Neural Signals Delgado used a remote control to electrically stimulate electrodes in the brains of people in an attempt to pinpoint the cause of a neurological disorder the study of life processes within neurons which are specialized to use electrical signals for communication Electrical within Chemicalbetween Kneej erk re ex O Sensory neurons in the muscle detect the hammer tap and send an action potential along their axons to the spinal cord 0 The action potential releases a neurotransmitter at the axon terminal to stimulate spinal motor neurons 0 The motor neurons send action potentials down their axons to release another neurotransmitter into the muscles 0 The muscles contract kicking your foot in the air All living cells are more negative on the inside than on the outside so we say they are Idifference in electrical charge between the inside and outside of the cell Of all of the electrically charged particles that a neuron contains a majority are negatively charged ions especially large protein anions that cannot exit the cell The rest are positively charged ions All of these ions are dissolved in the inside the cell and the surrounding the cell membrane Neuron is more negative on inside than outside A neuron at rest exhibits a characteristic Wdifference across the membrane of about 50 to 80 thousands of volt or The negative sign indicates the cell s interior is more negative than the outside tubelike pore that allows ions of a specific type to pass through the membrane 0 Some are gated O Selectively allow only potassium ions to cross the membrane Cell membrane exhibits because it allows some things to pass through but not others The resting potential of the neuron re ects a balancing act between two opposing forces that drive potassium ions in and out of the neuron O causes molecules of a substance to spread from regions of high concentration to regions of low concentration I Molecules move down their concentration gradient 0 arises from the distribution of electrical charges rather than distribution of molecules Charged particles exert electrical force on one another Positively charged K are attracted to the negative interior of the cell and anions are attracted to the positive outside and thus tend to leave the interior for the extracellular uid pump three sodium ions out of the cell for every two potassium ions pumped in this action results in the buildup of k ions outside the cell and Na outside the cell Eventually the opposing forces exerted by the K concentration gradient and by electrostatic pressure reach the the electrical charge that exactly balances the concentration gradient O This corresponds to the resting potential Action potentials arise at the axon hillock Two concepts important for understanding action potentials 0 an increase in the membrane potential neuron becomes more negative on inside and more positive on the outside 0 the reverse Decrease in the membrane potential Graded across the membrane get smaller as they spread away from the point of stimulation If a neuron reaches an sometimes referred to as a spike occurs An action potential is a rapid reversal of the membrane potential that momentarily makes the inside positive and the outside negative 0 This action potential requires active propagation either it fires at full amplitude or t doesn t fire at all Information is encoded by the changes in number of action potential rather than amplitude 0 With stronger stimuli more action potentials are produced but the size of each remains the same Many axons exhibit or electrical oscillations immediately following the spike The action potential is created by the sudden movement of sodium ions into the cell 0 Change is accomplished through the action of a I When cell membrane becomes depolarized to threshold levels the channel s shape changes opening the gate to allow sodium ions through 0 This happens as a process Once a few sodium ions enter the cell the membrane is further depolarized and more gated channels open 0 Positive charges in the neuron push potassium ions out aided by the opening of additional voltage gaged potassium channels I This restores resting potential 0 Kind of There is a limitation to the succession of action potentials The membrane is sometimes said to be or unresponsive to a second signal This is because the ions are on the wrong side of the membrane and therefore an action potential cannot be created Refractoriness has two phases 0 a brief period immediately following the production of an action potential no amount of stimulation can induce another action potential because the voltage gated sodium channels can t respond only strong stimulation well beyond threshold can produce 0 another action potential I K ions are still owing out so the cell is temporarily hyperpolarized after firing an action potential 0 The overall duration of the refractory phase is what determines a neuron s maximal firing rate Transmission of action