Neuroscience Past Paper PDF

SENSORY FUNCTIONS Be able to describe the different types of specialized sensory cells / receptors for the different sensory modalities (touch, proprioception, pain, vision, hearing, balance/spatial orientation, taste and smell), and describe their anatomical and histological or...

SENSORY FUNCTIONS Be able to describe the different types of specialized sensory cells / receptors for the different sensory modalities (touch, proprioception, pain, vision, hearing, balance/spatial orientation, taste and smell), and describe their anatomical and histological organization Be able to explain, for the different sensory modalities, how specialized sensory cells / receptors transduce a stimulus into electrical signals Be able to define the central pathways conveying sensory information from the different parts of the body Be able to explain, for the different sensory modalities, how sensory information is processed in specific brain regions Be able to explain how we perceive different sensory stimuli and how they can be modulated Hearing Sound is a wave described with frequency (pitch), and amplitude (loudness, decibels). A sound of 150 dB would cause eardrum rupture. We can detect frequencies from 20 Hz to 20000. Outer ear directs sound, consists of pinna concha, and auditory meatus. Middle ear is an air filled cavity in the temporal bone that transmits vibrations of the tympanic membrane to the inner ear. The major function of the middle ear is to match relatively low- impedance airborne sounds to the higher-impedance fluid of the inner ear. It has both an amplification mechanism (thanks to force impinging on the relatively large-diameter tympanic membrane onto the much smaller-diameter oval window, and a second and related process relies on the mechanical advantage gained by the lever action of the three small, interconnected middle ear bones, or ossicles which connect the tympanic membrane to the oval window) and an attenuation mechanism for loud sounds (thanks to the tensor tympani, and the stapedius. Contraction of these muscles, which is triggered automatically by loud noises or during self- generated vocalization, counteracts the movement of the ossicles and reduces the amount of sound energy transmitted to the cochlea, serving to protect the inner ear). The inner ear is the site where the energy from sonically generated pressure waves is transformed into neural impulses. The cochlea of the inner ear is the site where the energy is transformed from sonically generated to neural impulses, and it also acts as a mechanical frequency analyzer, decomposing complex acoustical waveforms into simpler elements. Many features of auditory perception accord with aspects of the physical properties of the cochlea; hence, it is important to consider this structure in some detail. The cochlea is bisected from its basal end almost to its apical end by the cochlear partition, a flexible structure that supports the basilar mem brane and the tectorial membrane. There are fluid- filled chambers on each side of the cochlear partition, called the scala vestibuli and the scala tympani. A distinct channel, the scala media, runs within the cochlear partition. The cochlear partition does not extend all the way to the apical end of the cochlea; instead, an opening known as the helicotrema joins the scala vestibuli to the scala tympani, allowing their fluid, known as perilymph, to mix. The traveling wave in the cochlea that propagates from the base toward the apex of the basilar membrane, growing in amplitude and slowing in velocity until a point of maximum displace ment is reached. The point of maximum displacement is determined by the frequency of the stimulus and persists vibrating in that pattern as long as the tone endures. The points responding to high frequencies are at the base of the basilar membrane, and the points responding to low frequencies are at the apex, giving rise to a topographical mapping of frequency. The traveling wave initiates sensory trans duction by displacing the sensory hair cells that sit atop the basilar membrane. Because the basilar membrane and the overlying tectorial membrane are anchored at different positions, the vertical component of the traveling wave is translated into a shearing motion between these two membranes. This motion bends the tiny processes, called stereo cilia, that protrude from the apical ends of the hair cells, leading to voltage changes across the hair cell membrane. How the bending of stereocilia leads to receptor potentials in hair cells is considered in the following section. The cochlear hair cells in humans consist of one row of inner hair cells and three rows of outer hair cells. The