### Human Skin The human skin is the largest organ of the human body. **Somatosensory System Functions** - **Exteroceptive Functions - **Mechanoreception** - pressure or touch (**tactile** sensitivity) - **Thermoreception** - temperature (**thermal** sensitivity) - **Nociception** - noxious (damaging or potentially damaging) stimuli (**noxious** sensitivity). Noxious stimulus refers to the capacity of a stimulus of injuring our skin, regardless if it is painful or not. - **Proprioceptive Functions (Kinaesthesis)** - information about position and movement of limbs and body in space. - **Interoceptive Functions** - information from internal organs. **Mechanoreception** - **Form Perception** (pressure is part of form perception) - E.g., identification of objects by touch alone; Braille reading; measured experimentally in terms of "two-point threshold" (minimal distance between the stimuli need to feel that there are 2 pencils pressing on your skin). - Note (Huge) variation in sensitivity across skin surface. - **Texture Perception** - Our ability to analyse surfaces by touching them which is closely associated with vibration perception. Texture perception is very important for rodents. - **Vibration Perception** - Flutter (frequencies \< 40 Hz) - Vibration (frequencies 40 -- 400 Hz) **Skin and Skin Receptors** ![[ETH/ETH - Systems Neuroscience/Images - ETH Systems Neuroscience/image45.png]] There are many different types of receptors in the skin (number is still debated), the skin is a huge organ (large surface) filled with receptors. - Size of skin as receptor surface - **Glabrous** (hairless) and **Hairy skin**. - Distinctions between: - **Encapsulated** and **Unencapsulated** receptors - **Superficial (cutaneous)** and **Deep** receptors. (The location in the skin give them a different type of sensitivity. At the base of the hair follicle, we have some nerves wrapped around the hair. Just below the epidermis, we have Merkel's disk, free nerve ending and Meissner's corpuscle. Deeper layers of the skin have the Pacinian corpuscle and Ruffini's endings. - **Superficial Encapsulated Receptors**: - Merkel Receptor/Disk - Meissner Corpuscle - **Deep Encapsulated Receptors**: - Ruffini Ending - Pacinian Corpuscle - **Unencapsulated Receptors** - free nerve endings. Because of their location in the skin and the nature of their specializations, different encapsulated receptor types have different forms of cutaneous sensitivity. This was first discovered not by looking at receptors themselves but by recording from **single Cutaneous Afferent Fibers** (can be done in humans and in animals, e.g., Swedish researcher sticking electrodes in his arms). All of the mechanoreceptor afferent axons are medium diameter (6 -- 12 μm), well-myelinated fibers with conduction velocities of 35-75 m/s. They are called **Aβ Fibers**. **Cutaneous Afferents** Some of these receptors quickly adapt, while others don't. Fibers are classified as either: - **Rapidly Adapting (RAs)** - **Slowly Adapting (SAs)** - Also in terms of the size of their **Receptive Field** (The size of the area on the skin from which they can be activated) (it is also related to the position of the receptor, indeed superficial receptors tend to have smaller RF than deeper ones). ![[ETH/ETH - Systems Neuroscience/Images - ETH Systems Neuroscience/image46.png]] A **stimulus probe movement** consists of applying a pressure through a probe on the skin and subsequent release. In the picture above, we can notice that the top row adapts very fast to the pressure stimulus and signal it. Ruffini's endings on the contrary never completely adapts to the new stimulus and doesn't stop firing. **Schematic Illustration of Determination of Receptive Field** |![[ETH/ETH - Systems Neuroscience/Images - ETH Systems Neuroscience/image47.png]] | ![[ETH/ETH - Systems Neuroscience/Images - ETH Systems Neuroscience/image48.png]] | |---|---| As we can see from the picture, Meissner's corpuscles tend to have small RF. On the contrary, Pacinian corpuscles are relatively deep and have large receptive fields. **RAs** respond only at the beginning and end of sustained displacements (i.e., to transients) but respond well to higher frequency vibrations. Two types: - **RA I: Meissner Corpuscles** (10 - 200 Hz) (small RF) - **RA II: Pacinian Corpuscles** (70 - 1000 Hz) (large RF) **SAs** respond throughout sustained displacements of the skin, and are thus suited to coding the duration and magnitude of mechanical stimuli. Two types: - **SA I: Merkel