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Block 3 NEUROPHYSIOLOGY Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  UNIT 9 Chapter 46: Organization of the Nervous System, Basic Functions of Synapses, and Neurotransmitters Slides by Thomas H. Adair, PhD...

Block 3 NEUROPHYSIOLOGY Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  UNIT 9 Chapter 46: Organization of the Nervous System, Basic Functions of Synapses, and Neurotransmitters Slides by Thomas H. Adair, PhD Copyright © 2021 by Saunders, an imprint of Elsevier Inc. Four lobes of cerebral cortex Frontal lobe: (higher mental functions) Anterior cerebral art. Middle cerebral art. Parietal lobe: (integrates sensory information from different modalities) Anterior cerebral art. Middle cerebral art. Temporal lobe: (auditory perception, semantics, memory) Middle cerebral art. Posterior cerebral art. Occipital lobe: (visual processing center – visual cortex) Middle cerebral art. Surface anatomy of brain Primary motor cortex Somatosensory cortex Cranial nerves Cranial nerves 75% of parasympathetic nerve fibers are in the vagus nerves. “Out Of Office Today Tomorrow And Friday And Got Verification So Hush” Organization of the nervous system Anatomical stuff Spinal cord Organization of Nervous System Sensory Division – tactile, visual, auditory, olfactory Integrative Division – process information, creation of memory Motor Division – respond to and move about in our environment Somatosensory Axis of Nervous System Figure 46-2 Skeletal Motor Nerve Axis of Nervous System Figure 46-3 3 Major Levels of CNS Function Spinal cord level Lower brain level Higher brain or cortical level  Spinal Cord Level The spinal cord level: – more than just a conduit for signals from periphery of body to brain and vice versa – cord contains: walking circuits withdrawal circuits support against gravity circuits circuits for reflex control of organ function  Lower Brain Level Contains: – medulla, pons, mesencephalon, hypothalamus, thalamus, cerebellum and basal ganglia Controls subconscious body activities: – arterial pressure, respiration, equilibrium, feeding reflexes, emotional patterns Higher Brain or Cortical Level Cortex never functions alone, always in association with lower centers. Large memory storehouse. Essential for thought processes. Each portion of the nervous system performs specific functions, but it is the cortex that opens the world up for one’s mind.  Neuron Structure 3 major components: Soma - main body of neuron. Axon - extends from soma to synaptic terminal. - the effector part of neuron. Dendrite - projections from soma. - the sensory portion of neuron. Figure 46-1  Anterior motor neuron Posterior horn receives sensory information. anterior root anterior horn Also called (anterior column or ventral horn) - contains motor neurons that affect axial muscles. Figure 45-6 Review of membrane potential Vm -65 0 mV EK -86 ECl -70 ENa +61 Fig 46-8 Electrotonic potentials Subthreshold potential change vs. action potential Recap: how membrane potential and excitability relate  Synaptic responses - EPSP Note the following: Presynaptic neuron no action potentials occurred in postsynaptic neuron because a threshold potential was not + Postsynaptic neuron achieved the excitatory post synaptic Presynaptic potential (EPSP) is an electrotonic neuron response that decays with an 0 exponential time course the last EPSP is larger because it mV ?Which channels and ions can create occurs an EPSP?before the previous EPSP -70 has decayed fully. threshold -60 Glutamate mV epsp opens cation channels -70 Postsynaptic chief excitatory transmitter 10 ms neuron in CNS ?What type of summation is With spatial summation, shown? EPSP’s created by distant synapses overlap. A single neuron can have more than one synaptic terminal Spatial summation can occur with a single presynaptic neuron.  Synaptic responses - IPSP Presynaptic neuron Note the following: The post-synaptic cell is hyperpolarized. - Postsynaptic neuron – Remember that hyperpolarization depresses excitability - inhibitory – This is an inhibitory post 0 synaptic potential (IPSP) IPSPs can summate too!! mV IPSPs result from increases in Presynaptic neuron ?Which ions are involved in -70 membrane permeability creating an IPSP? -60 mV Postsynaptic neuron GABA (γ-Aminobutyric acid), opens Cl- -70 channels. ipsp chief inhibitory transmitter in adult -80 CNS 10 ms could be an excitatory transmitter during development (because of Summation of Postsynaptic Potentials Spatial Summation excitation of a single presynaptic neuron on a dendrite will almost never induce an AP in the neuron. each terminal on the dendrite accounts for about a 0.5 - 1.0 mV EPSP. when multiple terminals are excited simultaneously the EPSP generated may exceed the threshold for firing and induce an AP.  Summation of Postsynaptic Potentials Temporal Summation A neurotransmitter opens a membrane channel for about 1 msec, but a postsynaptic potential (EPSP or IPSP) lasts for about 15 msec A second opening of the same membrane channel can increase the postsynaptic potential to a greater level. Therefore, the more rapid the rate of terminal stimulation, the greater the postsynaptic potential. Rapidly repeating firings of a small number of terminals can summate to reach the threshold for an AP. Electrotonic potentials EPSP = IPSP = Figure 45-9 Simultaneous firing of many synapses is required to reach threshold Often the summated postsynaptic potential is excitatory in nature but has not reached threshold levels. This neuron is said to be facilitated threshold because the potential is nearer the threshold for firing compared to the resting level, but not yet to the firing level. It is easier to stimulate this neuron with subsequent input. Figure 46-10  Facilitation at the squid giant synapse A Action 0.5 Ca++ concentration in Presynaptic synaptic end of neuron potentials Membrane 0.4 Amount of facilitation Potential (mV) 0.3 B Facilitation 0.2 Postsynaptic Membrane 0.1 EPSPs Potential (mV) 0.0 0 10 20 30 40 50 Interval between stimuli (ms) 0 10 20 30 Redrawn after Purves, Neuroscience. 5th ed., Sinauer, 2012. Time (ms) Facilitation: Definition – The increased transmitter release produced by an action potential that follows closely upon a preceding action potential. Note: This is not temporal summation. Mechanism – prolonged elevation of presynaptic calcium levels following synaptic activity. Function of Dendrites in Stimulating Neurons  Dendrites allow signal reception from a large spatial area providing opportunity for summation of signals from many presynaptic neurons.  Dendrites do not transmit action potentials. They have few voltage gated Na+ channels.  Dendrites transmit signals by electrotonic conduction. Transmission of current by Figure 46-11 conduction in the fluids of the dendrites. Special Characteristics of Synaptic Transmission Synaptic facilitation – enhanced responsiveness following repetitive stimulation. – mechanism is build-up of calcium ions in presynaptic terminals. – build-up of calcium causes more vesicular release of Synaptic fatigue (or short-term synaptic depression) transmitter. – excitatory synapses are repetitively stimulated at a rapid rate until rate of postsynaptic discharge becomes progressively less. – It’s a protective mechanism for excessive neuronal activity – Possible mechanism for causing epileptic seizure to end – Mechanism: See Reverberatory Circuit below. Synaptic delay – the process of neurotransmission takes time, from the time delay one can calculate the number of chemically connected series neurons in a circuit.  