* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Review (11/01/16)
Activity-dependent plasticity wikipedia , lookup
Apical dendrite wikipedia , lookup
Neuroregeneration wikipedia , lookup
Electrophysiology wikipedia , lookup
Single-unit recording wikipedia , lookup
Endocannabinoid system wikipedia , lookup
Neural oscillation wikipedia , lookup
Neurotransmitter wikipedia , lookup
Mirror neuron wikipedia , lookup
Perception of infrasound wikipedia , lookup
Biological neuron model wikipedia , lookup
Multielectrode array wikipedia , lookup
Axon guidance wikipedia , lookup
Nonsynaptic plasticity wikipedia , lookup
Development of the nervous system wikipedia , lookup
Synaptogenesis wikipedia , lookup
Anatomy of the cerebellum wikipedia , lookup
Chemical synapse wikipedia , lookup
Microneurography wikipedia , lookup
Caridoid escape reaction wikipedia , lookup
Central pattern generator wikipedia , lookup
Molecular neuroscience wikipedia , lookup
Premovement neuronal activity wikipedia , lookup
Neural coding wikipedia , lookup
Neuroanatomy wikipedia , lookup
Nervous system network models wikipedia , lookup
Optogenetics wikipedia , lookup
Clinical neurochemistry wikipedia , lookup
Neuropsychopharmacology wikipedia , lookup
Pre-Bötzinger complex wikipedia , lookup
Stimulus (physiology) wikipedia , lookup
Circumventricular organs wikipedia , lookup
Feature detection (nervous system) wikipedia , lookup
11/01/16 What are some differences between rods and cones Rod and Cone Photoreceptors Rods: A. High Sensitivity B. Slow Response C. Monochromatic Cone Opsin Cones: A. Low Sensitivity B. Faster Responses C. Color Vision Be careful with the ones in boxes. If he asks a test question about differences in phototransduction between rods and cones, C is not an answer. Color vision comes from having multiple cones that preferentially respond to different wavelengths. Photocurrent (pA) Comparison of Rod and Cone Physiology CONE ROD 0 0 -5 -20 -10 -40 -15 0 4 8 12 0 4 t (s) 8 12 t (s) ROD CONE Normalized Response 1.0 0.5 0.0 1 10 2 10 3 10 PIGM* / cell 4 10 5 10 Which ion is important for adaptation in photoreceptors Which ion is important for adaptation in photoreceptors • It is always calcium – We will talk about why/how next week Calcium and Photoreceptor Adaptation Baylor 1996 Light Adaptation Reduces Cone Sensitivity Dark 1.0 8.8 X 103 0.8 R/Rmax 4.0 X 104 0.6 0.4 0.2 0.0 1 2 3 4 Log Light Intensity 5 6 Liu • Afferent fibers (from periphery to spinal cord) have their cell bodies in the _____ – Dorsal Root Ganglion (DRG) • These fibers have a ______ geometry/morphology – Pseudounipolar • Pseudounipolar means______ – The axon spilts at the soma and goes in two directions. The cell body is in the DRG, the axon splits, one goes to the periphery, one goes into the dorsal horn of the spinal cord • Nociceptive fibers, also called ___-fibers, lack _____ and have a _____ diameter. As a consequence, the conduction velocity of these fibers is _____. – C-fibers Myelin Small Slow (~1 m/s) • Which of the A-fibers can also be considered nociceptive? – A-delta • Starting from a pinprick on the skin of your hand, describe the circuit that leads to withdrawal of the hand. • Rank the following in order of conduction velocity. Fastest to slowest – – – – A-delta A-Beta C A-alpha • Alpha, beta, delta, C • Would you have to change your answer if she asked you to order them based on axon diameter? – No. The fast ones have larger axon diameters than the slow ones, just as you would expect. • Which fibers are associated with the initial, “sharp” response to a painful stimulus and which are associated with “second pain”, the slower component that sticks around for a while after the painful stimulus. – A-delta sharp response – C second pain • What does WDR stand for? – Wide dynamic range. • What does that mean? These neurons respond to a wide range of stimulus strengths and their response is dynamic (the response changes in proportion to the strength of the stimulus). • What are the synaptic targets of A-delta and C fibers? A. nociceptive-specific neurons B. wide-dynamic range neurons C. Both of them D. None of them • What are the synaptic targets of A-delta and C fibers? A. nociceptive-specific neurons B. wide-dynamic range neurons C. Both of them D. None of them • What is windup • In the central sensitization "wind-up", which statements are true? A. In addition to glutamate, the release of substance P by C fibers also plays an important role in wind-up. B. The activation of NMDA leads to the opening of AMPA-R C. wind-up causes an increased sensitivity of the nociceptive-specific neurons, which now fire action potentials more readily D. Wind-up can persist long after an injury has healed • In the central sensitization "wind-up", which statements are true? A. In addition to glutamate, the release of substance P by C fibers also plays an important role in wind-up. B. The activation of NMDA leads to the opening of AMPA-R C. wind-up causes an increased sensitivity of the nociceptive-specific neurons, which now fire action potentials more readily D. Wind-up can persist long after an injury has healed • Please explain how a tissue injury causes thermal allodynia. These sensitize TRPV1 channels or upregulate their expression. TRPV1 channels are temperature sensitive. • Please explain how a tissue injury causes a thermal allodynia. • Answer: Tissue injury leads to the release of inflammatory molecules, such as bradykinin and prostaglandins, which sensitize TRPV1 channel. In addition, nerve growth factor NGF secreted from immune cells can increase the