Receptors/Disks** (small RF) - **SA II: Ruffini Endings** (large RF) Encapsulation has a very important role to play. The sensitivity characteristics of a particular afferent fiber reflects the specialized nature of the encapsulated ending (e.g., If you dissect away the onion-like layers of a PC, the fiber from that PC becomes sensitive to sustained displacement) and its position on the skin. By removing the capsule and leaving only the axon, they realized that the receptor potential was relatively different, to the point of changing a fast-adapting receptor to a slowly adapting one. Papers show that these properties are due to the mechanical properties of this structure. **Summary Classification Table** ![[ETH/ETH - Systems Neuroscience/Images - ETH Systems Neuroscience/image49.png]] **Hairy Skin** - Merkel disks, Pacinian corpuscles and free nerve endings as in glabrous skin. While Ruffini's endings and Meissner's corpuscles are less common in hairy skin. - Innervation of hair follicles (by free nerve endings or more specialized endings). - A recent discovery -- hairy skin has "soft touch" receptors that project to cortical regions associated with emotion and sexual arousal. **Nociception** - Nociceptors respond to noxious mechanical and thermal stimuli (i.e., stimuli that produce or threaten to produce tissue damage) and also to chemicals released by damaged tissue (e.g., histamine, etc.). - Note distinction between noxiousness as a quality of the stimulus and pain as perceptual and emotional response. - Two types of nociceptor: - **High Threshold Mechanoreceptors** - **Polymodal Nociceptors** - Receptors are **free nerve endings.** - Afferent axons are of different types (which have very different conduction velocities): - **High Threshold Mechanoreceptors: Aδ Fibers.** - **Polymodal Nociceptors: C Fibers.** Axon types in nerves from skin and from muscles (Note different terminologies associated with different origins). ![[ETH/ETH - Systems Neuroscience/Images - ETH Systems Neuroscience/image50.png]] Different fiber types give rise to different pain sensations: - "First" or "Cutaneous Pricking" pain - mediated by **Aδ Fibers**. - "Second" or "Burning" pain - mediated by **C Fibers**. ![[ETH/ETH - Systems Neuroscience/Images - ETH Systems Neuroscience/image51.png]] **Thermoreception** - Thermoreceptors: "**Warm**" fibers and "**Cold**" fibers. - They respond to increase or decrease in temperature, respectively, from steady state and to maintained temperature. - At intermediate skin temperatures (approx. 30-35 degrees) there is ongoing discharge in both warm and cold fibers, and a change in skin temperature reciprocally modifies the discharge in the two fiber types. At a lower adapting temperature (e.g., 26 degrees) only cold fibers are active, and an increase in temperature first decreases the discharge in cold fibers, and then - with larger increments - begin to engage the previously silent warm fibers. - Large receptive fields, so temperature sensations are not well localized. - Note relativity of thermal sensations (i.e., change in temperature is what is felt as warm or cold) and similar relativity of neuronal responses. (Three buckets of water experiment) - Receptors are free/bare nerve endings. - Afferent axons: - **Warm Fibers**: **C Fibers** - **Cold Fibers: Aδ Fibers** **Proprioception (The Kinaesthetic Sense)** - Provides information about the position and movement of the limbs and body in space (e.g., limb movement without vision; passive movement). - Proprioceptive information supplements "efference copy" (It refers to perform precise, well-coordinated movements) information from motor system. - Information is provided by three classes of receptors: - **Cutaneous Mechanoreceptors** - **Joint Receptors** - **Muscle Spindles** (Muscle fibers that are measuring the state of tension of the muscle) and **Golgi Tendon Organs** **Cutaneous Mechanoreceptors** and **Joint Receptors** - **Cutaneous Mechanoreceptors** - Information about skin stretch from Ruffini/SAII afferents. - Of different importance in different regions (important around hands, mouth and feet). - **Joint Receptors** - Ruffini-type endings and Pacinian corpuscles in joint capsule. - But not essential, because anesthesia or removal of joint capsules does not result in loss of limb position sense (they seem to be supplementary). **Muscle Spindles** and **Golgi Tendon Organs** - Golgi tendon organs (**Ib** fibers) respond to tendon stretch. - Muscle spindles (type **Ia** and **II** axons) are coiled around