inner hair cells are the sensory and the terminations on the outer hair cells are almost all from efferent axons that arise from cells in the superior olivary complex. The hair cell is a flask-shaped epithelial cell named for the bundle of hairlike processes that protrude from its apical end into the scala media. Each hair bundle contains anywhere from 30 to a few hundred stereocilia, with one taller kinocilium. Displacement of the hair bundle parallel to the plane of bilateral symmetry in the direction of the tallest stereocilia stretches the tip links, directly opening cation-selective mechanoelectrical transduction (hair cell MET or hcMET) channels located at the end of the link and depolarizing the hair cell. Movement in the opposite direction compresses the tip links, closing the hcMET channels and hyperpolarizing the hair cell. As the linked stereocilia pivot back and forth, the tension on the tip link varies, modulating the ionic flow and resulting in a graded receptor potential that follows the movements of the stereocilia. This receptor potential in turn leads to transmitter release from the basal end of the hair cell, which triggers action potentials. The transduction of mechanical forces by hair cells is both fast and remarkably sensitive. An unusual adaptation of the hair cell in this regard is that K+ serves both to depolarize and repolarize the cell, enabling the hair cell’s K+ gradient to be largely maintained by passive ion movement alone Because a single auditory nerve fiber innervates only a single inner hair cell each auditory nerve fiber transmits information about only a small part of the audible frequency spectrum. As a result, auditory nerve fibers related to the apical end of the cochlea respond to low frequencies, and fibers that are related to the basal end respond to high frequencies. Place Principle Definition: The place principle is based on the tonotopic organization of the cochlea, where different regions of the basilar membrane are sensitive to specific frequencies. Mechanism: o High-frequency sounds stimulate the base of the cochlea, where the membrane is stiff and narrow. o Low-frequency sounds stimulate the apex, where the membrane is wider and more flexible. Relevance: Encodes sound frequencies above approximately 4 kHz, where phase locking becomes less effective. 2. Phase Locking Definition: Phase locking occurs when auditory nerve fibers fire action potentials in synchrony with the phase of a sound wave. A neuron can "fire" (send a signal) every time the wave reaches a specific point, like the peak (highest part) of the wave. At higher frequencies, the waves move too fast for neurons to keep up. Mechanism: o Neurons respond at specific points of the sound wave cycle, typically the peaks. o Effective for encoding frequencies up to 1–4 kHz because neurons cannot fire fast enough to match the phase of higher-frequency sounds due to their refractory period. Relevance: Provides precise timing information about low-frequency sounds. Location of sounds We can infer the location of a sound source by comparing the sound input of the two ears (time (arrives before or after depending on location in one ear, sound can arrive at different phases, and this works worse for high frequency sounds) and intensity (Interaural intensity difference (IID): The head creates a "shadow" for high-frequency sounds, reducing their intensity when they reach the ear farthest from the sound source)). Within the cochlear nucleus, each auditory nerve fiber branches, sending an ascending branch to the anteroventral cochlear nucleus and a descending branch to the posteroventral cochlear nucleus  and the dorsal cochlear nucleus. The circuits that compute the position of a sound source on this basis are found in the lateral superior olive (LSO) and the medial nucleus of the trapezoid body (MNTB). Primary auditory cortex corresponds to Broadmann’s area and send projection to auditory association area (discrimination of sound patterns and Wernicke’s area, involved in language comprehension). Vestibular system It is a key component in postural reflexes and eye movements and, in concert with the visual and proprioceptive systems, plays a central role in distinguishing self-generated “active” movements of the head and body from passive movements resulting from externally applied forces. This multimodal integration is critical to our perception of self-motion, spatial orientation, and body representation.  