expression of TRPV1 channels (more channels on membrane), and enhance the thermal sensitivity of nociceptive neurons. • Under chronic pain conditions A. B. Nociceptive neurons adapt and respond less strongly to stimuli Sensitize and respond more strongly to a stimulus. B • What happens to ion channels during this process – • What is the difference between allodynia and hyperalgesia – • More excitatory, fewer inhibitory (through modulation or through change in expression at membrane). Lowers response threshold Hyperalgesia is a stronger pain response to a stimulus that is always painful. Allodynia is responding to a stimulus that is normally not painful as though it were painful. What kinds of transmitter-like things are associated with sensitization? – Neuropeptides choose excitatory or inhibitory • According to the gate control theory of pain, large-diameter fibers make _____ connections onto WDR neurons and small-diameter (nociceptive) neurons make _____ connections onto WDR neurons. • According to the gate control theory of pain, large-diameter fibers make _____ connections onto inhibitory interneurons and small-diameter (nociceptive) neurons make _____ connections onto inhibitory interneurons. choose excitatory or inhibitory • According to the gate control theory of pain, large-diameter fibers make excitatory connections onto WDR neurons and smalldiameter (nociceptive) neurons make excitatory connections onto WDR neurons. • According to the gate control theory of pain, large-diameter fibers make excitatory connections onto inhibitory interneurons and small-diameter (nociceptive) neurons make inhibitory connections onto inhibitory interneurons. • If only large-diameter fibers are activated, inhibitory interneurons are ________, which means they _______ the pain pathway, so you _______ experience pain, because ________. • If only small-diameter fibers are activated, inhibitory interneurons are _______, which means they ________ the pain pathway, so you _____ experience pain, because ______. Answers: see her slide if you find the words confusing. The diagram is easier to follow • If only large-diameter fibers are activated, inhibitory interneurons are activated, which means they inhibit the pain pathway, so you will not experience pain, because even though the large-diameter fibers are excitatory and excite the pain pathway, this is countered by the inhibtion that they also activate. • If only small-diameter fibers are activated, inhibitory interneurons are inhibited, which means they do nothing to the pain pathway, so you will experience pain, because there is no inhibition and the smalldiameter fibers will activate the pain pathway. • What are the three itch coding models? – Intensity – Labeled-line – Occlusion • Describe each – Intensity – same neurons carry information about both pain and itch. The perception of pain vs itch just depends on the strength (firing rate) of the response of the neurons carrying this information. – Labeled-line – separate pathways (neurons). There are neurons that only sense itch and others that only sense pain. – Occlusion – There are neurons that code for pain and others that code for itch and pain (labeled-line like), but in the presence of significant pain and itch, the pain response is more significant and occludes(inhibits) the itch neurons. • Which is the favored model – Occlusion Bagnall • Name two modalities/types of information that influence vestibular nucleus neurons besides vestibular sensation. • Name two modalities/types of information that influence vestibular nucleus neurons besides vestibular sensation. – Vision – Proprioception • Many neurons in the vestibular circuit operate around high baseline firing rates as discussed in lecture. What do you think are the advantages of this feature? What are some disadvantages? Vestibular sensation: your sixth sense ...doesn’t include interoceptive senses: vestibular, proprioceptive Vestibular end-organs come in two flavors Otoliths saccule, utricle I would know that there are two otoliths Vestibular end-organs come in two flavors Semicircular canals superior, posterior, horizontal I would know that there are 3 semicircular canals Otoliths report head translation...and gravity The saccule and utricle contain a gel-like mesh with suspended crystals (otoconia). Both contain hair cells with two dominant orientations. I would know how otoliths work in 3d even though there are only two In response to accelerative forces, this gel slides in the corresponding direction, opening some hair cells and closing others. Scarpa’s ganglion contains cell bodies of 8th nerve neurons. • Signals processed by the otolith and semicircular canal end-organs differ in which of the following ways? Circle all that apply. a) Hair cells innervating an otolith are all aligned in the same direction, whereas those innervating a semicircular canal have mixed orientations. b) Hair cells innervating a semicircular canal are all aligned in the same direction, whereas those innervating an otolith have mixed orientations. c) Afferents innervating semicircular canals have low baseline firing rates, but those innervating otoliths have high firing rates. d) Both otoliths and semicircular canals report head translation. e) Semicircular canals provide a transient signal about head rotation and cannot report gravity, unlike otoliths. • Signals processed by the otolith and semicircular canal end-organs differ in which of the following ways? Circle all that apply. a) Hair cells innervating an otolith are all aligned in the same direction, whereas those