5.1 Sensory Receptors and Signal Transduction
Sensory receptors are specialized cells or neurons that are dedicated to the task of transducing stimuli into nerve action potentials.
Classification of Receptors
Sensory receptors are classified as mechanoreceptors, chemoreceptors, photoreceptors, or thermoreceptors, depending on the type of energy to which they respond.
They can also be categorized according to the location from which the stimulus induces a response:
– Exteroceptors respond to stimuli originating outside the body.
– Interoceptors respond to stimuli from within the body (e.g., visceroceptors, equilibrium receptors of the inner ear, and proprioceptors that sense the positions and movement of muscles, bones, and joints).
Morphology of Receptors
Sensory receptors may be one of the following:
– Free nerve endings
– Nerve endings associated with connective tissue capsules
– Sensory endings synaptically linked to receptor cells. When these receptor cells are depolarized, synaptic vesicles containing neurotransmitter are released onto sensory afferent nerve endings.
The variety of skin receptors are shown in Fig. 5.1.
Fig. 5.1 Skin receptors.
The various sensory receptors in hair-bearing skin and in hairless skin are shown. Nociceptors, and receptors for heat and cold are free nerve endings. Pain receptors, or nociceptors, constitute about half of all receptors.
From Thieme Atlas of Anatomy, Head and Neuroanatomy, © Thieme 2007, Illustration by Markus Voll.
Electrophysiology of Receptors and Signal Transduction
Application of a stimulus to a sensory nerve ending produces an electronic potential across the cell membrane known as a generator potential. In receptor cells, the electronic potential resulting from a stimulus is termed a receptor potential.
Receptor and generator potentials are generally depolarizations caused by ion influx into the nerve ending or receptor cell.
Note: An important exception is light acting on the photoreceptors in the retina, leading to a decreased influx of ions and hyperpolarization.
Electronic potentials are graded; that is, as the intensity of the applied stimulus is increased, the magnitude of the potential change increases concomitantly.
– In the case of generator potentials, when threshold is reached, an action potential is propagated along the afferent nerve. The trigger point for the action potential is the first node of Ranvier.
– In the case of receptor potentials, the quantity of synaptic transmitter released by receptor cells is proportional to the magnitude of the receptor potential. If threshold is reached, an action potential is propagated along the afferent nerve.
Generator and receptor potentials can exhibit temporal summation in response to repetitive stimuli.
Coding of Stimulus Intensity
Information about the intensity of an applied stimulus detected by a sensory receptor is carried to the central nervous system (CNS) by the afferent nerve fiber as a frequency code. The magnitude of the stimulus is coded by the firing frequency of the nerve fiber (spikes per second). This, in turn, determines the frequency of release of neurotransmitter at the synapse (Fig. 5.2).
The number of afferent fibers recruited by the applied stimulus is another indicator of stimulus intensity.
Adaptation is the term used to describe the steadily reduced rate of firing of some afferent nerves associated with sensory receptors that occurs when a constant stimulus is applied to the sensory receptor for a prolonged period. The psychological perception of the intensity of the stimulus is concurrently reduced.
Fig. 5.2 Stimulus processing and information coding.
The original stimulus is coded by frequency for transmission along nerve fibers and decoded by bursts of neurotransmitters from presynaptic nerve terminals. Such neurotransmitters initiate action potentials (APs) in the next neuron that imitates the original stimulus.
Slowly adapting (tonic) receptors
– The afferent nerves associated with these receptors will continue to fire action potentials at the same rate when a constant stimulus is applied.
– Slowly adapting receptors signal the magnitude of a stimulus.
Rapidly adapting (phasic) receptors
– The afferent nerves associated with these receptors will rapidly reduce their rate of firing of action potentials when a constant stimulus is applied.
– Rapidly adapting receptors signal onset and offset of a stimulus.
The adaptation rates of somatosensory receptors are listed in Table 5.1.
5.2 Somatosensory System
Somatosensory sensations are grouped into two broad divisions:
– The discriminative touch system is responsible for touch, pressure, and vibration sensibility. The mechanoreceptors for this system are included in Table 5.1
– The pain and temperature system
Sensory information from each of these systems is conveyed to the cortex by different somatosensory tracts.
Sensory afferent nerves travel to the spinal cord in the posterior (dorsal) roots.
Dorsal Column System
This system conveys discriminative touch information in the spinal cord to higher centers. It also carries information concerning position sense from proprioceptors at skeletal joints.
– The sensory afferent nerves of this system are myelinated Aβ fibers.
Course of the dorsal column system
– Primary afferent neurons (first-order neurons) ascend in the spinal cord in the dorsal (posterior) columns without synapsing. They synapse in the dorsal column nuclei (nucleus gracilis and nucleus cuneatus) of the medulla.
– The second-order neurons decussate (cross the midline) and pass to the relay nuclei of the thalamus (ventral posterolateral [VPL]) via the medial lemniscus. The information is arranged topographically in the thalamus.
– Thalamocortical projections (third-order neurons) carry the information to the postcentral gyrus of the parietal lobe.
Course of sensation from the head and face
– Sensation arising from tactile stimulation of the face and head is carried by the trigeminal nerve to the principal sensory nucleus of the trigeminal in the pons.
– Second-order fibers decussate and ascend via the trigeminothalamic tract to the ventral posteromedial (VPM) nucleus of the thalamus.