The main peripheral component of the vestibular system is an elaborate set of in terconnected chambers—the labyrinth thata uses the hair cells to transduce motion into neural impulses. The pertinent motions arise from the effects of gravity and from translational and rotational movements of the head. The labyrinth is buried deep in the temporal bone and consists of the two otolith organs—the utricle and saccule—and three semicircular canal. The utricle and saccule are specialized primarily to respond to translational movements of the head and static head position relative. to the gravitational axis (i.e., head tilts), whereas the semicircular canals, as their shapes suggest, are specialized for responding to rotations of the head. The vestibular hair cells are located in the utricle and saccule and in three jug like swellings called ampullae, located at the base of the semicircular canals next to the utricle. For hair cells, is the same as with depolarizing or hyperpolarizing the cells. Adaptation in vestibular hair cells, mediated by calcium entering through mechanoelectrical transduction (MET) and voltage-gated calcium channels, is especially important to vestibular function, as it allows hair cells to continue to signal small changes in head position despite much larger tonic forces of gravity. The two otolith organs, the utricle and the saccule, de tect tilting and translational (i.e, linear, as opposed to rotational) movements of the head. They contain the macula, which consists of hair cells and associated supporting cells. Overlying the hair cells and their hair bundles is a gelatinous layer; above this layer is a fibrous structure, the otolithic membrane, in which are embedded crystals of calcium carbonate called otoconia. The otoconia make the otolithic membrane heavier than the structures and fluids surrounding it; thus, when the head tilts, gravity causes the membrane to shift relative to the macula. The resulting shearing motion between the otolithic membrane and the macula displaces the hair bundles, which are embedded in the lower, gelatinous surface of the membrane. The vestibular system is a critical part of the inner ear that helps maintain balance, posture, and spatial orientation by detecting changes in motion and head position. It interacts with multiple neural pathways to ensure coordination of movement and stability. 1. Components of the Vestibular System The vestibular system is located in the inner ear and comprises the following main structures: a. Semicircular Canals Detect angular acceleration (rotational movements).  There are three canals: anterior, posterior, and lateral, each oriented in different planes. Contain a structure called the ampulla, which houses sensory hair cells embedded in a gelatinous structure called the cupula. Movement of endolymph (fluid) within the canals displaces the cupula, leading to activation of hair cells. b. Otolith Organs Utricle and saccule detect linear acceleration and head position relative to gravity. Contain hair cells embedded in the otolithic membrane, which is weighted by otoconia (calcium carbonate crystals). Otoconia: o Tiny crystals that provide mass to the otolithic membrane, enhancing its sensitivity to gravity and linear motion. o Displacement of the otoconia causes the otolithic membrane to slide, bending the stereocilia on the hair cells and initiating a neural signal. Movement causes shearing of the otolithic membrane, bending the stereocilia of hair cells. 2. Sensory Mechanisms a. Vestibular Hair Cells Key sensory receptors found in the semicircular canals and otolith organs. Each hair cell has stereocilia and a single kinocilium. o Bending of stereocilia towards the kinocilium leads to depolarization (excitation). o Bending away from the kinocilium causes hyperpolarization (inhibition). The sensitivity of hair cells depends on the structure they are in: o Ampullary hair cells in semicircular canals detect angular motion. o Macular hair cells in otolith organs detect linear motion and gravity. b. Endolymph and Perilymph Endolymph: High in potassium (K+), surrounds hair cells’ stereocilia. Perilymph: Similar to extracellular fluid, surrounds the base of the hair cells. Ionic differences drive mechanoelectrical transduction, allowing hair cells to generate electrical signals. In the semicircular canals, endolymph movement relative to head motion creates a deflection of the cupula.  In the otolith organs, shifts in the otolithic membrane due to gravity or linear acceleration stimulate hair cells. 3. Functions of the Vestibular System a. Balance and Posture Detects changes in head motion and position, sending signals to the spinal cord to adjust posture and maintain equilibrium. b. Vestibulo-Ocular Reflex (VOR) Stabilizes vision by coordinating eye movements with head movements. Example: When the head turns to the right, the eyes move left to maintain focus. c. Spatial Orientation Provides awareness of body position and motion in space. Integrates with the visual and somatosensory systems to create a sense of spatial orientation. 