Actions of transmitter substances on postsynaptic membrane Ion channels: o Cation channels / Anion channels o Rapid response – short lived o Small molecule transmitters (ACh, NE, etc) Ach and NE also 2nd messenger system open ion channels o Multiple responses using a G protein o Prolonged responses 2nd messenger system. See o Neuropeptides Chapter 61. Synaptic transmission: ion channels Synaptic transmission: 2nd messenger Figure 46-7 Neurotransmitters: 2 main types 1. Small molecule, rapidly acting transmitters 2. Neuropeptides, slowing acting transmitters  Small molecule, rapidly acting transmitters Function: small molecule Usually excitatory in CNS transmitters mediate most acute responses of nervous system. GABA: Chief inhibitory transmitter in CNS Usually inhibitory Glycine: inhibitory transmitter, mainly in cord Glutamate: Chief excitatory transmitter in CNS. Accounts for >90% of the synaptic connections in CNS. Synthesized on demand; does not use vesicles – diffuses through membrane Table 45-1 What does this have to do with chicken eggs? 113 mg choline  Neuropeptides, slowing acting transmitters, GFs Act on Metabotropic receptors Cause long-term changes  Changes in number of neuron receptors Often co-released with small molecule  Long-term opening or closure of ion channels  Changes in number and sizes of synapses transmitters Some neurons make several different peptides Table 45-1 Environmental Changes and Synaptic Transmission Acidosis. – depresses neuronal activity. – diabetic coma – pH change from 7.4 to 7.0 usually will induce coma. Alkalosis. – increases neuronal excitability. – Can initiate petit mal seizure – pH change from 7.4 to 8.0 usually will induce seizures. Hypoxia. – brain highly dependent on oxygen – interruption of brain blood flow for 3 to 7 sec can lead to unconsciousness. Hyperventilation can trigger absence seizures Absence epilepsy (petit mal seizure) causes you to blank out or stare into space for a few seconds Often goes unnoticed Most common in children Typically, doesn’t cause long-term problems https://www.ncbi.nlm.nih.gov/pmc/articles/PMC654 6426/  UNIT 9 Chapter 47: Sensory Receptors, Neuronal Circuits for Processing Information Slides by Thomas H. Adair, PhD Copyright © 2021 by Saunders, an imprint of Elsevier Inc. Types of Sensory Receptors Mechanoreceptors - detect deformation Thermoreceptors - detect change in temperature Nociceptors - detect damage (pain receptors) Noci - is derived from the Latin Electromagnetic - detect light term for “hurt” Chemoreceptors - taste, smell, CO2, O2 etc. Types of Sensory Receptors Figure 47-1  Locations of skin sensory receptors in the fingertip Glabrous skin (non-hairy skin) Epidermis Dermis Subcutaneous layer Purves. Neuroscience. 5th ed, 2012. Figure 9.5  Sensation Each of the principal types of sensation: touch, pain, sight, sound, is called a modality of sensation. How the sensation is perceived is determined by the characteristics of the receptor and the central connections of the axon connected to the receptor. Specificity of nerve fibers for transmitting only one modality of sensation The labeled-line is called principle refers tothe the concept labeled linethat each receptor responds to a principle. limited range of stimuli and has a direct line to the brain.  What factors generate receptor potentials? Mechanical deformation - stretches the membrane and opens ion channels. Application of chemicals - also opens ion channels. Change in temperature - alters membrane permeability. Electromagnetic radiation - changes membraneNote permeability tostimuli that all these ions. lead to changes in membrane permeability to ions; this can cause either hyperpolarization or hypopolarization (i.e., depolarization).  Generation of receptor potential by mechanism distortion Mechanical distortion increases Na+ conductance causing a receptor potential. The receptor potential is an electrotonic potential. ? Why is there no AP Figure 47-3 except in the axon? Pacinian corpuscle Relationship between receptor potentials and action potentials - APs occur when receptor potential (green line) rises above threshold - Increased stimulus intensity causes increased receptor potential, which increases Figure 47-2 AP frequency.  Stimulus strength and receptor potential in Pacinian corpuscle Only larges changes in stimulus strength can be discerned when stimulus strength is high Small changes in stimulus strength can be discerned when stimulus strength is low This relationship allows receptors to have a wide range of response Figure 47-4 Adaptation of Receptors Figure 47-5 Adaptation of Receptors (cont.) Rate of adaptation varies with type of receptor. Adapted from Kandel, Schwartz And Jessell 4th addition 2000 Rapidl Slowly Rapidl Slowly y adapti y adapti adapti ng adapti ng ng ng Mechanism of Adaptation - varies with the type of receptor. Mechanoreceptors – fluid redistribution in Pacinian corpuscle decreases distorting force. Photoreceptors – the amount of light sensitive chemicals is changed.  Slowly Adapting (Tonic) Receptors Continue to transmit impulses to brain for long periods of time while stimulus is present. S Keep brain apprised of the status of the body with respect to its surroundings. Will adapt to extinction if stimulus is present but this may take hours or days. These receptors include muscle spindle, Golgi tendon apparatus, Ruffini endings, Merkel discs, Macula, pain, temperature, chemo- and baroreceptors.  Rapidly Adapting (Phasic) Receptors Respond only when change is taking place. S Rate and strength of response is related to rate and intensity of stimulus. Important for predicting future position or condition of body. Very important for balance and movement. Types of rapidly adapting receptors: Pacinian corpuscle, Meissner’s corpuscle, semicircular canals.  Slowly and rapidly adapting mechanoreceptors provide different Stimulus information Slowly adapting Slowly adapting receptors (aka, tonic receptors) - continue to respond to a 0 1 2 3 4 stimulus. Time (s) Rapidly Rapidly adapting receptors adapting (aka, phasic receptors) – respond only at the onset (and often the offset) of stimulation. 0 1 2 3 4 Time (s) Sensory Nerve Classification Transmission of receptor information to brain by different types of neurons Figure 47-6 Somatic sensory afferents that link receptors to CNS Purves. Neuroscience. 5th ed, 2012. Table 9.1 Importance of Signal Intensity Signal intensity is critical for the interpretation of An signals by the brain (e.g., example pain). of spatial summati on Gradations in signal intensity can be achieved by: 1) Spatial summation - increasing the number of fibers stimulated. 2) Temporal summation - increasing the rate of firing in a given number of fibers. Figure 47-7  Excitation and Facilitation Figure 47-9 Figure 47-10 Neuron ‘1’ excites neuron ‘a’, and facilitates neurons ‘b’ and ‘c’  Neuronal Pools Groups of neurons with special characteristics of organization. Comprise many different types of neuronal circuits. – converging – diverging – reverberating – inhibitory  Divergence in neuronal pathways Figure 47-11 Amplifying type of divergence. A signal is transmitted in two directions. For example, a single pyramidal cell in the motor cortex can Example: information from dorsal stimulate several hundred muscle columns of the spinal cord takes two fibers. directions: (1) cerebellum, (2) Convergence of multiple input fibers Figure 47-12 - Multiple terminals from a - Allows summation of single incoming fiber information from multiple terminate on the same sources. neuron. - Correlates, summates, and - Provides spatial sorts information. summation Inhibitory circuit excite no AP Figure 47-13 Important for controlling all antagonistic pairs of muscles… called the reciprocal inhibition circuit. Important in preventing over-activity in the brain Reverberatory or Oscillatory Circuits Output signals from reverberatory circuit after single input stimulus Hall, Guyton. Figure 47-15 A single input stimulus (1 msec) causes a prolonged output (msec to minutes). Caused by Positive feedback within the neuronal circuit (the input to the circuit is re-excited). Note: the circuit can be facilitated or inhibited What as shown. causes sudden cessation of reverberation? Figure 47-14 Reverberatory circuits (cont.) This is positive feedback - What stops fatigue of synaptic junctions it? What is the mechanism of fatigue? A. Transmitter depletion B. Receptor inactivation C. Abnormal ion concn in axon D. All of the above Control of synaptic sensitivity Underactivity leads to up- regulation of membrane receptors Overactivity leads to down- regulation of membrane receptors. ot all reverberatory circuits fatigue Shows continuous output from reverberating circuit that can be enhanced or suppressed ANS uses this type of information transmission to control vascular tone, gut tone, heart rate, etc. Figure 47-16  UNIT 9 Chapter 48: Somatic Sensations: I. General Organization, the Tactile and Position Senses Slides by Thomas H. Adair, PhD Copyright © 2021 by Saunders, an imprint of Elsevier Inc. assification of somatic sensations Mechanoreceptive - stimulated by mechanical displacement. Tactile: touch, pressure, vibration, tickle, itch Proprioceptive: static position, rate of change Thermoreceptive. detect heat and cold. Nociceptive. detect pain and any factor that damages tissue. Tactile receptors – small field Meissner corpuscles Location: non-hairy skin close to surface (fingertips, lips, eyelids, nipples and external genitalia). Function: motion detection, grip control Stimuli: skin motion, low frequency Meissner corpuscles Merkel discs vibration Merkel discs Adaptation: rapid adaptation Location: tip of epidermal ridges receptive field: 22 mm2 Function: form and texture perception type Aβ nerve fibers Stimuli: edges, points, corners, curvature Adaptation: slow adaptation receptive field: 9 mm2 type Aβ nerve fibers Purves. Neuroscience. 