– Thalamocortical projections relay the information to the face area of the postcentral gyrus of the parietal lobe.
Two-point discrimination is the ability to discriminate one mechanical stimulus touching the skin from two stimuli. Sensitivity varies from one region of the body surface to another. The thresholds for discriminating two stimuli are lower on the tongue, fingers, and lips than they are at other locations, such as the back. This is correlated with the greater density of sensory receptors and, hence, their smaller receptive fields in these sensitive areas.
The strip of skin innervated by the posterior (dorsal) root of a single spinal segment is known as a dermatome. A dermatomal map is important for localizing injuries to peripheral sensory nerves.
This system conveys pain and temperature information in the spinal cord to higher centers.
– The spinothalamic pathway of the anterolateral system is responsible for the discriminative aspects of pain perception, such as localization and magnitude estimation.
– The spinoreticular pathway of the anterolateral system is responsible for the arousal, autonomic, and emotional responses to pain.
– The sensory afferents of this system are myelinated Aδ and unmyelinated C fibers.
Course of the anterolateral system
– Primary afferent neurons (first-order neurons) enter into the dorsal horn of the spinal cord gray matter and synapse with interneurons and projection neurons of the substantia gelatinosa.
– Second-order neurons decussate in the spinal cord and ascend in the anterolateral tract to terminate in the VPL nucleus of the thalamus or in the brainstem reticular formation.
– Third-order neurons project from the VPL nucleus to the somatosensory cortex of the parietal lobe. The reticular formation projects diffusely to the forebrain and brainstem areas, which are believed to be involved in the affective responses to pain (amygdala and anterior cingulate gyrus).
Course of pain sensations from the head and face
– Pain originating from the head and face is carried first by pain afferent fibers in the trigeminal nerve that synapse in the descending (spinal) nucleus of the trigeminal nerve.
– Second-order fibers decussate and ascend to the thalamus and reticular formation.
Table 5.2 summarizes the features of dorsal column and anterolateral systems. Their course is illustrated in Fig. 5.3.
Fig. 5.3 Somatosensory tracts.
(VPLN, ventral posterolateral nucleus; VPMN, ventral posteromedial nucleus)
Primary Sensory Cortex
The primary sensory cortex (S1) is located on the postcentral gyrus of the parietal lobe. The body surface is mapped onto the cortical surface in a strict, somatotopic fashion in the form of a sensory homunculus. The map reflects the density of skin innervation rather than the actual area, with greater cortical area devoted to the index finger and lips than to the back (Figs. 5.4 and 5.5).
Afferent Input to the Primary Sensory Cortex
– Somatic sensory area 2 (S2) adjoins the lower posterior portion of area 1 on the parietal cortex. It receives information from both sides of the body with low synaptic security. It is particularly sensitive to direction of stimulus movement on the body surface.
– The secondary somatosensory area is located on the parietal cortex (areas 5 and 7) directly posterior to the postcentral gyrus. It mediates stereognosis (the ability to determine form via touch) and complex perceptions (e.g., spatial orientation). It forms associations between the somatic, auditory, and visual systems.
Fig. 5.4 Sensory centers of the brain.
The contralateral side of the body is represented on somatic sensory area 1 (S1) of the parietal cortex. S2 receives sensory information from both sides of the body. The cortical areas that process hearing and vision are also shown.
Fig. 5.5 Somatotopic organization of S1.
S1 has somatotopic organization, meaning that each part of the body is represented at a particular cortical area. The size of the cortical area devoted to each part is determined by the density of its sensory receptors.
Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or perception of such damage. It serves a protective function in signaling tissue injury or processes that might damage tissue. The responses to pain may be autonomic, psychological, emotional, or behavioral.
– Morphologically, pain receptors, or nociceptors, are simple free nerve endings in the skin or other tissues.
– They respond specifically to intense mechanical, thermal (hot or cold), or chemical stimulation. Some nociceptors are unimodal, responding to only one energy form. Others are polymodal and are activated by two types of stimulus energy.
Afferent Pain Fibers
– Myelinated Aδ fibers rapidly convey “first” pain, characterized as short, sharp pain that is easily localized. This type of pain usually originates in the skin.
– Unmyelinated C fibers slowly convey “second” pain, or diffuse, aching, burning, or throbbing pain that is poorly localized. This type of pain may originate in skin, muscles, joints, or viscera.
– The main transmitter released by the afferent pain fibers is glutamate. Many fibers also release peptide transmitters, particularly substance P.
Sensitization of Afferent Pain Fibers
Tissue injury or inflammation can lower the threshold for activation of nociceptor afferents. Inflammatory mediators such as bradykinin, prostaglandins, cytokines, and histamine released by leukocytes, platelets, and mast cells, as well as adenosine triphosphate (ATP) and H+ ions released by damaged cells, act on the nociceptor terminals to increase firing rates and lower the threshold for activation.
– Allodynia, painful perception produced by normally innocuous stimuli, is one manifestation of sensitization. An example of this phenomenon is the temporary sensitization of the skin to light touch following sunburn.
– Hyperalgesia refers to the increased intensity of the pain perception resulting from sensitization.
Referred pain occurs because somatic (relating to the body) and visceral (relating to the internal organs) afferent fibers converge onto the same projection neuron of the dorsal horn. Referred pain originates from the viscera but is perceived as if coming from an overlying or nearby somatic structure within the same dermatome (Fig. 5.6).