4. Central Pathways and Connections a. Vestibular Nerve and Nuclei Hair cells transmit signals via the vestibular nerve (part of cranial nerve VIII) to the brainstem’s vestibular nuclei. Vestibular nuclei integrate inputs and send outputs to: o Spinal cord: For postural adjustments. o Cranial nerve nuclei: Controls eye movements (e.g., VOR). o Cortex: Provides conscious perception of motion and balance. o Autonomic nervous system: Can trigger nausea and other responses. o Formatio reticularis: postural memory o Cortex: motion awareness Semicircular Canals: Structure and Function 1. Orientation: o The three semicircular canals (anterior, posterior, and lateral) are arranged orthogonally to each other. This configuration allows the system to detect rotational movement in all three dimensions. 2. Key Structures:  o Ampulla: An enlarged area at the base of each canal, housing the crista ampullaris, which contains sensory hair cells. o Cupula: A gelatinous structure that sits on top of the crista and encases the hair cell stereocilia. o Endolymph: A high-potassium fluid within the canals that moves in response to head rotation. Mechanism of Action 1. At Rest (No Motion): o When the head is stationary, the endolymph within the canals is also at rest. The cupula remains upright, and the hair cells are not significantly stimulated, resulting in baseline firing of vestibular nerve fibers. 2. During Rotation (Direction of Movement): o When the head rotates, inertia causes the endolymph to lag behind the bony canal's motion due to its viscosity. o This relative movement of endolymph displaces the cupula, bending the stereocilia of the hair cells. 3. Deflection of Hair Cells: o Deflection toward the kinocilium: Leads to depolarization of the hair cell, increasing neurotransmitter release and firing rate of the associated vestibular nerve fibers. o Deflection away from the kinocilium: Causes hyperpolarization, reducing neurotransmitter release and decreasing firing rate. Endolymph Flow and Inertial Forces - The flow of endolymph is opposite to the direction of head rotation, creating the necessary force to displace the cupula. - The extent of hair cell activation correlates with the speed and direction of head movement. Signal Processing 1. Neural Transmission: o Hair cells transmit signals to the vestibular nerve, which sends information to the brainstem's vestibular nuclei. o Signals are integrated with visual and somatosensory inputs to create a cohesive sense of balance and orientation. 2. Vestibulo-Ocular Reflex (VOR):  o Ensures stabilization of gaze during head movements by generating compensatory eye movements in the opposite direction of head rotation. Sensory systems Three categories of sensory information: Exteroception: registering information from outside of the body Interoception: registering information from inside of the body Proprioception: registration information about ourselves. The signals will only be send if they surpass a stimulus, which will help to filter unimportant details. Weber’s Law states that the radio of the increment threshold to the background intensity is constant (you will notice if you first grab 1 kg and after 1.2, but you won’t notice the difference between 10 and 10.2 kilos). This relationship is logarithmic. The equation is P = Kia We have specific receptors for different ranges (each receptor will respond to a different sensos, and the extremes will have bigger thresholds). By seeing which ones where activated, the brain can analyze and see for example, the temperature we are at. Types of receptors: Mechanoreceptors: Chemoreceptors: Photoreceptors: Thermoreceptors: We have slowly adapting receptors (SA), which maintain their activity as long as the stimulus is applied with minimal decline in firing rate (Tonic activity that is meant to provide continuous information to the brain), and rapidly adapting receptors (RA) that respond only at the onset (an possibly as well the offset) of the stimulus. Receptive fields will bring resolution and lateral inhibition contrast. Small receptive fields (e.g., in fingertips): High resolution, enabling fine detail detection. Small receptive fields (e.g., in fingertips): High resolution, enabling fine detail detection. Lateral Inhibition: A neural mechanism where activated sensory neurons inhibit the activity of neighboring neurons. Quality of the stimulus: frequency code gives intensity, temporal code gives duration. How does the brain know what signal it was? Labeled line: type of stimuli, location of stimuli. Each neuron is "labeled" to respond to a specific type of stimulus and carries that specific information to the brain. For example, in taste, certain neurons might be dedicated to salty, sweet, or bitter stimuli.  