innervating a semicircular canal have mixed orientations. b) Hair cells innervating a semicircular canal are all aligned in the same direction, whereas those innervating an otolith have mixed orientations. c) Afferents innervating semicircular canals have low baseline firing rates, but those innervating otoliths have high firing rates. d) Both otoliths and semicircular canals report head translation. e) Semicircular canals provide a transient signal about head rotation and cannot report gravity, unlike otoliths. Crucial differences in end-organ function Semicircular canals Report head rotation Otoliths Report head translation Fluid eventually catches up movement only reported transiently Gel only returns to original position when forces let up; therefore, reports both gravity and translation Have single excitatory direction Have mix of hair cell orientations, not single direction Both are conveyed by nerve fibers with high baseline firing rates Which are recordings from otoloiths and which are from semicircular canals Spikes/s Firing of neurons innervating otoliths reports orientation Firing of neurons innervating canals reports rotation Sinusoidal stimulation J Neurophys 1971 a, b, c Vestibular and auditory afferents are really different Auditory nerves Much lower baseline firing rates Response to sound (pure tones) often involves phase locking: all spikes fired at particular phase of sound oscillation. Dreyer and Delgutte J Neurophys 2006 • Turning your head to the left (excites/inhibits) vestibular nucleus neurons on the left side of your head? • Which direction do your eyes move? Circuit of horizontal angular VOR Push-pull action: excitation from one side and inhibition (and decrease in excitation) from the other Straka and Dieringer 2004 • You implant a small micro-pump in a rat’s right medial vestibular nucleus (responsible mostly for horizontal VOR). You infuse a small amount of the glutamate receptor antagonist NBQX. Briefly, what do you predict will happen to the VOR when you rotate the animal back and forth on a turntable? You can draw results if you wish, but label everything. Circuit of horizontal angular VOR Push-pull action: excitation from one side and inhibition (and decrease in excitation) from the other Straka and Dieringer 2004 • You implant a small micro-pump in a rat’s right medial vestibular nucleus (responsible mostly for horizontal VOR). You infuse a small amount of the glutamate receptor antagonist NBQX. Briefly, what do you predict will happen to the VOR when you rotate the animal back and forth on a turntable? You can draw results if you wish, but label everything. • NBQX decreased firing in the right MVN failure to make VOR to the left, AND an exaggerated VOR to the right due to loss of commissural inhibition. Which would respond in each case and which would be suppressed Passive head motion Active head motion Vestibular afferents Central vestibular neurons In 1-2 sentences, provide a possible explanation for the source of suppression: • In 1-2 sentences, provide a possible explanation for the source of suppression: • Possible explanation: cerebellar inhibition of predicted signal, using motor command and/or proprioceptive information. It’s not known for sure so would accept other reasonable ideas. Passive and active head movement encoding This is a great paper. Read it for fun. https://courses.cit.cornell.edu/bionb4240/Documen ts/Holst_Mittelsteadt_1950_English.pdf Cullen 2011 Keeping neurons firing fast: crucial role of Kv3 Primary dissociated medial vestibular nucleus neurons Slower firing Faster firing (projection (GABAergic) neuron) Injecting action potential waveform during voltage clamp to isolate different currents flowing during a spike Faster-firing neuron has a narrower spike and a 2x larger Kv3 component Gittis et al. 2010, J Neurophys Tail currents: a read-out of open, non-inactivated channels With a long depolarization, Na currents inactivate With brief depolarization, fewer Na channels inactivate. Tail current (arrow) is measure of channels that were open (ie not inactivated) when the cell was repolarized. Keeping neurons firing fast: crucial role of Kv3 Primary dissociated medial vestibular nucleus neurons Slower firing Faster firing (projection (GABAergic) neuron) Injecting action potential waveform during voltage clamp to isolate different currents flowing during a spike Faster-firing neuron has a narrower spike and a 2x larger Kv3 component Artificially broadening the spike, mimicking TEA application to block Kv3, yields diminished Na current on subsequent spike. Tail current Gittis et al. 2010, J Neurophys • Vestib nu. neurons express the Ca-gated K channel known as SK. You apply a known agonist of SK channels while recording from a slice prep of vestib nu. neurons. – What is gain, in the cellular sense? The behavioral sense? – What do you expect to happen to the gain in the cell you’re recording when an SK agonist is applied? Vestibulo-ocular reflex (VOR) The VOR and its necessity were described by a physician whose inner ear had been severely damaged by excessive streptomycin therapy. He could read in bed only by bracing his head against the headboard; otherwise the printed page jumped with each heartbeat. When walking he was unable to recognize faces or read signs unless he stood still. https://kin450-neurophysiology.wikispaces.com/VOR Changing the input/output relationship (gain) Blockade of BK channels with iberiotoxin increased gain Step currents in slice preparation to measure cellular gain Bidirectional changes in gain with ambient [Ca] Smith et al 2002