Local anesthetics (e.g., lidocaine) are drugs that act by blocking the inner gate of the Na+ channel in nerve axons, thus preventing action potential generation and nerve conductance. Smaller diameter unmyelinated nerve fibers are more sensitive to block by local anesthetics than larger diameter myelinated fibers. This results in a definite order in which sensation is blocked: pain (carried in small unmyelinated fibers), followed by sensations of cold, warmth, touch, and deep pressure. Proprioceptive and motor fibers are blocked last.
Non–drug treatment of pain
Intractable or chronic pain may be interrupted surgically at successively higher levels of the neuraxis by anterior cordotomy, medullary tractotomy, thalamotomy, or frontal lobotomy. Spinal cord stimulation, transcutaneous electrical nerve stimulation (TENS), and acupuncture excite larger afferent fibers that may “close the (spinal) gate” for relay of noxious stimuli conducted in smaller afferent fibers (gate control theory of pain). Endogenous opioid peptides (enkephalins, β-endorphins, and dynorphins) may activate opioid receptors that suppress pain transmission at the level of the spinal cord, especially of the spinothalamic tract cells. Release of peptides can be produced by activation of a common descending pathway that originates in the periaqueductal gray matter (PAG) of the midbrain, synapses in the nucleus raphe magnus, descends to the gray matter of the spinal cord, and makes either presynaptic or post-synaptic contact onto interneurons or spinothalamic tract cells.
Fig. 5.6 Mechanism of referred pain.
The convergence of somatic and visceral fibers at the same relay neuron confuses the relationship between perceived and actual sites of pain. The pain is typically perceived at the somatic site, as somatic pain is well localized, whereas visceral pain is not.
From Thieme Atlas of Anatomy, Head and Neuroanatomy, © Thieme 2007, Illustration by Karl Wesker.
Inhibition of Pain
– Pain responses can be suppressed by descending pathways that synaptically inhibit the neurons of the ascending pain pathways. The periaqueductal gray matter (PAG) of the midbrain gathers information from higher centers and uses an indirect pathway to the dorsal horn that synaptically inhibits projection neurons.
– The neurons of the dorsal horn of the spinal cord, PAG, and amygdala are rich in opiate receptors. Stimulation of these receptor molecules by morphine induces presynaptic inhibition or postsynaptic hyperpolarization and results in analgesia.
The structure of the eye is shown in Fig. 5.7.
Fig. 5.7 Eye structure.
Sagittal section of the right eye viewed from the left.
Parallel rays coming from a point source of light at a distance > 20 feet are refracted (bent) by a convex glass lens so that the image is focused at a point behind the lens called the principal focus. The field of vision is inverted, and left to right is reversed on the retina.
– The focal length is the distance in meters from the lens to the principal focus.
– The refractive power of a lens is calculated in diopters (D):
D = 1/focal length
If the object is brought closer to the lens, the light rays are focused at progressively greater distances behind the principal focus.
When the ciliary muscle is relaxed in the normal (emmetropic) eye, parallel light rays are focused on the retina; that is, the retina lies at the principal focus of the eye. The diopteric power of the eye is ~60 diopters. Most of that refractive power is the result of light refraction at the interface of the air and the cornea. The remainder is contributed by the lens of the eye.
Accommodation allows the eye to focus on objects closer than 20 feet by increasing the curvature of the lens, thereby shortening the focal length. Lens curvature is controlled by the ciliary muscles, which receive parasympathetic innervation (fibers are derived from cranial nerve [CN] III). Muscle contraction counteracts a continuous stretch on the lens from the supporting ligaments (zonular fibers), allowing the lens to bulge more spherically for near vision (Fig. 5.8).
Fig. 5.8 Accommodation.
During accommodation for near vision, the ciliary muscles contract, allowing zonular fibers to relax and the lens to bulge. During accommodation for far vision, the zonular fibers are stretched, and the lens becomes flatter.
Optical defects occur due to refractive errors related to the curvature of the cornea or loss of accommodation. Table 5.3 summarizes optical defects, which are also illustrated in Figs. 5.9 and 5.10.
Fig. 5.9 Presbyopia, myopia, and hyperopia.
In presbyopia, the lens becomes less flexible, and the eye cannot focus on near objects. This can be corrected with a convex lens, but distant vision does not require correction. In myopia, the image is focused in front of the retina; this can be corrected with a biconcave lens. In hyperopia, the image is focused behind the retina; this can be corrected with a convex lens.
Fig. 5.10 Astigmatism.
In regular astigmatism, the curvature of the lens is asymmetrical in the horizontal and vertical axes. This abnormality can be corrected by a cylindrical lens.
The retinal circuit consists of three synaptically connected neurons: photoreceptor cells (rods or cones), bipolar cells, and ganglion cells (Fig. 5.11). Horizontal cells and amacrine cells are interneurons that link adjacent circuits for generating surround inhibition. All retinal cells, other than ganglion cells, are small neurons that do not transmit action potentials. Ganglion cells, whose axons form the optic nerve, are the only retinal cells that transmit action potentials.
Photoreceptor Cells: Rods and Cones. The eye contains 6 million cones that are clustered in the central region of the retina, known as the fovea centralis or macula, and 120 million rods that are mainly in the peripheral retina (Fig. 5.12).