Population coding: the combined signal from many neurons encode the message. Smell- a single receptor can be activated by several molecules a combination of receptors (neurons) can decode the specific smell. Each neuron is "labeled" to respond to a specific type of stimulus and carries that specific information to the brain. For example, in taste, certain neurons might be dedicated to salty, sweet, or bitter stimuli. The role of the thalamus in sensory system The thalamus is a critical relay center in the sensory system. It processes and transmits sensory information from the periphery to the cerebral cortex. Key roles include: Relay Station: Directs sensory input (except olfaction) to the appropriate cortical regions for interpretation. Filtering: Screens sensory signals to emphasize relevant stimuli and suppress background noise. Integration: Combines inputs from multiple sensory modalities for a unified perception. Modulation: Regulates sensory signals through feedback from the cortex, affecting perception. Conscious Awareness: Plays a role in maintaining awareness of sensory experiences. Somatosensory Processing: Handles touch, pressure, pain, and temperature signals. Visual Pathway: Relays visual information via the lateral geniculate nucleus. Auditory Pathway: Relays sound signals through the medial geniculate nucleus. Motor-Sensory Interaction: Integrates sensory input with motor commands. Sleep-Wake Cycles: Influences sensory input processing based on alertness. This coordination ensures efficient sensory perception and response.  Touch, temperature and proprioception Low threshold, which detects normal touch Slowly adapting o Merkel: shape and texture perception, has the smallest receptive area and low frequency range o Ruffini: detects tangential force, hand shape, motion direction, with a big receptive area. Unknown frequencies. Rapidly adapting o Meissner: detects grip control, small receptive area, a low frequency range o Pacininan: detects distant events through transmitted vibration, entire finger, and big and high frequency range. High threshold, detects pain: free nerve endings. All of these mechanoreceptors will convert the mechanic stimuli into action potentials. Piezo channels They are mechanosensitive ion channels essentials for converting mechanical stimuli into electrical signals Piezo2 is located mainly in the nervous system including sensory neurons and brain areas. Piezo1 found in non-neuronal tissues throughout the body (regulates mechanotransduction in the cardiovascular system and respiratory, cell volume and blood flow. Accurate two-point discrimination requires a pattern where: Point 1: Activates a receptive field (sensory neuron) through contact. Point 2 (in between): Falls outside receptive fields, where no neurons are activated. Point 3: Activates another distinct receptive field. It depends in the receptive field size, the density, and the lateral inhibition. The two point discrimination threshold varies over the body. Proprioception Detects the state of our muscles and joints and it is very important for postural reflexes. It maintains the length of the muscle. Golgi tendon organ: detects muscle force, important for fine tuning muscle force, hypothesized to play a role in protective reflexes. The signals from proprioception will go to a large extent to the cerebellum. One neuron can signal to multiple locations What happens after activation? - Red: Dorsal column-medial lemniscus pathway: transmits signals related to fine touch, vibration. It can take information from both lower and upper body. 1. First-order neurons: Travel via the dorsal columns of the spinal cord. Enters the spinal cord via the dorsal root and ascends in the dorsal columns. The cell body is located in the dorsal root ganglion.  Fasciculus gracilis: Carries input from the lower body. Fasciculus cuneatus: Carries input from the upper body. Terminates in the nucleus cuneatus (upper body) or nucleus gracilis (lower body) in the medulla oblongata. 2. Second-order neurons: Synapse in the nucleus gracilis and nucleus cuneatus in the medulla oblongata. Cross to the opposite side (decussate). Ascend as the medial lemniscus to the ventral posterior lateral (VPL) nucleus of the thalamus. 3. Third-order neurons: Projects sensory information from the thalamus to the primary sensory cortex (postcentral gyrus). - Blue: Spinothalamic tract- anterolateral system. The spinothalamic tract, part of the anterolateral system (ALS), transmits sensory information about pain, temperature, and crude touch to the brain. 