potentials is limited to axons Ion channels on cell body and dendrites are stimulated chemically at synapses The action potential is regenerated down the length of the axon Axon conducts action potentials in only one direction O The action potential does not spread from the axon hillock back over the cell body and dendrites because the membrane there has very few voltage gated sodium channels so they cannot produce an action potential varies with the diameter of the axon 0 Larger axons allow the depolarization to spread faster through the interior 0 Not as fast as speed of light 0 Ensures rapid sensory and motor processing sheath speeds up conduction O Interrupted by small gaps spaced about every millimeter along the axon The myelin insulation resists the ow of ions across the membrane the action potential jumps from node to node This is called Invertebrates have unmyelinated neurons and thus have slower conduction results when the body makes antibodies that attack myelin and interfere with the action potential conduction which can have a devastating effect on brain function By producing different sorts of local graded potentials some synapses make the neuron more likely to reach threshold while others make it less likely Neurotransmitters brie y alter the membrane potential of the other cell 0 Called An excitatory presynaptic neuron causes it to produce an all or none action potential that s spreads to the end of the axonreleasing transmitter After a brief delay the postsynaptic cell displays a small local depolarization as sodium channels open to let the positive ions in this postsynaptic membrane depolarization is known as an because it pushes the postsynaptic cell a little closer to the threshold for action potential Generally the combined effect of many excitatory synapses is needed to elicit an action potential in a postsynaptic neuron A re ects the time needed for the neurotransmitter to be released diffuse across the synaptic cleft and affect the postsynaptic cell The action potential of the inhibitory presynaptic neuron looks exactly like that of the excitatory presynaptic neuron All neurons use the same kind of action potential When the inhibitory presynaptic neuron is activated the postsynaptic membrane potential becomes even more negative or hyperpolarized 0 Usually results from the opening of channels that permit chloride ions to enter the cell I Make membrane potential more negative because they rush in because they are highly concentrated outside the cell Neurons perform information processing by using a sort of neural algebra The depolarization and neuron potential of a postsynaptic neuron depends on the subtraction of ESPs and ISPs 0 Relative sum is also in uenced by distance summation of potentials originating from the different physical locations across the cell body the postsynaptic potentials last a few milliseconds before fading away and the closer they are in time the greater is the overlap and more complete is the summation Dendrites expand the receptive surface of the neuron and increase the amount of input the neuron can handle I When a potential arises at the dendritic spine its effect is even smaller because it has to spread down the shaft of the spine 0 Thus information arriving at various parts of the neuron is weighted in terms of the distance to the axon hillock and the path of resistance along the way 0 Steps in chemical synaptic transmission 0 The action potential arrives at the presynaptic terminal 0 Voltagegated calcium channels in the membrane of the axon terminal open and calcium ions enter the axon terminal 0 Calcium ions cause synaptic vesicles to fuse with the presynaptic membrane and release the transmitter molecules into the synaptic cleft I Synaptic delay is caused by the time needed for calcium ions to enter the terminal for the transmitter to diffuse across the synaptic cleft and for transmitter molecules to interact with their receptors 0 Some transmitter molecules bind to receptor molecules in the postsynaptic membrane leading to the opening of ion channels in the posynaptic membrane The resulting ow of ions creates a local EPSP or IPSP in the postsynaptic neuron O The ipsps and epsps in the postsynaptic cell spread toward the axon hillock if depolarizes enough action potential will arise O Synaptic transmission is rapidly stopped O Synaptic transmitter may also activate presynaptic receptors resulting in a decrease in transmitter release 0 The rate of making the transmitter is regulated by the enzymes that are manufactures in the neuronal cell body and transported actively down the axons to the terminals 0 Key and locks analogy for the connection of transmitter on a receptor protein 0 can fit into a transmitter and activate or block it I Ex fits into ligandbinding site in neurotransmitter molecules located in the postsynaptic membrane I At excitatory synapses Ach opens channels for sodium and potassium ions At inhibitory synapses