5th ed, 2012. Figure 9.5 Activity patterns recorded from mechanosensory afferents in fingertip Each dot is an action potential Small field, slow adaptation Larger field, fast adaptation Very large field, slow adaptation Huge field, very fast adaptation Purves. Neuroscience. 5th ed, 2012. Figure 9.6 Tactile receptors – large field Pacinian corpuscle (~ 1 mm) Location: dermis and deeper tissues Function: perception of distant events through transmitted vibrations; tool use Stimuli: vibration (250 Hz is optimal) Adaptation: Ruffini corpusclevery rapid Pacinian corpuscles adaptation Location: dermis Receptive Function: tangential force; field: entire hand finger or shape; hand type Aβ nerve motion detection fibers Stimuli: skin stretch Adaptation: slow adaptation receptive field: 60 mm2 type Aβ nerve fibers Purves. Neuroscience. 5th ed, 2012. Figure 9.5  Free nerve endings Free nerve endings (myelinated). Location: surface of body and elsewhere Function/stimuli: pain, temperature Adaptation: slow adaptation type Aδ nerve fibers, i.e., A-delta Free nerve endings (unmyelinated). Location: surface of body and elsewhere Function/stimuli: pain, temperature, itch Adaptation: slow adaptation type C Purves. Neuroscience. 5th ed, 2012. Figure 9.5  Pathways for the Transmission of Sensory Information Anterolateral Dorsal column- system medial lemniscal system Purves. Neuroscience. 5th ed, 2012. Figure 9.1B Almost all sensory information enters spinal cord through dorsal roots of spinal nerves. Two pathways for sensory afferents. Anterolateral system Dorsal column-medial lemniscal system  Dorsal Column-medial lemniscal System Contains large myelinated nerve fibers (30-110 m/sec). A-beta Three neurons to sensory cortex / decussates in medulla oblongata High degree of spatial orientation maintained throughout the tract. Transmits information rapidly and with a high degree of spatial fidelity (i.e., discrete types of mechanoreceptor information). Transmits touch, vibration, Figure 48-3  The Anterolateral System Contains smaller myelinated and unmyelinated fibers for slow transmission (0.5-40 m/sec). (A-delta, C) three neurons to sensory cortex / decussates in spinal cord low degree of spatial orientation. transmits a broad spectrum of modalities. pain, thermal sensations, crude touch and pressure, tickle and Figure 47-13  Dermatomes Dermatome – area of skin supplied by sensory neurons that arise from a spinal nerve ganglion. Clinical significance Localizing cord lesion Viruses such as varicella zoster hibernate in ganglia causing rash in associated dermatome. Referred pain (discussed later) Figure 48-14 Shingles follows the dermatome Years or decades after a chickenpox infection, the virus (varicella zoster virus) may break out of nerve cell bodies and travel down nerve axons to cause viral infection of skin associated with nerve. The rash occurs in the dermatome of the infected nerve cell.  The Somatosensory Cortex Located in the postcentral gyrus. Highly organized distinct spatial orientation. Each side of cortex receives information from opposite side of body. Unequal representation of the body. – lips have greatest area of Figure 48-6 representation followed by face and thumb. – trunk and lower body have least area of representation.  Sensory homunculus Homunculus – (latin) little human Figure 47-7  Brodmann’s areas Brodmann's areas show the cytoarchitectural organization of neurons (cell size, packing density, lamination) that he observed in the cerebral cortex using Nissl stain (1909). Figure 48-5 Figure 48-6 Somatosensory area 1 (primary somatosensory area) Brodmann’s areas: 1, 2, 3 Somatosensory association area Brodmann’s areas: 5,7  Lesions of somatosensory cortex Destruction of somatosensory area I causes: loss of vibration, fine touch, and proprioception. discrete localization ability. inability to judge the degree of pressure. inability to determine the weight of an object. inability to judge texture. Also: Hemineglect (unilateral neglect, hemispatial neglect or spatial neglect): Figure 47-7 patients are unaware of items to one side of space. Astereognosis: inability to recognize objects by touch Agraphesthesia: a disorientation of the skin’s sensation across its space (e.g., hard to identify a number or letter traced on the hand) Somatosensory association area Areas 5 and 7 in parietal area. Receives input from the somatosensory cortex, ventrobasal nuclei of the thalamus, and visual and auditory cortex. Function is to decipher complex sensory associations. Figure 48-5 Loss of these areas Figure 47-6 inability to recognize complex objects neglect of the contralateral world and even refusal to acknowledge the ownership of the contralateral body.  6 Layers of cerebral cortex Six separate layers of neurons with layer I near the surface of the cortex and layer VI deep within the cortex. Layer IV receives incoming signals and spread both up and down. Each column serves a specific sensory modality (i.e., stretch, pressure, touch). Layers I and II receive diffuse input from lower brain centers. Layers II and III neurons send axons to closely related portion of the cortex presumably for communicating between similar areas. Layer V and VI send axons to more distant parts of the nervous system, layer V to the brainstem and spinal cord, layer VI to the thalamus. Betz cells are giant pyramidal cells in layer V; they project directly onto the lower motor neurons in the spinal cord. Two-point discrimination The two-point discrimination threshold measures the minimum distance at which two stimuli are resolved as distinct; it reflects how finely innervated an area of skin is. The spatial resolution of stimuli on the skin varies throughout the body because the density of mechanoreceptors varies.  Lateral inhibition improves two- point discrimination Lateral inhibiti on Lateral inhibition is the present capacity of an excited neuron to reduce the activity of neighboring neurons; it improves the degree of contrast – Occurs at every synaptic level (for dorsal column system): dorsal column nuclei, ventrobasal nuclei of Figure 48-10 thalamus, cortex  UNIT 9 Chapter 49: Somatic Sensations: II. Pain, Headache, and Thermal Sensations Slides by Thomas H. Adair, PhD Copyright © 2021 by Saunders, an imprint of Elsevier Inc.  Pain Protective mechanism Occurs whenever tissue is being damaged. Causes individual to remove painful stimulus. two types of pain (fast pain and slow pain). fast pain (body surface) felt within 0.1 s after stimulus sharp pain: (knife cut, needle poke, burn). Not felt in most deeper tissues slow pain (body surface and deeper tissues) felt after 1 s or more throbbing or aching pain Usually associated with tissue destruction (bradykinin). Pain is perceived at 45◦ C at 45◦ C Pain is perceived Distribution curve obtained from large group of people showing minimal skin temperature that will cause pain Figure 49-1  Do females have a higher pain threshold than males? Pain perception threshold is the minimum amount of pain that evokes a report of pain. Pain tolerance threshold is reached when the subject acts to stop the pain. Males have higher pain perception threshold than females, and some studies show that males also have a higher pain tolerance threshold; another way of https://www.sciencedirect.com/science/article/pii/S15265 90023006077#:~:text=Clinical%20studies%20consistentl thinking, is that females show more sensitivity to pain. y%20find%20evidence,associated%20with%20female%2 0sex%20hormones. "It makes sense that the female reaction to pain would be stronger than that of a male since the female is more important to the survival of the species, especially if she cares for the young."  Ginger Genes and Anesthesia FROM THE LITERATURE Gingers (redheads) need about 20% more inhalation anesthetic to induce general anesthesia. They also need more local topical anesthetics, such as lidocaine or Novocain, which is why many redheads have a fear of dentists, according to the American Dentistry Association. The decreased sensitivity to anesthetics can be traced to mutations of the melanocortin-1 receptor gene (MC1R). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1362956/ HOWEVER, Gingers are more sensitive to opioids. Pain Receptors and Their Stimulation Pain receptors are free nerve endings Widespread in skin, arterial walls, joint surfaces, periosteum, falx and tentorium of cranial vault Lower density in internal structures Pain receptors do not adapt to the stimulus. Intensity of pain is correlated with rate of tissue damage (not total amount of damage). Extracts from damaged tissue cause pain when injected under skin. Bradykinin is main cause of pain resulting from tissue damage (slow pain). Also, potassium and proteolytic enzymes contribute.  Ischemia causes pain What is ischemia? What is hypoxia? Time course: arterial occlusion of limb causes pain in 15-20 s. Cause of ischemic pain. Lactic acid buildup Bradykinin Proteolytic enzymes  Dual Pain Pathways 1. Fast pain (first pain) a. transmitted by type A-delta fibers (velocity 6-30 m/sec). b. transmitted in neospinothalamic tract Because of these dual pathways, a double 2. Slow pain (second pain) sensation of pain often c. transmitted by type C fibers (0.5 - 2 m/sec). occurs: sharp pain d. transmitted in the paleospinothalamic tract. followed seconds later by slow pain. Ad fiber C fiber Subjective perception of pain 1st pain 2nd pain time  Neospinothalamic Tract Fast, sharp pain: A-delta fiber On entering cord, pain fibers may travel up or down 1- 3 segments and terminate on neurons in dorsal horn. Glutamate is excitatory transmitter of A-delta pain fiber nerve ending. Figure 49-2 2nd neuron crosses immediately to the opposite side and passes to the brain in the anterolateral columns. Some neurons terminate in the reticular substance but most go all the way to the ventrobasal complex of the thalamus. 3rd order neurons go to the cortex. Fast, sharp pain can be localized well when other tactile receptors are simultaneously stimulated. Figure 49-3  Paleospinothalamic Tract Slow, burning pain: C fiber Type C pain fibers terminate in laminae II & III of spinal cord. 2nd neuron crosses immediately to the opposite side and passes to the brain in the anterolateral columns. Substance P is excitatory transmitter of type C pain Figure 49-2 fiber nerve ending. Only 10 to 25 % of fibers terminate in thalamus. Most terminate diffusely in reticular nuclei of medulla, pons and mesencephalon; tectal area of mesencephalon; periaqueductal gray region. Poor localization of slow pain, often to just the affected limb or part of body. Figure 49-3  Substance P The P stand for “preparation” or “powder” Substance P is a peptide composed of 11 amino acids Thought to mediate lower back pain, arthritis, fibromyalgia. Over-the-counter creams containing capsaicin (made from chili peppers) can deplete Substance P from local nerve endings and relieve pain.  The Appreciation of Pain Removal of somatic sensory areas of cortex does not destroy the ability to perceive pain. Pain impulses to lower areas can cause conscious perception of pain. Therefore, cortex is probably important for determining the quality of pain. Stimulation of reticular areas of brain stem and intralaminar nuclei of thalamus (where pain fibers terminate) causes widespread arousal of the nervous system. Recall that C fibers that transmit slow pain terminate mainly in the reticular formation. What does this tell you? Ans. People with chronic slow pain cannot sleep. Endogenous Analgesia System Naloxone (aka, Narcan) is used to counter the effects of opiate overdose (heroin, morphine, etc) Naloxone is an opioid antagonist— meaning that it binds to opioid receptors and can reverse and block the effects of other opioids, such as heroin, morphine, and oxycodone. It's been called the Lazarus drug for its ability to revive people dying from overdoses. It can be injected or simply administered through a nasal spray. (The spray form of the drug is known by the brand name, Narcan.) Figure 49-04  Analgesia system of brain and spinal cord Electrical stimulation of the periaqueductal gray area relieves pain (and inhibits Somatic nociceptive projection neurons in the sensory dorsal horn of the cord). cortex Analgesic effects are mediated through 4 Amygdala brainstem sites shown. Hypothalamus These centers harbor multiple Anterolateral system transmitters that can both facilitate and Midbrain periaqueductal gray inhibit neurons in dorsal horn. Serotonin, from the Raphe nuclei Para- Medullary stimulates interneurons in dorsal column, brachial Reticular Raphe nuclei Locus coeruleus that, in turn secrete enkephalin. nucleus formation Enkephalin (an opioid peptide) can cause Dorsal horn of spinal cord both presynaptic and postsynaptic inhibition of incoming type C and type Aδ pain fibers where they synapse in dorsal horn. Higher centers can control pain Somatic sensory cortex Amygdala Hypothalamus Midbrain periaqueductal gray The placebo effect (Placebo means “I will please.”) Imaging studies: Placebo administration with expectation of an analgesic effect is associated with activation of opioid receptors in cortical and subcortical regions that are part of pain control system. Endogenous Opiate Systems Early 1970’s it was discovered that injection of minute quantities of morphine into area around third ventricle produced a profound and prolonged analgesia. This started the search for “morphine receptors” in the brain. Several “opiate-like” substances have been identified. Major endogenous opiates: beta-endorphin, met-enkephalin, leu-enkephalin, dynorphin. – Enkephalins and dynorphin - found in brain stem and spinal cord – Beta-endorphin - found in hypothalamus and pituitary Function of opiate system – Pain suppression during stress. – Response to emergency (reduction in responsiveness to pain). – Effective in defense, predation, dominance and adaptation to environmental challenges.  Gate theory of pain Stimulation of type A-beta fibers from peripheral tactile receptors can decrease transmission of pain signals. Gate is closed (and pain signal transmission to brain is attenuated) when A-beta fibers and C fibers are co- activated. Mechanism: a type of lateral inhibition of pain fiber by mechanosensory fiber. Probably the mechanism of action of massage, liniments, electrical stimulation of skin. Neuroscience. Purves et al, 2004. Figure 9.7B Audio-analgesia can reduce Pain and Suffering During Labor https://pubmed.ncbi.nlm.nih.gov/11991313/  Referred Pain from visceral sources Visceral tissues have few pain fibers. Hence, highly localized organ damage causes little pain; however, widespread damage can cause severe pain. Common causes of visceral pain ischemia. chemical irritation. spasm of a hollow viscus. over-distension of a hollow viscus. Often, pain from internal organs is perceived to originate from a distant area of skin. Mechanism: the intermingling of second- order neurons in the dorsal horn of the spinal cord from the skin and viscera, as These are pain fibers Figure 49-5 shown.  Referred Pain Localized to dermatome of embryological origin. Heart localized to the neck, left shoulder, and arm. Stomach localized above the umbilicus. Colon localized below the umbilicus. Understanding referred pain can lead to astute diagnoses that might otherwise be missed. Figure 49-6 Referred Pain (cont.)  Some clinical abnormalities of pain and other somatic sensations Hyperalgesia: altered perception of pain such that stimuli which would normally induce a trivial discomfort causes significant pain. Often caused by damage to nociceptors or peripheral nerves. Tic Douloureux (painful tic): (aka, trigeminal neuralgia) disorder of trigeminal nerve (5th CN) can cause paroxysmal (sudden onset) facial pain. Can be triggered by touch or cold. Late onset: 60-70’s. Level of injury Brown-Sequard syndrome: Ipsilateral symptoms: loss of motor function (i.e. hemiparaplegia), vibration sense, fine touch proprioception (position sense), two-point Dark area shows injury discrimination, and weakness. Contralateral symptoms: loss of pain, temperature sensation, and crude touch. Hemiparaplegia: paralysis of one side of the body  Headache Pain Brain tissue itself is insensitive to pain. Pain sensitive structures include membranes that cover brain and blood vessels: dura. blood vessels of the dura. venous sinuses. middle meningeal artery. Origin of Headache Pain Figure 49-9  Intracranial Headache Meningitis inflammation of meninges cause severe headache. Migraine results from abnormal vascular phenomenon. vasospasm followed by prolonged vasodilation. Vasodilation stretches coverings of blood vessels. Hangover irritation of meninges by alcohol breakdown products and additives.  