1. First-Order Neurons (Peripheral Nerves to Spinal Cord): Signals travel along the axons of first- order neurons, entering the spinal cord via the dorsal root (cell body in the DRG). First-order neurons synapse with second-order neurons in the dorsal horn of the spinal cord. 2. Second-Order Neurons (Spinal Cord to Thalamus). Axons of second-order neurons cross to the contralateral side of the spinal cord. After crossing, they ascend through the anterolateral column to the thalamus. The lateral spinothalamic tract carries pain and temperature. The anterior spinothalamic tract carries crude touch and pressure. Second-order neurons terminate in the ventral posterior nucleus (VPN) of the thalamus. 3. Third-Order Neurons (Thalamus to Cortex): they project from the thalamus through the internal capsule to the primary somatosensory cortex in the postcentral gyrus. It is important to note that not all axons in the spinal nerve alike, they have different diameter and myelination will give different speed.  Postcentral gyrus: Primary somatosensory cortex. Here the signal has reached consciousness, and there is a clear division into body parts. The area of the cortex correlates with sensory ability We have four parts corresponding with different locations, and within each area there is further specialization. - 3a handles proprioception - 3b handles tactile information - 1 starts to interpret texture of objects - 2 decodes shape and size - Somatosensory cortex, determines what type of object - Parietal areas determine how to interact with the object. - Amygdala and hippocampus, this last one for long-term memory. - Motor and premotor cortical areas: detailed understanding of the object. The cortical areas are not fixed in size but can change depending on use. Physiology of pain Pain is an unpleasant sensory and emotional experience associated with actual and potential tissue damage, described in terms of such damage. This needs to reach the brain for a person to be aware of the pain. A painful stimulus is also called a noxious stimulus. Types of pain: - First pain: brief, priarp and well localized - Second pain: longer-lasting, burning and less well localized. Types of noxious stimuli: - Mechanical - Chemical - Thermal Sensory receptors for pain are called nociceptors and are free nerve endings. They are peripheral afferent neurons that are sensitive to injuries or pain, normally caused by extreme thermal exposures, mechanical forces or other noxious stimuli. Different types - Ad fibers: myelinated and fast, correspond to first pain - C fibers: unmyelinated, slow and second pain. - Common features: relatively sow when compared to other neurons, relay pain information, originate in the DRGM, Pseudounipolar neurons. At peripheral nerve terminals there are different transducer channels that signal for different stimuli, like piezo2 which signals for mechanical pain; TRPV receptors, that signal for cold and heat, and ASIC that signals for chemical stimuli (low pH). In the DRG they have the cell body and then they go to the CN where they use glutamate to send information to a second order neuron. These receptors signal through the anterolateral tract. A dermatome is an area of skin that is served by a single spinal nerve. The dermatomes are the same for noxious stimuli and innocious stimuli. Types of pain - Nociceptive pain: pain that arises from actual or threatened damage to non-neuronal tissue and is due to the activation of nociceptors. - Neuropathic pain: caused by a lesion or disease of the somatosensory nervous system. - Referred pain: pain that arises from damage to visceral organs but it is misperceived as coming from a somatic location. This is because some 2nd order neurons receive converging input from nociceptive and non-nociceptive afferents (wide-dynamic range neurons) and some of these receive visceral sensory information. Thus, pain due to damage to some visceral organs may be misperceived as pain coming from a somatic location. Aspects of pain - Discriminative aspect: relates to the sensory qualities of pain. This is intensity, location and quality. - Affective, motivational and cognitive. Modulation of pain - Gate control theory: By activating non-nociceptive mechanoreceptors, signals coming from nociceptive c-fibers can be inhibited. This theory helps explain why certain actions, such as rubbing an injury or applying pressure, can reduce the perception of pain. - Descending pathways: production of endogenous opioids that mainly reduce pain (enkephalins, dynorphins and endorphins) and these inhibit ascending nociceptive signaling. - Sensitization - Central: increased responsiveness of nociceptive neurons in the central nervous system to