Fig. 5.11 Layers of the retina.
Fig. 5.12 Photoreceptor cells.
Light-absorbing visual pigments and a variety of enzymes and transmitters in retinal rods and cones (1) mediate the conversion of light stimuli into electrical stimuli (phototransduction). The membranous disks of the retinal rods contain rhodopsin (2), a photosenstitive purple-red chromoprotein. Rhodopsin consists of the integral membrane protein opsin and 11-cis-retinal. Photic stimuli trigger a primary photochemical reaction in rhodopsin in which 11-cis-retinal is converted to all-trans-retinal (3). See also Fig. 5.13.
– Rods contain the light-absorbing pigment rhodopsin. They are responsible for vision at low levels of illumination and are not color sensitive. Black and white vision mediated by rods is called scotopic (or night) vision.
– Cones are responsible for color vision. There are three types of cones—red (long wave), green (medium wave), and blue (short wave), which each have different photopigments. Cones function at high levels of illumination and are responsible for photopic (or daytime) vision.
Photoreceptors in the dark have a membrane potential of about – 30 mV and tonically release the transmitter glutamate.
Adaptation to changes in light intensity
The eye adapts to changes in light intensity through pupillary aperture variation and by changes in retinal photoreceptor cells. Pupillary aperture variation alters the amount of light reaching the retina over a 30-fold range. It is mediated by the pupillary reflex with increased parasympathetic outflow to the iris constrictor muscle causing the pupil to constrict (miosis). Increased sympathetic outflow to the iris dilator muscle causes the pupil to dilate (mydriasis). With high levels of illumination, rods gradually become less sensitive to light. This is why it takes several minutes to adapt when entering a darkened theater. They are inactivated at high light intensities.
Macular degeneration is an age-related chronic eye disease that may affect one or both eyes. It tends to affect people over age 60 and has a slow, insidious onset. The most common type of macular degeneration is dry macular degeneration. It is caused by the buildup of yellow deposits, or drusen, on the macula, which damages the rods and cones. Symptoms of macular degeneration include blurriness or loss of central vision, which may manifest as difficulty reading and difficulty recognizing faces. People with this condition may notice that colors do not look as intense as they once did and that they take longer to adapt to dark environments. Macular degeneration is usually diagnosed at a standard eye examination when the drusen may be visualized on the retina. The patient is asked to look at an Amsler grid, which is composed of a grid of straight lines. People with macular degeneration may see these lines as faded, broken, or distorted. Angiography may also be used to detect this disease. There is no treatment that will reverse macular degeneration, but a high-dose formulation of vitamins, zinc, and antioxidants has been shown to slow disease progression.
The macula (fovea centralis) is the central region of the retina. It is extremely sensitive due to the following characteristics: it has a high concentration of cones that are closely packed; the overlying retinal layers diverge, permitting direct access of light to outer segments of the cones; and blood vessels detour around the fovea in order not to obscure reception.
Color blindness is the congenital absence of one of the color-type cones. It is a recessive X-linked characteristic, occurring in 2% of males. Red-green color blindness indicates the lack of either red- or green-sensitive cones and leads to confusion of these hues; the lack of blue-sensitive cones is rare. The more common color weakness (6% of males) is a decreased sensitivity of one or more cone systems. A protonope lacks red-sensitive cones, whereas a deuternope lacks green-sensitive cones.
Phototransduction in Rods
The disks in the outer segment of rods are studded with molecules of rhodopsin. Rhodopsin consists of a protein, opsin, linked to a chromophore, 11-cis-retinal. The cytoplasmic end of the rhodopsin molecule is coupled to a G-protein complex, transducin.
– In the dark, plasma membrane Na+ channels of the rod cell are held in the open position by cyclic guanosine monophosphate (cGMP).
Fig. 5.13 Process of phototransduction.
cGMP, cyclic guanosine monophosphate; 5′ GMP, 5′ guanosine monophosphate.
– A collision between a photon of light and a molecule of rhodopsin leads to the stereoisomerization (change in configuration) of 11-cis-retinal to all-trans-retinal (Figs. 5.12 and 5.13). This activates transducin, which in turn induces phosphodiesterase to become active. Phosphodiesterase breaks down the cGMP that is holding open the membrane Na+ channels, and the channels shut.
– As a result, the influx of Na+ ions is interrupted, and the membrane hyperpolarizes. This reduces the tonic release of glutamate at the synaptic ending of the photoreceptor.
– Each photoreceptor synapses with two types of bipolar cells: ON cells and OFF cells. Reduced release of glutamate by photoreceptors induces depolarization (disinhibition) of ON bipolar cells. Subsequently, a neurotransmitter is released from these bipolar cells, which causes the firing of ON ganglion cells (Fig. 5.14). A parallel network involving OFF bipolar cells causes inhibition of OFF ganglion cells.
Fig. 5.14 Potentials of photoreceptor cells, ON bipolar and ON ganglion cells.
Receptive Fields of Ganglion Cells and Surround Inhibition
Horizontal and amacrine cells connect bipolar cells to surrounding retinal circuits, resulting in surround inhibition. Thus, ganglion cell receptive fields consist of a center with an antagonist surround (e.g., ON center, OFF surround or vice versa) (Fig. 5.15).
Fig. 5.15 Receptive fields of ON ganglion cells and OFF ganglion cells.