Ach opens channels for chloride ions 0 this idea is strengthened by the fact that various chemicals can fit onto receptor proteins and block the entrance of the key I ex is one that block Ach receptors 39 Scis I Nicotine mimics Ach at some synapses increasing alertness and heart rate I Ach acts on at least four subtypes o receptors 0 Each subtype of neurotransmitter receptor has a unique pattern of distribution within the brain 0 The number of any type of receptor remains plastic in adulthood 0 it is important that each activation of the synapse be fried in order to maximize how much information can be transmitted 0 two processes bring transmitter effects to prompt halt O transmitter molecules can be rapidly broken down and thus inactivated by special enzymes The enzyme that inactivates ACH is AChE I breaks it down into products that are used to make more ACH in the axon terminal O transmitter molecules may be swiftly cleared from the synaptic cleft by being absorbed back into the axon terminal that released them Norepinephrine dopamine and serotonin are examples of neurotransmitters whose activity is terminated mainly by reuptake I Special receptors for the transmitter called are located on the presynaptic terminal I Conserve resources on axons often near the terminal allowing the presynaptic neuron to strongly facilitate or inhibit the activity of the postsynaptic axon Neurons may form contacts allowing coordination of their activities 0 Several factors account for the speed of the knee jerk re ex 0 Both sensor and the motor axons involved are myelinated and of large diameter 0 Sensory cells synapse directly on the motor neurons 0 Both the central synapse and the neuromuscular junction are fat synapses I provide useful information about the activity of brain regions during behavioral processes I are EEG responses to a single stimulus such as a ash of light or a loud sound 0 Can be used to detect hearing problems in babies I accompanied by when the person suddenly looses consciousness with muscles tensed and then falls to the ground as the body rhythmically convulses for seconds to minutes 0 Disorder of electrical impulses in the brain 0 During a seizure there is widespread synchronization of electrical activity broad stretches of the brain start firing simultaneously 0 major seizures involving loss of consciousness O characteristic spike and wave EEG activity evident for 515 seconds I Cannot recall the events that occurred 0 do not involve the entire brain and can produce a wide variety of symptoms I Often preceded by an unusual sensation or aura I In some patients these may be provoked by stimuli such as loud sounds and ashing lights 0 Antiepileptic drugs tend to selectively reduce the excitability of neurons 0 Usually begins in one part of the brain and then spreads to others 0 The brain function is organized in a map that reproduces body parts 0 Areas especially sensitive to touch are regulated by a relatively large area of cortex compared to somewhere else 0 Our mind is a result of physical processes at work in the machine we call the brain Chapter 4 The Chemistry of Behavior 7892 I substances from external sources 0 Used to try and change the functioning of peoples bodies and brains I A presynaptic neuron releases and a substance from an internal source I when the vesicles fuse with the synaptic membrane and release the neurotransmitter 0 Two basic kinds of neurotransmitter receptors 0 quickly change their shape to open or close their ion channel O don t contain ion channels Link across the cell membrane to complicated chemical machinery inside the postsynaptic neuron Alter the inner workings of the postsynaptic cell using a system called second messengers to cause changes in excitability or other slower largescale responses I Ex May kick off a chain of reactions that will effect gene expression 0 A substance is a neurotransmitter if 0 It can be synthesized by presynaptic neurons and stored in axon terminals 0 It is released when action potentials reach the terminals 0 It is recognized by specific receptors located on the postsynaptic membrane 0 It causes changes in the postsynaptic cell 0 Blocking its release interferes with the ability of the presynaptic cell to affect the postsynaptic cell AMINES Quaternary amines Acetylcholine ACh Monoamines Catecholamine s Norepinephrine NE epinephrine adrenaline dopamine DA Indolemines serotonin5HT melatonin AMINO ACIDS Gammaaminobutyric acid GABA glutamate glycine histamine NEUROPEPTIDES Opioid Peptides Enkephalins metenkephalin leuenkephalin Endorphins betaendorphin Dynorphins dynorphin A Other neuropeptides Oxytocin substance P cholecystokinin CCK basopressin neuropeptide Y NPY hypothalamicreleasing hormones GASES Nitric oxide carbon monoxide 0 Because they are involved in a wide range of disorders parkinsons schizophrenia alzheimers and depression anime neurotransmitter mechanisms are a major target for drug development 