their normal afferent input. Mechanism: ▪ Windup: progressive increase in the discharge rate in response to repeated low frequency activations. ▪ Activation of voltage-dependent L-type calcium channels ▪ LTP-like enhancement of pos-synaptic potentials. - Peripheral: increased responsiveness and reduced threshold of nociceptive neurons in the periphery to the stimulation of their receptive fields. An ”inflammatory soup” with metabolites from inflammatory cells as well as nociceptors potentiate the response of transducer channels. These all can cause:  - Hyperalgesia: increased pain - Allodynia: pain evoked by stimuli that is usually not painful. - Analgetic drugs Vision In the first picture we represent the external muscles involved in the moving of the eye. - The layer topping the cornea is the conjunctiva. - Sclera and cornea are made of the same thing but the collagen structure is different. Sclera is random and cornea is latticed. - Retina: where photo transduction happens. - Corpus vitreum: gelatinous ball. - Iris: has the muscles that help regulate the size and does not let light pass through. - Lens: also regulates size to help with focusing. Changes focal point with the help of the ciliary muscle. - M. sphincter pupillae: contracts when there is too much light. - M. dilatator pupillae: widens it where there is too low light and contracts. These two muscles are affected by the para and sympathetic system (drugs). When the ciliary muscle contracts the zonule fiber also does this and the eye becomes rounder and smaller. With age, you lose elasticity here. - Excavatio disci refers to a blind spot that has no photoreceptors but the brain fills that blank spot. - Retinal pigment epithelium: maintain a favorable local environment for the photoreceptors. They are active in the recycling of the disks are the molecules necessary for phototransduction. - Rods have their disks inside the cell and in cones it is part of the cellular membrane. Phototransduction From electromagnetic energy to action potential. Unlike others stimuli, it is hyperpolarization the response to the stimuli.  1. Light activates rhodopsin in the membrane disks by turning 11-cis retinal into all-trans retinal 2. This will activate transducing 3. Its alpha part will activate a phosphodiesterase 4. It moves to the cell membrane and converts cGMP to GMP 5. The channels close without cyclic GMP 6. Hyperpolarization  Light adaptation and regulation Ca²⁺ has an inhibitory effect on guanylate cyclase, which synthesizes cyclic GMP (cGMP). A decrease in Ca²⁺ (due to ion flow changes triggered by light) relieves this inhibition. With less Ca²⁺, guanylate cyclase activity increases, producing more cGMP, leading to a higher threshold for light sensitivity. This feedback loop increases the threshold for light sensitivity, making the photoreceptor less responsive to continued or excessive light exposure (a phenomenon called light adaptation).  Retinoid cycle Regenerates 11-cis-retinal. 1. All-trans-retinol is transported from photoreceptors to the RPE by interphotoreceptor retinoid-binding protein (IRBP). 2. In the RPE, all-trans-retinol undergoes a series of enzymatic steps 3. 11-cis-retinal is transported back to photoreceptor cells by IRBP, where it re-binds to opsin, forming rhodopsin, ready for the next cycle. The color does not disappear in the dark but the cones are not activated. Another thing to notice is that cones synapse to one bipolar cell while many rods synapse to one bipolar cells. The central processing of the input from different ganglion cells (cones) relates to the fact that the cones have different types of axons and respond to specific stimuli. The brain will see which ones are activated. If you miss one cone type you have color blindness.  Contrast To perceive the objects we differentiate them with the background by the edges. This process starts in the retina. We first the edges then the constituents and then composition and the surroundings. How do we search for the edges? For this, two types of ganglion cells are essential: on-center and off-center ganglion cells. Every ganglion cell in the retina has a receptive field, which is the area of the retina where light stimuli influence its activity. Divided in center and surround. - On-center ganglion: excited by light in the center of their receptive field and inhibited by light in the surrounding area. They will depolarize when light strikes the center and the surround is dark. - Off-center: inhibited by light in the center of their receptive field and excited by light in the surrounding area. Depolarize when the center is dark and the surround is illuminated. - Center: The central portion of the receptive field, directly connected to the ganglion cell via bipolar cells. - Surround: The surrounding area of the receptive field, indirectly connected to the ganglion cell via horizontal cells.  