ON ganglion cells (1,2) increase their firing when the center of their receptive field is illuminated and slow their firing when light strikes their surrounding periphery. OFF ganglion cells (3,4) fire more slowly when their center is illuminated and fire more rapidly when light strikes their periphery.
– The axons of ganglion cells form the optic nerve and optic tract. They convey information to the lateral geniculate body of the thalamus for processing.
– The left and right optic nerves undergo partial decussation at the optic chiasm, which is just anterior to the pituitary stalk. Optic nerve fibers arising from the nasal hemiretinas (central visual field) of each eye cross, whereas fibers of the temporal hemiretinas (nasal visual field) pass through the chiasm but remain ipsilateral.
– From the lateral geniculate, the information is relayed to the occipital cortex.
Lesions of Optical Pathways
Lesions of optical pathways will cause varying symptoms, depending on their location. The lettering in the following description refers to Fig. 5.16.
– Cutting the left optic nerve (A): This will cause blindness in the ipsilateral (left) eye.
– Cutting the optic chiasm (B): This will cause blindness in the temporal (nonnasal) halves of the visual fields of both eyes.
– Cutting the left optic tract (C): This will cause blindness in the right halves of the visual fields of both eyes.
– Cutting the left optic radiation (D): This will also cause blindness in the right halves of the visual fields of both eyes, but the foveal fibers remain intact so central vision is spared.
Visual Processing by the Cortex
Visual information is transformed to visual perceptions in the occipital lobe of the cortex. Foveal receptors occupy < 1% of total retinal area but project to ~50% of the primary visual cortex.
Fig. 5.16 Visual pathways and visual field deficits.
Cutting the left optic nerve causes blindness in the ipsilateral (left) eye (A). Cutting the optic chasm causes blindness in the temporal (nonnasal) halves of the visual fields of both eyes. (B). Cutting the left optic track causes blindness in the right halves of the visual fields of both eyes. (C). Cutting the left optic radiation will also causes blindness in the right halves of the visual fields of both eyes, but the foveal fibers remain intact so central vision is spared (D).
Receptive Fields of Cells in the Visual Cortex
There are three types of cells in the visual cortex. Each of these cells has a different receptive field pattern that causes them to respond preferentially to different types of visual stimuli:
– Simple cells have elliptically shaped receptive fields. An excitatory region may lie alongside or within the long axes of the ellipse parallel to an inhibitory region. Maximal activation occurs with stationary stimuli at the proper angle or orientation.
– Complex cells respond best to an edge stimulus in the receptive field with the edge at the preferred orientation, usually perpendicular to the long axis of the receptive field. Moving stimuli also have a preferred direction for optimal activation.
– Hypercomplex cells have a central excitatory field flanked by one or two inhibitory fields. They respond best to bars of optimum length moving in one direction along a preferred orientation.
This hierarchy may develop in a cascade of inputs from simple to more complex cells.
Atropine and the eye
Atropine is a competitive antagonist of acetylcholine (ACh) at muscarinic receptors. It causes sedation (by blocking M1 receptors), tachycardia and mild vasodilation (by blocking M2 receptors), and decreased gastrointestinal (GI) motility, urinary retention, and cycloplegia (paralysis of the ciliary muscle of the eye) with mydriasis (by blocking M3 receptors). Many of these effects are unwanted and are due to the low organ specificity of muscarinic antagonist drugs. Atropine analogues (homatropine or tropicamide) are used as ophthalamic solutions to produce mydriasis to allow retinal examination. Atropine is also used in the treatment of urinary incontinence, as a pre-anesthetic agent (for autonomic stability), to treat bradycardia in emergency situations, and as an antidote for cholinesterase inhibitor poisoning (e.g., insecticides).
Types of eye movements
The following are normal eye movements:
– Saccades are voluntary rapid flicks, or fast movements to shift the gaze.
– Smooth pursuit movements track or follow visual stimuli.
– Vestibular movements compensate for change in head orientation with body movements.
– Microtremors (microsaccades) are constant tiny involuntary movements during fixation, shifting the target image to unadapted receptors. If the target image were not shifted, it would fade by adaptation of receptors.
Nystagmus is a slow movement of the eyes in a particular direction (usually laterally) alternating with a quick recovery movement in the opposite direction. It is an alternation of a smooth pursuit movement and a saccade.
– Optokinetic nystagmus is a following reflex of the eyes to movement of the visual field. If the visual field moves to the right, then the eyes follow the field to the right (slow movement) and then recover to the left (fast movement).
Amblyopia (lazy eye), common in pre-school children, causes them to squint in an attempt to see more clearly. When they accommodate, their convergence is faulty, so they see two images (diplopia). The stronger eye suppresses the image from the weaker eye. If this is not corrected by surgery on the extraocular muscle and/or patching the dominant eye, the patient will develop cortical blindness in the weaker eye.
Primary open-angle glaucoma
Glaucoma refers to a group of eye diseases that cause damage to the optic nerve. Primary open-angle glaucoma is the most common form of glaucoma. In this case, drainage of the aqueous humor is prevented due to blockage of the drainage channels between the cornea and the iris. The buildup of aqueous humor results in raised intraocular pressure and subsequent damage to the optic nerve. Symptoms of this condition include gradual loss of peripheral vision that progresses to tunnel vision. Drug treatment is aimed at reducing intraocular pressure by decreasing the production of aqueous humor and/or increasing the drainage of the aqueous humor.