intrafusal muscle fibers; respond to muscle stretch; type I axons constitute the sensory component of the knee-jerk reflex. **Dorsal Root Ganglia** ![[ETH/ETH - Systems Neuroscience/Images - ETH Systems Neuroscience/image52.png]] All somatic fibers are the axons of dorsal root ganglion cells (or trigeminal ganglion cells in the case of the head and neck). DRG cells have no dendrite, but a single bifurcating axon - sends one process to the periphery and another to the CNS. **Dermatomes** ![[ETH/ETH - Systems Neuroscience/Images - ETH Systems Neuroscience/image53.png]] The axons of individual dorsal root innervate a restricted region of skin that is the same in everyone -- **dermatome**. A **dermatomal map** is a stereotyped pattern of dermatomes that allows for diagnosis of location of injury or infection of dorsal roots on basis of skin distribution of sensitivity (e.g., in shingles). ### Modality Segregation It is the basic principle of organization of the somatosensory system. Information from each class of receptors reaches a different group of neurons in the CNS and these neurons project to higher levels along segregated "parallel" pathways. This segregation begins with the place of termination of different classes of afferent axon in the spinal cord. It continues with two major ascending pathways: - **The Dorsal Column -- Medial Lemniscal Pathway** - **The Spino -- Thalamic Pathway** (pain & temperature information) **Segregation in Spinal Cord** - The spinal grey matter is divided into a number of layers (laminae); laminae I -- VI comprise the dorsal horn. - Aδ and C fibers terminate predominantly in layer I (the marginal layer) and layer II (the substantia gelatinosa). - Aδ axons bifurcate, one branch ascending in the dorsal columns, the other terminating on cells in the deeper dorsal laminae. ### The Dorsal Column - Medial Lemniscal Pathway - The ascending branches of **Aβ axons** (conveying discriminative touch information, i.e., carrying mechanoreceptive information) ascend in the dorsal columns (the **gracile and cuneate fasciculi)**, and synapse on cells in the **dorsal column nuclei (DCN)** in the medulla (the **gracile** and **cuneate** nuclei, respectively). - The axons of DCN cells cross the midline and ascend in the **medial lemniscus** to the **lateral division of the ventro-posterior nucleus (VPL)** of the thalamus. - **VPL** cells in turn project to the primary somatosensory cortex (**SI**). **The Dorsal Column System** ![[ETH/ETH - Systems Neuroscience/Images - ETH Systems Neuroscience/image54.png]] **Things to Note About Dorsal Column -- Medial Lemniscal Pathway** - The **Gracile Fasciculus** extends the entire length of the spinal cord; it and the **Gracile Nucleus** contain a representation of the feet, legs, and lower trunk. - The **Cuneate Fasciculus** begins at the cervical level; it and the **Cuneate Nucleus** contain a representation of the hands, arms, and upper trunk. - The entire system is topographically organized (i.e., adjacent parts of the body surface are represented by adjacent neurons - **Somatotopy**). - The decussation (crossing over) of the medial lemnisci results in a representation of the **contralateral** body surface on each side of the brain at levels above the DCN. ### The Spino - Thalamic Pathway - It represents the second-major pathway. - Small-diameter myelinated and unmyelinated axons (**Aδ** and **C**) fibers serving temperature sensitivity and nociception) terminate in the spinal cord itself. - The axons of the spinal neurons then cross the midline and ascend as **the anterolateral system**. - Most of these fibers (constituting the **spino-thalamic system**) terminate in VPL and in the intralaminar and posterior groups of thalamic nuclei. - Other ascending fibers terminate in the reticular formation (the **spino-reticular system**) and in the midbrain. - The VPL neurons receiving spino-thalamic input are segregated from those receiving medial lemniscal input and project to both primary and secondary somatosensory cortex (**SI** and **SII**). **The Spino - Thalamic System** ![[ETH/ETH - Systems Neuroscience/Images - ETH Systems Neuroscience/image55.png]] Note that the drawing is inaccurate with respect to the location of the cell body in the cord - it should be in lamina I or II. **Schematic Representation** of **Dorsal Column-Medial Lemniscal** and **Spino-Thalamic Pathways** ![[ETH/ETH - Systems Neuroscience/Images - ETH Systems Neuroscience/image56.png]] When people have lesions in the spinal cord, they will lose