Relation between migraine and stroke "The results of this meta-analysis indicate that people with migraine are at an increased risk of ischemic stroke. This Meta-analysis: a systematic method of evaluating statistical increased risk is only apparent in those who have migraine with data based on results of several aura and not in those with migraine without aura, the relative risk independent studies of the same being double. In addition, the results suggest an approximately problem. twofold higher risk among women compared with men. Factors Aura: a perceptual disturbance that further increased the risk of ischaemic stroke were age less that occurs in a small % of than 45 years, smoking, and use of oral contraceptives." BMJ. migraine headache victims. 2009; 339: b3914. - precedes or occurs along with the headache. Migraine is associated with increased ischemic stroke risk. These findings underscore the importance of identifying high-risk - often manifests as strange light, unpleasant smell, or migraineurs with other modifiable stroke risk factors. Am J Med. confusing thoughts. 2010, 123(7): 612-24 Migraine with aura in mid-life was associated with late-life prevalence of cerebellar infarcts on MRI. This association was statistically significant only for women. This is consistent with the hypothesis that MA in mid-life is associated with late-life vascular disease that appears to be specific for the cerebellum and in women. JAMA. 2009; 301(24): 25563-70.  Extracranial Headache Muscular spasm, tension headache emotional tension may cause tension of muscles attached to neck and scalp which causes irritation of scalp coverings. Sinus headache irritation of nasal structures. Eye strain excessive contraction of the ciliary muscle in an attempt to focus, contraction of facial muscles. Substance P and Capsaicin Thought to mediate lower back pain, arthritis, fibromyalgia. Over-the-counter creams containing capsaicin (made from chili peppers) can deplete Substance P (by causing its release) from local nerve endings and hence relieve pain. Capsaicin selectively binds to a protein called TRPVI (transient receptor potential cation channel subfamily, member 1) or simply capsaicin receptor, that resides on membranes of pain and heat sensing neurons. The capsaicin receptor is a heat-activated calcium channel, which normally opens between 37 and 45°C; hence, when capsaicin binds to its receptor, a sensation of heat is felt. Prolonged activation of neurons by capsaicin depletes presynaptic substance P, one of the body's neurotransmitters for pain and heat. Birds are not affected by capsaicin… mix with bird https://www.reuters.com/business/healthcare-pharmaceuticals/julius-pat apoutian-win-2021-nobel-prize-medicine-2021-10-04/ Dr. Julius’s lab knew that the receptor they had identified — TRPV1, a channel on the surface of cells activated by capsaicin — had to have evolved primarily for a more common stimulus, beyond the rare instances when someone might encounter hot peppers. That other stimulus turned out to be heat  UNIT 10 Chapter 50: The Eye: I. Optics of Vision Slides by Thomas H. Adair, PhD Copyright © 2021 by Saunders, an imprint of Elsevier Inc. Physiological Anatomy of the Eye White outer layer. Continuous with Suspensory fibers that cornea connect ciliary muscle at front. with lens Transparent, jellylike tissue. Contains photosensitive cells. 2/3 of refractive power Visual acuity is of eye. Resculptured in highest. Cones LASEKS/LASIKS surgery only. Optic disc Aka, Optic nerve head or blind spot. Exit point for axons. Entry point for retinal blood vessels. Nasal to fovea. Free flowing, watery fluid. Fills anterior and posterior CN II. Contains retinal chambers ganglion cell axons and Needed for glial cells. About 1.5 Vascular layer between accommodatio million axons. retina and sclera. Feeds n. outer layers of retina, ciliary body, and iris.  Refractive Index Speed of light in air 300,000 km/sec. Light speed decreases when it passes through a transparent substance. The refractive index is the ratio of speed in air to speed in the substance. For example, if speed in a substance = 200,000 km/sec, R.I. = 300,000/200,000 = 1.5. Light rays bend when passing through an angulated interface with a different refractive index. The degree of refraction increases as the difference in R.I. increases and the degree of angulation increases. Polycarbonate RI: 1.58 Structures of the eye have different R.I. and cause light rays to bend. These light rays are eventually focused on the Figure 50-1 retina. Refractive Principles of a Lens Convex lens focuses light rays Concave lens diverges light rays. TMP14, Figure 50-2 TMP14, Figure 50-3 Note that a point source of light has a longer focal length compared to light from a distant source; this is why an object comes into focus as it moves closer to the eye in a person with myopia (nearsightedness, long eyeball).  Refractive Power of the eye - Diopter 2/3 of the refractive power of the eye resides in the anterior 1000/17 = 59 diopters surface of the cornea. This refraction is virtually eliminated 17 mm when swimming underwater since water has a refractive index close to that of the cornea; hence, you get a blurry image underwater. Lens has less refractive power, TMP14, Figure 50-8 but it’s adjustable. – a diopter is a measure of the power of a lens. – 1 diopter is the ability to focus parallel light rays at 1 meter. – the retina is about 17 mm behind refractive center of eye. – hence, the eye has a total TMP14, Figure 50-9 refractive power of 59  Accommodati on Refractive power of lens is 20 diopters. Refractive power can be increased to 34 diopters by making lens thicker; this is called accommodation. Accommodation is necessary to focus image on retina. An untethered lens is almost spherical in shape. Lens is held in place by suspensory ligaments (zonule fibers) which under normal resting conditions causes the lens to be almost flat. TMP14, Figure 50-8 Contraction of ciliary muscle decreases tension in the suspensory ligaments, allowing the lens to become more spherical (thicker); this increases the refractive power of lens. Under control of parasympathetic nervous system. TMP14, Figure 50-10 Presbyopia: Also called age-related farsightedness, it’s the inability to accommodate. With age, the lens gets harder and less flexible because of decreased levels of Power of accommodation α-crystallin. decreases with age: Child, 14 diopters (34-20) 50 years old, 2 diopters 70 years old, 0 diopters  Errors of Refraction Normal vision corrected with convex lens Far sightedness corrected with concave lens Near sightedness Guyton, Figure 50-12 Astigmatism: unequal focusing of light rays due to an oblong shape of the cornea. Hyperopia and Myopia ciliary muscle relaxed HYPEROPIA (farsightness) caused by a short eyeball or sometimes a weak lens. contraction of ciliary muscle increases strength of lens (i.e., reduces focal distance). “farsightedness” So, a farsighted person can focus distant objects on retina because of accommodation. If there is sufficient accommodation left, a Ciliary muscle relaxed farsighted person can also focus close objects on Ciliary muscle contracted retina. MYOPIA (nearsightness) caused by a long eyeball or sometimes too much ciliary muscle relaxed refractive power in lens system. Genetic and environmental factors contribute to myopia – too much close work can promote myopia. No mechanism to focus distant objects on retina (contraction of ciliary muscle would make distant “nearsightedness” objects even more out of focus). Objects come into focus as they move closer to As an object moves toward the eye. eye, the rate of parasympathetic stimulation increases, causing the ciliary muscle to contract. What happens to the lens?  Why does squinting help you see better? When we squint it creates the same effect as looking through a pinhole. Basically, only a small amount of focused central light rays are allowed into the eye. This prevents the unfocused light rays in the periphery from reaching the retina. The result is better vision. Photographers understand this as “depth of field”.  Cataracts leading cause of blindness Cataracts worldwide – cloudy or opaque area of the lens caused by coagulation of lens proteins – Accounts for about half the cases of blindness in the world. – UV solar radiation is major factor in production of cataracts Surgical implantation of plastic lens can usually restore vision. ~6 million per year.  Visual Acuity 20/20 – ability to see letters of a given size at 20 feet (normal vision) 20/40 – what a normal person can see at 40 feet, this person must be at 20 feet to see. 20/200 – what a normal person can see at 200 feet, this person must be at 20 feet to see. 20/15 – Means what? Snellen chart  Fluid System of the Eye Intraocular fluid keeps the eyeball round and distended. 