5.5 Hearing (Audition)
Physics of Sound
The sensation of sound is produced by vibrating air molecules striking the ear. The simplest sound waves are sinusoidal pressure waves with bands of condensation and rarification. They have defined amplitudes (measured in decibels [dB]) and defined frequencies (measured in cycles/sec [Hz]). The greater the amplitude of a sound wave, the greater the loudness. The greater the frequency, the higher the pitch.
Structure of the Ear
– Sound waves are channeled through the air-filled external auditory canal and cause the tympanic membrane (eardrum) to oscillate.
– The middle ear contains the three auditory ossicles (bones): the malleus, incus, and stapes (Fig. 5.17).
– The malleus inserts into the tympanic membrane.
– The incus connects the malleus to the stapes.
– The stapes inserts into the membrane covering the oval window of the cochlea, thereby conducting sound vibrations into the inner ear.
– The inner ear, or cochlea, is a bony tubular structure wound into a spiral of 2.5 turns (Fig. 5.17). Within the bony tube is an elongated, triangular membranous tube. The base of the triangle is the basilar membrane where the sensory receptor cells, of the ear, the hair cells, reside.
– These hair cells are innervated by afferent fibers of the auditory division of the vestibulocochlear nerve (CN VIII).
Fig. 5.17 Structures of the middle and inner ear and sound conduction.
Sound waves are transmitted to the organ of hearing via the external ear and the auditory canal, which terminates at the tympanic membrane (1). Vibration of the tympanic membrane is conducted by the ossicular chain (malleus, incus, and stapes) to the membrane of the oval window, where the inner ear begins. The inner ear consists of the vestibular organ and the cochlea. Inside the cochlea is an endolymph-filled duct called the scala media. The scala media is accompanied on either side by two perilymph-filled cavities: the scala vestibuli and the scala tympani (2). These cavities merge at the apex of the cochlea to form the helicotrema. The scala vestibuli arises from the oval window, and the scala tympani terminates on the membrane of the round window. The outer and inner hair cells that both sit upon the basilar membrane are the sensory cells of the hearing organ (3).
– The spiraling is unrelated to auditory perception but is a convenient configuration for supplying blood vessels and nerves to the cells of the inner ear.
– The space within the membranous tube is the scala media. It is filled with endolymph, which has a high K+ concentration.
– The space above the membranous tube is the scala vestibuli, and the space below the basilar membrane at the base of the tube is the scala tympani. They are filled with perilymph, which has a high Na+ concentration.
– The cell bodies of hair cells are fixed in the basilar membrane and extend into the tectorial membrane. The differences in elastic properties between these two membranes are important in auditory transduction.
The steps involved in auditory transduction are as follows:
1. Sound waves cause the tympanic membrane to vibrate.
2. Vibration of the tympanic membrane causes the ossicles to vibrate, which pushes the stapes against the oval window, generating pressure waves in the cochlea.
3. Pressure waves in the cochlea cause the basilar membrane to vibrate.
4. Vibration of the basilar membrane causes a shearing action between it and the tectorial membrane. The cilia of the hair cells connected to these membranes are bent to one side or the other as the tectorial membrane moves across the basilar membrane. This stimulates the opening of ion channels, increasing K+ permeability and initiating a receptor potential. Hair cell depolarization causes Ca2+ entry, which releases the neurotransmitter glutamate (Fig. 5.18).
Fig. 5.18 Stimulation of hair cells by membrane deformation.
Vibration of the cochlea causes a discrete shearing of the tectorial membrane against the basilar membrane, causing bending of the stereocilia of the outer hair cells (1). This bending causes mechanosensitive cation channels in the stereocilia membrane to open, allowing K+ to enter and depolarize the outer hair cells. This causes the outer hair cells to shorten. Repolarization is achieved by the opening of K+ channels on the perilymph side of the hair cell. The outflowing K+ is taken up by K+-Cl- cotransporters in the supporting cells and recirculated via gap junctions to the stria vascularis. The shortening of the outer hair cells changes the amplitude of the traveling sound wave, which then additionally bends the stereocilia of the inner hair cells. Depolarization occurs in the same way as for outer hair cells and causes the opening of basolateral Ca2+ channels, increasing the cytostolic Ca2+ concentration. This leads to the release of the neurotransmitter glutamate and the subsequent conduction of impulses in afferent neurons to the central nervous system (2,3). APs, action potentials.
– The large size of the tympanic membrane compared with the oval window has the effect of amplifying the pressure input into the cochlea.
– Inner hair cells detect sounds; outer hair cells sharpen the frequency response of the system, improving clarity.
– High sound frequencies cause maximum displacement of the basilar membrane at the basal end of the cochlea near the oval window. Low frequencies cause maximum displacement at the apical end.
– There is tonotopic organization of frequencies at all levels of the central auditory pathway. This occurs as a result of the displacement of a particular region of the basilar membrane by a particular range of frequencies. Each region is innervated by particular neurons, which preserve the tonotopic map.
– Auditory nerve fibers from the spinal ganglion terminate in the anterior and posterior cochlear nuclei.
– Secondary neurons cross, or project ipsilaterally, to the olivary nucleus. From there the neurons in the pathway continue to the lateral lemniscus, the medial geniculate, and finally the auditory cortex.