all the mechanoreceptive information associated with parts of the body below the lesion for Dorsal Column - Medial Lemniscal Pathway. **Schematic Illustration** of the **Location** of the **Major Thalamic Nuclei Involved** in the **Processing of Somatosensory Information** ![[ETH/ETH - Systems Neuroscience/Images - ETH Systems Neuroscience/image57.png]] ### The Trigeminal System - It is dedicated to the brain and the neck. - Conveys somatosensory input from the face. - Large-diameter myelinated axons of the trigeminal ganglion conveying discriminative touch information terminate in the principal trigeminal nucleus. - The axons of these cells then cross the midline, join the medial lemniscus, and terminate in the **medial division of the Ventro-Posterior Nucleus (VPM)**. - Small diameter lightly-myelinated and unmyelinated axons of the trigeminal ganglion conveying thermal and nociceptor information descend in the spinal trigeminal tract and terminate in the spinal trigeminal nucleus. - The axons of these cells then project to VPM and to the posterior and intralaminar thalamic nuclei (i.e., rather like the anterolateral system). - Hence, we have a separation again of mechanoreceptors from thermoreceptors. ### The Somatosensory Thalamus - The **ventrobasal** complex of the thalamus has the two major divisions previously described: - **VPL** (somatosensory information from the body) - **VPM** (somatosensory information from the face) - Both are somatotopically organized. - Thalamic neurons have adaption properties (SA vs RA) like those of peripheral neurons, but the RFs are larger than those of dorsal root ganglion cells and are commonly concentric, with a central excitatory area and a surrounding inhibitory area. ![[ETH/ETH - Systems Neuroscience/Images - ETH Systems Neuroscience/image58.png]] ### Somatosensory Cortex - Two major areas in primates - **SI** - on posterior bank of central sulcus and crown of post-central gyrus. - **SII** - on lip and upper bank of lateral fissure. - SI contains 4 distinct areas (**3a, 3b, 1, and 2**) with different characteristics and functions: - Areas 3a and 3b receive most of the direct projections from the thalamus and in turn project to areas 1 and 2. - Areas 3b and 1 receive input from skin receptors. - Areas 3a and 2 receive input from joint and muscle receptors. - Effects of cortical lesions: - Large lesions of all of SI produce deficits in position sense and in discrimination of size, texture and shape. They also produce motor deficits in hand function. (Link between somatosensory information and motor-commands). - Area 3b lesions result in severe deficits in tactile discrimination of texture, size and shape. - Area 1 lesions affect texture but not size discrimination. - Area 2 lesions affect size and shape but not texture discrimination. **Cortical Receptive Fields** - Receptive fields in area 3b, like those in the thalamus, are larger than those of DRG neurons and typically have excitatory centre - inhibitory surround structure. - Receptive fields in "higher" cortical areas are larger than those in 3b, and many are much more complex (e.g., sensitive to the orientation of an edge (cf. visual cortex), the direction of movement across the skin, or the surface curvature of objects). - Some neurons in area 2 are selective for the 3-dimensional shape of objects. ![[ETH/ETH - Systems Neuroscience/Images - ETH Systems Neuroscience/image59.png]] **Cortical Somatotopy** - Human somatotopy - classic map ("homunculus") based on cortical stimulation (produced by Penfield). - Distorted nature of homunculus. - Differences between species (enlarged representation of face and facial vibrissae in rodents (the "musunculus")). - Neurophysiological evidence in monkeys indicates that each of the 4 areas comprising SI is somatotopically organized (i.e., a "full homunculus" for each one of these regions). - Note that multiple representations of the receptor surface are a common feature of all sensory cortices. - Note that representations are commonly "mirror-reversed" across field boundaries. **Columnar Organization** - Neurons in a "column" running orthogonal to the cortical surface and through the cortical layers have very similar RFs and modality properties (including adaptation rate). - A cortical column is approx. 300 - 600 μm in diameter. - Columnar organization was first described in detail by Mountcastle and his colleagues in somatosensory cortex and is now recognized as one of the fundamental principles of the organization of sensory cortex.