2 fluid chambers. aqueous humor, in front of lens. (freely flowing fluid). vitreous humor, behind lens (gelatinous mass with little fluid flow). Produced by ciliary body at rate of 2-3 microliters/min. (~3-4 mL/day) Flows through pupil into anterior chamber; then between cornea and iris, through meshwork of trabeculae to enter the canal of Schlemm, which empties into extraocular veins. TMP14, Figure 50-19  Intraocular Pressure Normally 15 mm Hg (range: 2-20 mm Hg). Level of pressure is determined by resistance to outflow of aqueous humor in canal of Schlemm. Hall, Figure 50- 21 Rate of production of aqueous humor is constant under normal conditions (can be increased in systemic hypertension). Long-term hypertension is a risk factor for glaucoma. Increased pressure can cause blindness due to compression of axons of optic nerve as well as blood vessels.  Glaucoma 2nd leading cause of blindness worldwide (after cataracts) Usually caused by high intraocular pressure (IOP). Increased IOP compresses blood vessels and axons of optic nerve at optic disc; this leads to poor nutrition of nerve fibers. Two main types of glaucoma Open angle and closed angle (angle refers to area between iris and cornea). Open angle glaucoma (also called Chronic glaucoma) 90% of cases in U.S. Insidious – no pain initially reduced flow through trabecular meshwork (tissue debris, WBC, deposition of fibrous material, etc). Types of Glaucoma Eye Drops Closed angle glaucoma Prostaglandin analogs - increase outflow of fluid 10% of cases in U.S. – sudden closure of from eye. iridocorneal angle with sudden ocular pain. A Beta blockers – decrease production of intraocular fluid. medical emergency. Alpha agonists - decrease fluid production and Treatment: Laser peripheral iridotomy (LPI), increase drainage. where an opening in the iris is made using a Carbonic anhydrase inhibitors (CAIs) – decrease  UNIT 10 Chapter 51: The Eye: II. Receptor and Neural Function of the Retina Slides by Thomas H. Adair, PhD Copyright © 2021 by Saunders, an imprint of Elsevier Inc.  Retina Light sensitive portion of eye. Contains cones for color vision. Contains rods for night vision. Contains neural architecture. Light must pass through neural elements to activate light- sensitive rods and cones. But this is not so bad since neural elements are virtually transparent in vivo. Each retina has 100 million rods; 3 million cones; and 1.6 million ganglion cells. TMP14, Figure 51-1  The Fovea It’s a small area at the center of the retina, ~1 mm2. The center of the fovea, called “central fovea” or “fovea centralis,” contains only cones. these cones have a special structure. Aid in detecting detail. In the central fovea, neuronal cells and blood vessels are displaced to each side so light can strike cones with less obstruction. This is the area of greatest visual acuity. At central fovea: no rods, and the ratio of cones to bipolar cells is 1:1; this explains the high degree of visual acuity in the central retina. Figure 51-2 The Fovea Figure 51-2 Distribution of rods and cones Structure of Rods and Cones Pigment layer Guyton, Figure 51-4 Guyton, Figure 51-3  Rods and Cones RODS CONES high sensitivity; specialized for night vision lower sensitivity; specialized for day vision (scotopic vision) (photopic vision) more photopigment less photopigment high amplification; single photon detection less amplification saturate in daylight saturate only with intense light slow response, long integration time fast response, short integration time more sensitive to scattered light more sensitive to direct axial rays low acuity; highly convergent retinal pathways, high acuity; less convergent retinal pathways, not present in central fovea concentrated in the central fovea Achromatic; one type of rod pigment Trichromatic; three types of cones, each with a (rhodopsin) different pigment (photopsin) that is sensitive to a different part of visible spectrum More common in the periphery More common in the fovea and macula  Pigment Layer of Retina Contains black pigment called melanin. Prevents light reflection in globe of eye. Without pigment, light would scatter diffusely; normal contrast between dark and light would be diminished. Albinos lack pigment layer poor visual acuity because of scattering of light. Even with corrective lenses, vision is rarely better than 20/200. Pigment epithelium/choroid TMP14, Figure 51-1 contains high levels of vitamin A (needed for phototransduction). Visual Phototransduction Conversion of light into electrical signals Rhodopsin resides ROD in disk membrane Rhodopsi Occurs in rods, cones and photosensitive of outer segment of n rod and encloses ganglion cells. light sensitive 11- The pigment protein in rods is called cis retinal rhodopsin; molecule. The pigment protein in cones is called photopsin, a close analog of rhodopsin Absorption of a (there are 3 types of photopsin: types I photon of light by retinal leads to a (red), II (green), and III) (blue). change in The pigment portion of photosensitive configuration from retinal ganglion cells is called 11-cis to all-trans 11-cis retinal melanopsin. retinal. The retinal The transduction mechanism is similar for light then breaks away The rods, cones, and probably light sensitive all-trans retinal is then reduced from rhodopsin, ganglion cells. retinol, which then to all-trans causing rhodopsin to be activated. travels back to the retinal pigment 11-cis retinal epithelium layer to be “recharged” to The activated become 11-cis retinal. rhodopsin (aka, The 11-cis retinal travels back to the Metarhodopsin II) rod where it is conjugated to an opsin then begins the 2nd All-trans retinal to form new rhodopsin or a new messenger cascade which leads to photopsin.  Vitamin A1 is required for Phototransduction Vitamin A1 (aka, all-trans retinal) is converted into 11-cis retinal within the retinal pigment epithelium. Food source: two types found in diet. Preformed vitamin A: animal products such as meat, fish, poultry and dairy foods. Pro-vitamin A: plant-based foods such as fruits and vegetables. The most common type of pro- vitamin A is beta-carotene. Pro-vitamin A is a Vitamin A deficiency precursor of vitamin A. the leading cause of preventable childhood blindness worldwide in developing countries Prolonged and severe vitamin A deficiency can produce total and irreversible blindness. TMP14, Figure 51-5 ~250,000–500,000 children become blind each year (with the highest prevalence in Southeast Asia and Night Africa). (nyctalopia): Lack of vitamin blindness A1 causes a decrease in retinal, which results in decreased production of rhodopsin; and a lower sensitivity Night of retina blindness can to light. occur in patients with GI absorption problems, e.g., celiac disease and cholestasis. Why? Br J Ophthalmol. 2006 Aug; 90(8): 955–956. http://medical-dictionary.thefreedictionary.com/vitamin+A+deficiency  Rod Receptor Potential Normally about -40 mV (in dark). Normally, the outer segment of the rod is Na+ Ca++ permeable to Na+ and Ca++ ions. In the dark, an inward current (the dark Dark current) carried by Na+ and Ca + + ions flows current into an outer segment of the rod. An outward current carried by K+ ions occurs in the inner segment of the rod. When rhodopsin decomposes, it causes hyperpolarization of the rod by decreasing the Na+ and Ca++ permeability of the outer segment. TMP14, Figure 51-6 Greater amounts of light produce greater electronegativity. -40 mV -70 mV So, photoreceptor cells depolarize in scotopic conditions (low light or Ca++ no light) and hyperpolarize in Ca++ photopic conditions (well-lit conditions). Phototransduction – Closure of cGMP-gated Na+ and Ca++ channels with subsequent hyperpolarization (1) Light activated rhodopsin (metarhodopsin II) activates transducin. (2) Transducin activates cGMP phospho- diesterase, which destroys cGMP. (3) cGMP levels decrease, (4) causing sodium channels to 1 2 close. 4 (5) Closure of sodium channels causes photoreceptors to 3 hyperpolarize Metarhodopsin II is deactivated 5. -40 mV →-70 mV Na+, Ca++ rapidly after activating transducin channel TMP14, Figure 51-7 by rhodopsin kinase and arrestin.  Duration and Sensitivity of Receptor Potential Rods: a single pulse of light activates receptor potential for more than 1 s. Cones: occurs 4 X faster. Receptor potential is proportional to the logarithm of light intensity. Information within the neural elements of the retina is conveyed by electrotonic potentials, not action potentials. very important for discrimination of light intensity.  