Central visual processing - Visual cortices – the road to V1 (primary visual cortex). Ocular dominance: both eyes send signals to both parts pf the brain. Ocular dominance regions refer to places where images from the two eyes are united. Orientation specificity refers to the ability of certain neurons in V1 to respond maximally to edges, bars, or lines of a specific orientation. Travelling: 1. Retina: Initial Light Detection. Photoreceptors (rods and cones) Signals pass through: o Bipolar cells: Transmit signals from photoreceptors to ganglion cells. o Ganglion cells: Process information and generate action potentials.  Axons of ganglion cells form the optic nerve. 2. Optic Nerve and Optic Chiasm. The optic nerve carries visual information from each eye. At the optic chiasm: fibers from the nasal retina of each eye cross to the opposite hemisphere. Left visual field → Right hemisphere. Right visual field → Left hemisphere. 3. Lateral Geniculate Nucleus (LGN) in the Thalamus. LGN neurons preserve the spatial organization (retinotopy) of the visual field. 4. Optic Radiations. From the LGN, visual signals travel via the optic radiations: Meyer's Loop: Carries signals from the upper visual field (lower retina) to the temporal lobe. Parietal Pathway: Carries signals from the lower visual field (upper retina). Both pathways converge in the primary visual cortex (V1). 5. Primary Visual Cortex (V1). Located in the occipital lobe. Processes: Orientation specificity: Detects edges, lines, and orientations. Retinotopy: Preserves spatial mapping of the visual field. Simple and complex cells: Integrate input for basic shape detection. 6. Beyond V1: Visual Processing Streams. After initial processing in V1, visual information splits into two streams: - Dorsal Stream ("Where" Pathway). Travels to the parietal lobe. Processes: o Spatial relationships. o Motion. o Object locations. Helps with navigation and interaction with objects. - Ventral Stream ("What" Pathway). Travels to the temporal lobe.Processes: o Object recognition. o Color and texture. o Fine details. Crucial for identifying faces and objects.  - Ciliary ganglion – the pupillary reflex. Symmetrical - shining the light into one eye causes the pupils in both eyes to contract - The hypothalamus – regulating the circadian reflex. Some ganglion cells have their own opsin ’melanopsin’. They’re called intrinsically photosensitive retinal ganglion cells (ipRGC). ipRGCs send signals directly to the suprachiasmatic nucleus (SCN) in the hypothalamus. This helps the SCN synchronize the internal biological clock with the external environment. - The superior colliculus – shifting gaze. Connect to the nuclei for Cranial nerve 3,4 and 6, controlling the extra-ocular muscles. Saccades are fast gaze shifting movements originating from the superior colliculus The chemical senses The olfactory (threshold 0.01 nM) and gustatory system (0.1 μM) threshold react to molecules in the environment and trigger neural activity giving rise to perceptual experiences. Stimulation can come from the olfactory cilia and the soma. When you stimulate the cilia you get a bigger depolarization. An odorant molecule will bind to a receptor protein activating the active G-protein Golf that using GTP will activate adenylyl cyclase III converting ATP into cAMP that will then activate Na+ Ca2+ cAMP-gated channel, calcium ions passing by and activating a calcium ion Cl- channel, sodium leaving the cell and sodium calcium exchanger, increasing the concentration of sodium. Each ORN (olfactory receptor neuron) expresses one type of odorant receptor. The ORNs are organized and segregated both in the olfactory epithelium and the glomeruli. Each odorant responds to multiple odorants and each odorant activates multiple ORNs. It is likely the pattern of activation that gives rise to the perception of a specific smell. It is usual for what we recognize as specific smells to be made up diverse and multiple odorants. We can increase our ability to track smells and with age we lose this. Temporal lobe. The vomeronasal system states that there are pheromones (same species) and kairomones (different species). No evidence in humans although some indication of pheromonal behavioral and physiological changes exist. Gustation - Salt uses a sodium channel - Acids (sour): uses a channel for protons - Sweet, umami, bitter: GPCR that then opens calcium channels. Different savors are not located evenly and they are found everywhere, however, at different densities which is why we use the savor maps.