0 Acetylcholine O Cholinergic ACH containing neurons are found in nuclei within the basal forebrain 0 Dopamine 0 Important for aspects of behavior 0 Mesostriatial pathway originates in and around the substantia nigra of the midbrain From there axons project to parts of the basal ganglia I When people lose a significant amount of dopaminergic neurons they develop profound movment problems of Parkinson s disease 0 The mesolimbocortical pathway originates in the midbrain in a region called the The pathway projects to areas in the limbic system and cortex I Important in the perception of reward I Abnormalities are associated with symptoms of schizophrenia I Also seems important for addictive behaviors 0 There are very few serotonergic neurons just 200000 or so Neurons originate from the midline of the midbrain and brainstem in the O Serotonin participates in the control of behaviors including mood vision sexual behavior anxiety sleep and many other functions 0 Drugs that mimic serotonin like Prozac cause serotonin to accumulate and are often effective for relieving depression and anxiety Noradrenergic neurons have their cell bodies in two regions of the brainstem and midbrain The O Axons project into the cerebellum and the cortex limbic system and thalamic nuclei 0 Participate in the control of behavior ranging from alertness to mood to sexual behavior Some amino acids act as neurotransmitters 0 Most common 0 Excitatory glutamate I Interacts with the NMDA receptor 0 Memory formation 0 Inhibitory GABA I Anxiety relief I Ionotrpic and allow CL to ow into the postsynaptic membrane thus inhibiting that cells activity I Drugs that mimic it tend to be calming agents because they decrease neural activity 0 Benzodiazepines O Valium and Ativan Many peptides function as neurotransmitters O Opioid peptides endogenous peptides that mimic wellknown exogenous opiate drugs such as opium morphine and codeine I Act in the brain to reduce our perception of pain Some neurotransmitters are gases 0 Different in three ways I Gas transmitters are produced outside axon terminals especially in the dendrites and are not held in vesicles the substance simply diffuses out of the neuron as it is produced I No receptors in the membrane of the target cell are involved Instead the gas transmitter diffuses into the target cell to trigger second messengers inside I Function as by diffusing from the postsynaptic neuron back to the presynaptic neuron the gas transmitter conveys information that is used to physically change the synapse I May be crucial for memory formation Any substance that binds to a receptor is termed a The natural ligands for receptors are molecules of neurotransmitters of course 0 when bind to receptor they activate the receptor I Mimic effects of normal transmitters O do not activate it Block the receptor from being activated by normal transmitter The effects of a drug depend on its dose Chemical attraction of a drug to a receptor is known as 0 Once bound a drug has a certain propensity to activate the receptor its When plotted on a graph the relationship between drug doses and observed effects is called a 0 The amount of a drug that gets to the brain and how fast it gets there depends in part on the drugs route of administration 0 A drug is if it is free to act on the target tissue and not in use elsewhere or in the process of being eliminated 0 The duration of a drug also depends on how the drug is metabolized and excreted from the body I In some cases the metabolites of themselves are active this of drugs can produce substance With beneficial or harmful actions I Blood brain barrier presents a problem for neuropharmacology because many drugs that might be clinically useful are too large to pass the blood bran barrier to enter the brain I Once the body has been exposed to a drug it may change to counteract the drug s effectiveness This response is called in which a drug s effectiveness diminishes over repeated treatments 0 Some provoke in Which the body becomes more effective at eliminating the drug before it can have an effect Sometimes the target tissue itself may change its sensitivity to the drug I Often caused by a change in how many receptors are on the target cell 0 After repeated doses of an agonist drug neurons may their receptors decrease the number of available receptors to Which the drug can bind thereby countering the drug effect 0 If the drug is an antagonists target neurons may instead increase the number of receptors 0 Tolerance of a particular drug often generalizes to other drugs of the same chemical class this is called I Some drugs alter the presynaptic neuron 0 Three main categories I effects on transmitter production I effects on transmitter release I effects on transmitter clearance O presynaptic neuron uses to monitor how much neurotransmitter they have released I some drugs stimulate this and provide a false feedback signal 0 some drugs alter postsynaptic processes