Color Vision Color vision results from activation of cones. The pigment protein in cones is called photopsin, a close analog of rhodopsin (there are 3 types of photopsin: types I (red), II (green), and III) (blue). The retinal portion of the photopsins is the same as in rods. Each cone is receptive to a particular wavelength of light. Figure 51-8  Color Blindness Lack of a particular type of cone. Genetic disorder mostly passed along on X chromosome. Hence, occurs almost exclusively in males. Blue color blindness affects both men and women equally, because it is carried on a non-sex chromosome. Most color blindness results from lack of red or green cones. lack of a red cone, protanope lack of a green cone, deuteranope Lack of a blue cone, tritanopia What happens in hereditary color deficiency? Red or green cone peak sensitivity is shifted. Red or green cones absent. Normal cone sensitivity curves (TRICHROMAT) 533 437 nm 564 nm nm B G R Deuteranomaly (green shifted toward red) 437 nm 564 nm 5% of Males B G R  Deutan Dichromat (no green cones; only red and blue) 437 nm 564 nm 1% of Males (there is no green B R curve) Deuteranope Vision Normal Color Deuteranope, shades of orange, no yellow or green  Protanomalous (red shifted toward green) 533 nm 1% of 437 nm Males B G R 150  Protan Dichromat (no red cones; only green and blue) 1% of 533 nm Males 437 nm (there is no red curve) B G  Protanomaly Normal Protanomaly  Protanope Vision Normal Vision Protanope, red-green colors are difficult to distinguish  Neural Organization of Retina Direction of light Figure 51-12  Signal Transmission in the Retina Neural elements in retina use electrotonic potentials (aka, graded potentials) to move current along their membranes instead of action potentials (exceptions include ganglion cells and some of the amacrine cells). The electrotonic potentials allow graded conduction of signal strength proportional to light intensity. Ganglion cells have action potentials. send signals to the brain via the optic nerve (CN 2). spontaneously active with continuous action potentials. visual signals are superimposed on this background. many excited by changes in light intensity. Figure 51-12 Respond to contrast borders; this is how the pattern of the scene is transmitted to the brain.  Lateral Inhibition Processing the visual image begins in Enhances visual contrast. the retina. One example is lateral inhibition. Horizontal cells provide inhibitory feedback to rods and cones and bipolar cells. Output of horizontal cells is always inhibitory. Prevents lateral spread of light excitation on retina. Contrast is enhanced with excitatory center and inhibitory surround. TMP14, Figure 51-12 TMP14, Figure 51-13 Lateral Inhibition (cont.) APs from ganglion cell 1. Area excited by spot of light. 2. Area adjacent to Figure 51-14 excited spot. Lateral inhibition, the function of horizontal cells Figure 51-15  The Optic Disc (also called the optic nerve head) What is it? point where ganglion cell axons (~1 million) exit the eye to form the optic nerve (2nd cranial nerve). entry point for retinal blood vessels creates a blind spot since there are no rods or cones. located 3-4 mm to the nasal side of the fovea. size: 1.76mm (horizontally) edematous optic disc x 1.92mm vertically Has a central depression Aka, papilledema called the optic cup Function of Amacrine Cells About 30 different types. Their primary targets are ganglion cells Some are involved in the direct pathway from rods to bipolar cells to amacrine cells to ganglion cells. A few have action potentials Some amacrine cells respond strongly to the onset of the visual signal, some to the extinguishment of the signal. Some respond to movement of a light signal across the retina. Amacrine cells are a type of interneuron that aid in the beginning of visual signal analysis. Figure 51-12 Most (but not all) amacrine cells release inhibitory transmitters, GABA or glycine. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3 652807/  Ganglion Cells More than 20 different types Different types respond to the following: Specific directions of motion or orientation Fine detail Increases or decreases in light Two classes of ganglion cells: P and M Particular colors cells P cells (parvocellular cells): Project to parvocellular layers of lateral geniculate nucleus (LGN) of thalamus Small receptive fields, slow impulse conduction, sensitive to color and fine details, relatively insensitive to low- M cells (magnocellular cells): Figure 50-12 contrast signals Project to magnocellular layers of lateral geniculate nucleus of thalamus Larger receptive fields Fast impulse conduction The lateral geniculate nucleus has More sensitive to low contrast B&W multiple parvocellular and stimuli magnocellular layers.  UNIT 10 Chapter 52: The Eye: III. Central Neurophysiology of Vision Slides by Thomas H. Adair, PhD Copyright © 2021 by Saunders, an imprint of Elsevier Inc.  Visual Pathways to the Cortex Optic nerve - axons of ganglion cells of the retina. (of thalamus) Optic chiasm. all fibers from nasal halves of the retina cross to the opposite sides and join fibers from the opposite temporal retina to form optic tracks. Synapse in the dorsal lateral geniculate nucleus (LGN) of the thalamus. From LGN to the primary visual cortex by way of the optic radiation. Two principal functions of LGN. Relay information to the primary visual cortex via optic radiation. “Gate control” of information to the Figure 52-1 primary visual cortex. Lateral Geniculate Nucleus: Relay Function Half of the fibers in each optic tract are derived from one eye, and half from the other eye. Signals from the two eyes are kept apart in the LGN. Layers 2, 3, and 5 receive input from ipsilateral eye Layers 1, 4, and 6 receive input from contralateral eye Kandel, Schwartz and Jessell 4th edition 2000, McGraw Hill fig 26-4  Lateral Geniculate Nucleus: Gate Function LGN controls (gates) how much signal passes to cortex. LGN receives gating control signals from corticofugal fibers originating in the primary visual cortex (not shown) Reticular areas of the midbrain (not shown) Both inputs are inhibitory and can turn off signal transmission in select areas of LGN. So, both inhibitory inputs control the visual input that is allowed to pass to cortex. Also, signals are provided to: A. Control the vergence of the eyes so they converge at the object of interest. B. Control the focus of the eyes based on calculated distance to object of interest. Kandel, Schwartz and Jessell Information is also provided 4th edition 2000, McGraw Hill describing the velocity of major fig 26-4 elements in central field of vision, and which way the organism (person) is moving relative to  Primary Visual Cortex Primary visual cortex lies in calcarine fissure. Distribution from eye is shown. Note the large area of representation of the macula (which includes the fovea). Fovea has 100x more representation in cortex compared to peripheral portions of retina. Secondary visual areas are visual association areas, where the visual image is dissected and analyzed. Figure 52-2 Analysis of the Visual Image the visual signal in the primary visual cortex is concerned mainly with contrasts in the visual scene. the greater the sharpness of the contrast, the greater the degree of stimulation. also detects the direction of orientation of each line and border. for each orientation of a line, a specific neuronal cell is stimulated. Visual Perception is a Creative Process how the brain perceives a visual image is not understood well. visual perception is thought to be mediated by three parallel pathways that process information on motion, depth and form, and color.  Autonomic innervation of eye Parasympathetic preganglionic fibers arise from Edinger-Westphal Ciliary nerve nucleus and synapse with postganglionic fibers in ciliary ganglion as shown. The postganglionic fibers send action potentials through ciliary nerves to eyeball to control: 1. ciliary muscle (lens focusing) 2. Sphincter of iris (constricts pupil) Sympathetic preganglionic fibers originate in intermediolateral horn of 1st thoracic segment of the cord and synapse with postganglionic fibers in the superior cervical Figure 51-11 ganglion as shown. The postganglionic fibers innervate radial fibers of the iris (which open the pupil), plus several extraocular  Control of Accommodation Recall that accommodation is the mechanism that focuses the lens system. The lens system focused on a distant object can refocus on a close object in less than 1 s. Parasympathetic control mechanism is poorly understood Chromatic aberration: red light rays focus posteriorly compared to blue light rays. Eye can tell which is in better focus and relay information to accommodation mechanism. (seems unlikely since color-blind people can still focus) Convergence: neural signal for convergence cause simultaneous signal to strengthen lens. Fovea lies in the depression of the retina. Differences between foveal image and image of surrounding retina may also give clues about which way lens should respond. Oscillation of the degree of accommodation occurs all the time (2x per second). An Figure 52-11 image becomes better focused when lens thickness is changing in the right direction…  Control of Pupillary Diameter Pupils constrict when the amount of light entering the eyes increases. Functions to help eyes adapt to Pupillary light reflex extremely rapid changes in light pupil conditions. Parasympathetic nerves excite pupillary sphincter muscle, decreasing pupillary aperture (miosis). Sympathetic nerves excite radial fibers of the iris, causing pupillary dilation (mydriasis). Pupillary light reflex: Figure 52-11 Light on the retina causes a few impulses to pass from optic nerves to pretectal nuclei.  