– Auditory signals use four to six neurons to project from the cochlea to the auditory cortex.
– Projections are mainly contralateral but also unilateral. Consequently, binaural hearing is still possible in the presence of unilateral lesions to higher relays or the auditory cortex.
Auditory Processing by the Cortex
The auditory cortex processes information from neural inputs:
– Discriminate pitch (frequency): the auditory system can discriminate 1 dB of sound pressure difference at low intensities and even lower sound pressure differences at higher intensities. A particular auditory neuron responds best to a limited range of frequencies. Surround and lateral inhibition produce sharper pitch discrimination.
– Localize sound sources in space: the input to auditory neurons is often inhibitory from one ear and excitatory from the other. The amount of lag time can be used for low frequencies, whereas intensity is used for high frequencies.
– Recognize patterns of sounds: neurons are more sensitive to changes of pitch and intensity at higher relay centers. They respond only to increasingly complex sound patterns as activity ascends toward the cortex.
5.6 The Vestibular System
Structure and Function of the Vestibular System (Fig. 5.19)
– The sensory ridges (ampullary crests) of three endolymph-filled semicircular canals, which are oriented in different planes, detect angular acceleration (e.g., nodding, tilting, and rotating of the head).
– The sensory maculae of the saccule and utricle in the petrous bone detect linear acceleration and changes in direction of gravity relative to the head.
– The sensory cells of both the ampullary crests and the maculae are hair cells. Two types of cilia, a long kinocilium and many shorter stereocilia, extend from these hair cells. These hair cells are spontaneously active. Movement of the cilia in response to movement of the endolymph (due to angular or linear acceleration) is either excitatory or inhibitory depending on direction.
Fig. 5.19 provides greater detail on how endolymph movement results in ciliary movement.
Fig. 5.19 The vestibular system.
(1) This system consists of three semicircular canals with sensory ridges (ampullary crests) and the saccule and utricle with sensory maculae. (2) Ampulla, dilated portions of the canals (shown in cross-section), contain connective-tissue ridges, the ampullary crests, each with sensory cells that are encased in a gelatinous cupula, which extends from the crest and attaches to the roof of the ampulla. Sensory cells on the crest extend into the cupula and bear on them one kinocilium and many shorter stereocilia. When the head is rotated in the plane of one of the canals, the lag of the endolymph causes a deflection of the cupula, which causes bending of the cilia. (3) The sensory cells are either hyperpolarized (inhibitory) or depolarized (excitatory) depending on the direction of ciliary motion. (4) The saccular and utricular maculae are areas of the epithelial lining that contain arrays of sensory cells. These cells also bear a kinocilium and stereocilia which project to an otolithic membrane. The latter consists of a gelatinous layer similar to the cupula but with otoliths, calcium carbonate crystals, embedded in it. The crystals exert traction on the gelatinous mass in response to linear acceleration, inducing shearing motions in the cilia with similar results to those found for the sensory cells on the ampullary crests (3). The afferent fibers that synapse with the sensory cells carry the messages to the vestibular ganglion.
Nystagmus is a slow movement of the eyes in a particular direction (usually laterally) alternating with a quick recovery movement in the opposite direction. It is an alternation of a smooth pursuit movement and a saccade.
– Caloric nystagmus is elicited by placing cool or warm water in the external ear. The resultant thermal convection currents stimulate the semicircular canals. Cool water produces nystagmus with slow recovery to the opposite side as the ear being tested. Warm water produces nystagmus with a quicker recovery to the same side as the ear being tested.
The integrity of the vestibular system is tested by inducing caloric nystagmus and looking for the results described, which demonstrate that the vestibular neural pathways are intact.
Afferent fibers from utricle, saccule, and semicircular canals synapse in vestibular nuclei in the brainstem; they also project to the cerebellum. The vestibular nuclei have major connections to the oculomotor system for stabilizing the visual image, to the neck muscles for stabilizing the head, and to the postural muscles for body balance.
Mechanisms of damage protection in the ear
The linkage of ossicles is protected from damage due to loud sounds by an attenuation reflex mediated through an efferent inhibitory system. This reflexively contracts the tensor tympani and stapedius muscles when a loud sound is heard. However, the reflex has a 40 msec latency, so there is no protection for fast transient sounds of high intensity (e.g., a thunder clap). The eustachian tube is a pressure relief system that maintains equal pressure on both sides of the eardrum. Abrupt changes in atmospheric pressure cause a popping sensation due to air moving in or out of the eustachian tube.
Ototoxic drugs are those that are harmful to the auditory nerve, cochlea, and vestibular system. Examples of ototoxic drugs include gentamicin, streptomycin, aspirin (in high doses), and furosemide. Damage caused by these drugs may be temporary and will subside when the drug is stopped, or it may be permanent. Symptoms of ototoxicity may be tinnitus (ringing in the ears), hearing loss, and vertigo.
Vertigo is the illusion of movement. It is most commonly caused by disorders of the inner ear such as Meniere disease (a syndrome characterized by vertigo, tinnitus, and deafness), vestibular neuronitis, lesions involving CN VIII, head injury causing vestibular damage, benign postural vertigo (vertigo occurs when certain positions are adopted or movements made), and drugs (e.g., gentamicin, barbiturates, and alcohol). Other causes of vertigo are migraine, epilepsy, multiple sclerosis, and tumors. Treatment depends on the cause, but anti-cholinergic drugs and antihistamines are often used to prevent nausea and vomiting.