Atropine dilates the pupil (mydriasis) and inhibits accommodation …by blocking parasympathetic effects; it is a competitive antagonist for muscarinic acetylcholine receptors, (increased heart rate, dry mouth, decreased sweating/lacrimation, blurry vision, vasodilation, confusion, hallucinations). Mnemonic: "hot as a hare, blind as a bat, dry as a bone, red as a beet, and mad as a hatter". Atropine is extracted from the plant, nightshade (Atropa belladonna). Belladonna (in Italian: bella=beautiful; donna=woman) Used by Egyptians (Cleopatra), and throughout Europe (late 19th, early 20th century) to enhance beauty. Atropine Mnemonic, i.e., anticholinergic effects Blind as a bat: Mydriasis -- photophobia, blurred vision Bloated as a toad: Constipation Dry as a bone: Anhidrosis, dry mouth, or dry skin Full as a flask: Urinary retention – relaxes bladder sphincter Hot as a hare: Fever or hyperthermia - suppresses sweating Red as a beet: flushing – suppresses sweating The heart runs alone: Tachycardia Binocular and stereoscopic vision Binocular – to see (an object) with both eyes simultaneously. Stereoscopic – to see things as 3-D. We have a fixed visual angle of 104⁰, and our eyes are close together. Hence, visual fields overlap as shown, which allows accurate judgment of distance. Slightly different images from each eye are sent to brain, where impulses are fused to make single image. This allows 3-D imaging. Predatory animals (hawks, lions) have eyes set in front, and good binocular and stereoscopic vision. Preyed upon animals (rabbits) have eyes on sides of head and a wide visual field. This arrangement is good for detecting movement, but provides poor stereoscopic vision.  Retinitis Pigmentosa Refers to large group of disorders with clinical and genetic heterogeneity. Main risk factor is family history Incidence (1 in 4,000) Characterized by pigment deposition Symptoms Night blindness (rods often go first) Decreased peripheral vision Loss of central vision in advanced cases Treatment No effective treatment Sunglasses to reduce UV  UNIT 10 Chapter 53: The Sense of Hearing Slides by Thomas H. Adair, PhD Copyright © 2021 by Saunders, an imprint of Elsevier Inc.  The Tympanic Membrane and the Ossicular System Tympanic membrane functions to transmit vibrations in the air to the cochlea (inner ear) Amplifies the signal because the area of the tympanic membrane is 17 times larger than the oval window. Tympanic membrane connected to the ossicles: malleus, incus, stapes Figure 53-1 Attenuation of Sound by Muscle Contraction Two muscles attach to the ossicles – Stapedius (stapes) – Tensor tympani (malleus) Stapedius is the smallest skeletal muscle in the body (1 mm long) Attenuation reflex (aka, stapedius reflex, acoustic reflex, auditory reflex): a loud noise initiates reflex contraction, causing the ossicular system to develop rigidity. Both muscles are involved. Attenuates vibration going to the cochlea. Can reduce sound transmission by 30-40 decibels. Serves to protect the cochlea and dampens low-frequency sounds, i.e., your own voice (~1000 Hz) or the voice of others. (Humming when you don't want to hear someone else works through the stapedius reflex; this can be a 20- decibel reduction in sound transmission to the cochlea)  Cochlea Encased in bone Hearing loss: conduction and/or neurological System of three coiled tubes separated by membranes into the scala tympani, scala media, scala vestibuli Sound waves cause back and forth movement of the tympanic membrane which moves the stapes back and forth. This causes displacement of fluid in Figure 53-3 the cochlea and induces vibration in the basilar membrane. Organ of Corti lies on surface of basilar membrane; contains hair cells which are The cochlea electromechanically is completely developed sensitive. by the middle of gestation, and has reached adult size: no further gain in size or change in shape is expected after birth Figure 53-1  Organ of Corti Receptor organ that generates nerve impulses. Contains rows of hair cells that have stereocilia. Hair cells are the receptor organs that generate APs in response to sound vibrations. The tectorial membrane lies above the stereocilia of the Figure 53-7 hair cells. Movement of the basilar membrane causes the stereocilia of the hair Nerve Impulse Origination Stereocilia: The hair cells depolarize when bent in one direction; they hyperpolarize when bent in opposite direction. – this is what begins neural transduction of auditory signal. ~90% of auditory signals are Inner hair cells transmitted by inner hair cells. – 3-4 X more outer hair cells than inner hair cells. – outer hair cells may control the sensitivity of inner hair cells for different sound pitches. Figure 53-7 Inner and outer hair cells outer hair cells may control the sensitivity of the inner hair cells for different sound pitches. auditory signals are transmitted by the inner hair cells. Kandel, Schwartz and Jessell 4th edition 2000, McGraw Hill fig 30-5 Outer hair cells adjust sensitivity there are nerve fibers running from the brain stem to the vicinity of the outer hair cells, may function to adjust sensitivity by acting on these cells. Kandel, Schwartz and Jessell 4th edition 2000, McGraw Hill fig 30-10 Structural components of Cochlea Basilar membrane contains ~30,000 fibers which project from the bony center of the cochlea, the modiolus. Fibers are stiff reed-like structures fixed to the modiolus and embedded in the loose basilar membrane. Because they are stiff and free at one end they Short, stiff, can vibrate like a musical Long, limber, high frequency Low frequency reed. the length of the fibers Figure 53-4 increases, and the diameter of the fibers decreases from the base The round window serves to decompress at the oval window to the acoustic energy that enters the cochlea via helicotrema; overall stapes movement against the oval window. stiffness decreases 100 X,  Determination of Sound Frequency and Amplitude Place principle determines the frequency of sound perceived. – different frequencies of sound will cause the basilar membrane to oscillate at different positions. – position along the basilar membrane where hair cells are being stimulated determines the pitch of the sound being perceived. Amplitude is determined by how much the basilar Figure 53-5 membrane is displaced.  Decibel Unit of Sound Unit of sound Sound intensity is expressed in terms of the logarithm of their actual intensity because of the wide range in sound intensity. A 10-fold increase in sound energy is 1 bel 0.1 bel is a decibel 1-decibel is an increase in sound energy of 1.26 times Ears can barely distinguish a 1-decibel change in sound intensity. Decibel values for various sounds Does the attenuation reflex protect against a shotgun blast?  Noise-induced hearing loss Pathophysiology Most common cause of acquired – 1st, decreased stiffness of hearing loss stereocilia of outer hair Approximate Decibel Level Examples cells. 0 dB the quietest sound you can hear. – 2nd, loss of stereocilia. 30 dB whisper, quiet library. – 3rd, loss of entire hair 60 dB normal conversation, sewing machine, typewriter. cells can occur (by lawnmower, shop tools, truck traffic; 8 hours 90 dB per day is the maximum exposure (protects phagocytosis). 90% of people). chainsaw, pneumatic drill, snowmobile; 2 100 dB hours per day is the maximum exposure Causes: cochlear without protection. inflammatory response; 115 dB sandblasting, loud rock concert, auto horn; 15 minutes per day is the maximum exposure generation of reactive without protection. oxygen species; metabolic gun muzzle blast, jet