Deafness in adults
Conduction deafness occurs when there is impaired transmission of sound through the auditory canal to the auditory ossicles. Causes of conduction deafness include earwax, ear malformations, perforation of the eardrum due to trauma or infection, damage to the ossicles (trauma or infections), and tumors that block the eustachian tube.
Sensorineural deafness occurs when there is damage to the cochlea and cochlea nerve. Causes include ototoxic drugs, infections (e.g., flu, herpes, and mumps), and Meniere disease.
Presbycusis is the loss of high-frequency hearing with aging. It is likely due to damage to the hair cells closest to the oval window from loud exposure to sounds.
Rinne test: With normal hearing, air conduction (as determined by a tuning fork held laterally to the external auditory meatus) is better than bone conduction (tuning fork placed on the mastoid process). Rinne-positive results (air conductance > bone conductance) occurs with normal ears and sensorineural (perceptive) deafness. Rinne-negative results (bone conductance > air conductance) are seen in conduction deafness.
Weber test: The foot of the tuning fork is placed in the middle of the patient’s forehead, and the patient is asked in which ear the sound is heard. Sound localizes to the affected ear with conduction deafness, to the contralateral ear in sensorineural deafness, and is perceived as equally loud in both ears if both ears are normal.
5.7 Taste (Gustation)
Taste Receptor Cells
On the dorsal surface of the tongue, there are four types of lingual papillae: filiform, fungiform, vallate, and foliate. The latter three types have taste buds on their surface (Fig. 5.20). Taste receptor cells are located within taste buds. The microvilli at the apical surface of the receptor cells come in contact with taste molecules dissolved in saliva. On their basal surface, they synapse with gustatory afferent fibers.
The five primary taste qualities are as follows:
– Salty taste: evoked by cations such as Na+
– Sour (acid) taste: evoked by H+ ions
– Bitter taste: evoked by alkaloids
Fig. 5.20 Structure of a taste bud.
Nerves induce the formation of taste buds in the oral mucosa. Nerve fibers (from cranial nerves VII, IX, and X) grow into the oral mucosa at the basal side and induce the epithelium to differentiate into taste cells. These cells have microvilli that extend to the gustatory pore.
– Sweet taste: evoked by certain organic compounds (sugars and amino acids)
– Umami (meaty) taste: evoked by amino acids
It is believed that every taste can be duplicated by proper mixing of the five primary taste qualities.
– Salty taste results from the potential changes that follow entry of Na+ through Na+ channels on the microvilli of taste receptor cells. Sour taste also results from the direct effects of protons on membrane channels.
– Sweet taste is the result of activation of second messengers by a G protein (gustducin) coupled to a protein receptor in the membrane. Bitter taste likewise uses a second messenger cascade.
– The mechanism for tasting umami is unknown.
Membrane potential changes on taste receptor cells result in the release of transmitter and subsequent generation of action potentials in taste afferents.
Three cranial nerves carry taste information to the CNS:
– The chorda tympani of the facial nerve (CN VII) innervates taste buds on the anterior two thirds of the tongue.
– The glossopharyngeal nerve (CN IX) innervates taste buds on the posterior one third of the tongue.
– The vagus nerve (CN X) innervates scattered taste buds of the oropharynx and epiglottis.
Taste information from these cranial nerves is gathered at the solitary tract nucleus of the medulla. From there information flows to the ventral posteromedial nucleus of the thalamus and subsequently to the face area of the postcentral gyrus. Other targets are the hypothalamus, amygdala, and insular cortex (Fig. 5.21).
Taste Processing in the Central Nervous System
Each taste afferent can respond to more than one of the primary taste qualities. Although individual fibers respond preferentially to one or two of these qualities, gustatory coding is not a strictly labeled line system. Instead, the CNS must analyze taste stimuli based on a cross-fiber pattern code.
Fig. 5.21 Gustatory pathways.
Olfactory Receptor Neurons
– Olfactory receptor neurons (ORNs) are bipolar neurons located in the olfactory epithelium. In contrast to taste receptor cells, these cells are themselves neurons whose axons extend into the CNS.
– The basal cells of the olfactory epithelium are adult stem cells that continuously divide and differentiate into ORNs. Because the olfactory epithelium is exposed to harmful gases and airborne pathogens, resulting in cell death, there must be continual cell turnover in this epithelium.
Odorant molecules bind to ORNs on 1 of roughly 400 different sensory cell types. The activated receptor stimulates Gs proteins, causing an increase in cyclic adenosine monophosphate (cAMP) and opening of Na+ or Ca2+ channels. This, in turn, causes membrane depolarization (Fig. 5.22).
Axons of the olfactory sensor cells penetrate the bony cribriform plate in the nose to synapse on mitral and bristle cells and inhibitory interneurons in the olfactory bulb. The olfactory bulb also receives descending efferent input from the olfactory cortex. Axons from mitral and bristle cells project as the olfactory tract to the prepiriform cortex directly or via the thalamus and to the amygdala and hypothalamus.
Fig. 5.22 Transduction of olfactory stimuli.
(ATP, adenosine triphosphate; cAMP, cyclic adenosine monophosphate; GTP, guanosine triphosphate; ICF, intracellular fluid)