Difficulty: Intermediate to Advanced | Prerequisites: Neurophysiology notes (membrane potential, action potentials, graded potentials, synaptic transmission), G-protein signalling basics
This block picks up from synaptic transmission and covers two things: the diversity of neurotransmitters and their receptors, and then the full sweep of sensory systems, from how stimuli are detected to how the nervous system encodes their identity, location, intensity and duration. You will move through chemoreception (smell and taste), mechanoreception (touch, proprioception, hearing, balance) and photoreception (vision). The common thread is that every sensory system converts a physical or chemical stimulus into changes in membrane potential and, eventually, patterns of action potentials. If you understand graded potentials, G-protein signalling and action potential frequency coding from the previous lectures, you have the foundation.
Neurotransmitters act through ionotropic (direct channel) or metabotropic (GPCR-mediated) receptors, and the same NT can be excitatory or inhibitory depending on the receptor. Sensory systems encode four features of a stimulus: modality (what), location (where), intensity (how strong) and duration (how long). Chemoreception, mechanoreception and photoreception each use specialised receptor proteins and transduction pathways, but all ultimately convert stimuli into membrane potential changes and action potential patterns.
Ionotropic receptor
A receptor where the neurotransmitter binds directly to an ion channel, opening it. Fast response. Think of it as a direct gate: NT arrives, channel opens, ions cross.
Metabotropic receptor (GPCR)
A receptor where NT binding triggers a G-protein signalling cascade that eventually opens ion channels or modifies gene expression. Slower but more versatile. The ion channel is activated by the signalling pathway, not directly by the NT.
Generator potential
A graded potential that occurs directly in a sensory neuron as a result of the stimulus. The receptor is part of the dendrite of the afferent neuron itself.
Receptor potential
A graded potential that occurs in a separate receptor (accessory) cell, which then transmits the signal to the sensory neuron. The receptor cell is not the afferent neuron.
Dynamic range
The range of stimulus intensities over which a receptor exhibits changing responses, from threshold (weakest detectable stimulus) to saturation (maximal response).
Range fractionation
Different receptors cover different parts of the stimulus intensity spectrum. This expands the total range and improves discrimination.
Receptive field
The region of the sensory surface that produces a response when stimulated. Smaller receptive fields allow greater spatial acuity (finer detail).
Lateral inhibition
Signals from neurons at the centre of a receptive field inhibit surrounding neurons, enhancing contrast, decreasing noise and improving edge detection.
Tonic receptor
A receptor that maintains a sustained response to a continued stimulus.
Phasic receptor
A receptor that responds to changes in stimulus intensity but adapts (decreases firing rate) if the stimulus remains constant.
Odorant receptor neuron (ORN)
A bipolar neuron in the olfactory epithelium that expresses a single type of GPCR odorant receptor. Each receptor can recognise more than one odorant, and each odorant can stimulate more than one receptor type.
Hair cell
A mechanosensory accessory cell used for hearing and balance. Bathed in endolymph (high K+ outside the cell). Movement of stereocilia opens mechanically gated cation channels (TMC1/2), causing depolarisation.
Rods
Ciliary photoreceptors sensitive to very dim light. Rod-shaped outer segment. Many rods converge onto a single bipolar cell, giving a large receptive field but low spatial acuity.
Cones
Ciliary photoreceptors sensitive to brighter light and responsible for colour detection. Cone-shaped outer segment. In the fovea, single cones connect to single bipolar cells, giving high spatial acuity.
Fovea centralis
A specialised region of the retina containing exclusively cones, devoid of capillaries and with displaced obstructing cell layers. Provides the sharpest central vision.
More than 50 neurotransmitter substances are known, falling into categories: amino acids, neuropeptides, biogenic amines, acetylcholine and miscellaneous (gases, purines). A single neuron can produce and release more than one NT.
The same neurotransmitter can have opposite effects on different target cells depending on the receptor it binds. Glutamate, for example, can be excitatory or inhibitory.
Ionotropic receptors:
NT binds directly to the receptor/channel
Ions cross the membrane
Rapid change in membrane potential
Example: GABA-A receptor is an ionotropic Cl- channel (inhibitory).
Metabotropic receptors (GPCRs):
NT binds to the receptor
G-protein signalling cascade is activated
Ion channels are opened indirectly, or existing proteins are modified, or gene expression changes
Slower, more coordinated cellular response
Example: GABA-B receptor is metabotropic.
Putting it all together (signal flow in a neuron):
RMP is set by Na+ and K+ leak channels and the Na+/K+ pump (K+ contributes most)
Ligand-gated channels and metabotropic receptors produce graded potentials (PSPs)
Axon hillock integrates signals; if threshold is reached, an AP is initiated (dense population of voltage-gated Na+ and K+ channels)
AP propagates to the axon terminal
Voltage-gated Ca2+ channels open at the terminal, driving NT release via exocytosis
Ca2+ pump restores the calcium gradient after release
Receptor classification by stimulus modality:
Chemoreceptors: detect chemicals
Mechanoreceptors: detect pressure and movement (including proprioception)
Photoreceptors: detect light
Thermoreceptors: detect temperature
Electroreceptors: detect electric fields
Magnetoreceptors: detect magnetic fields (to our knowledge, humans lack these)
Sensory receptors encode four features:
Stimulus modality (what type of stimulus): encoded by labelled pathways. Perception is based on the pathway activated, not the stimulus identity. This is why pressing on closed eyes produces the sensation of light: photoreceptor pathways are activated by pressure, and the visual cortex interprets any signal on that pathway as light.
Stimulus location (where): encoded by receptive fields. Smaller receptive fields = greater spatial acuity. Hands have smaller receptive fields than the back, which is why you can distinguish two points of contact on your fingertips but not on your upper back.
Stimulus intensity (how strong): encoded by action potential frequency. Stronger stimulus = higher AP frequency. Related concepts:
Dynamic range: from threshold to saturation
Large dynamic range = poor discrimination (large stimulus change needed for a small change in AP frequency)
Narrow dynamic range = good discrimination (small stimulus change produces a noticeable change in AP frequency)
Range fractionation: different receptors handle different parts of the intensity spectrum, expanding range and improving discrimination
Logarithmic encoding: allows increased dynamic range without completely sacrificing discrimination. Light and sound are encoded logarithmically.
Stimulus duration (how long): encoded by tonic vs phasic receptors
Tonic: sustained response to continued stimulation
Phasic: respond to changes but adapt if stimulus is constant
Lateral inhibition further improves acuity by enhancing contrast, decreasing noise and improving edge/boundary detection.
Vertebrate olfaction (smell):
Olfactory epithelium sits in the roof of the nasal cavity, covered by a mucus layer. Water-soluble molecules dissolve easily; lipophilic odorants need odorant binding proteins to dissolve in the mucus.
Odorant receptor neurons (ORNs) are bipolar neurons with ciliated dendrites that express GPCRs.
Olfactory transduction pathway:
Odorant binds to its receptor, causing a conformational change
Activated G protein (Golf) activates adenylate cyclase
Adenylate cyclase converts ATP to cAMP
cAMP opens cAMP-gated non-selective cation channels
Ca2+ and Na+ enter the cell, producing a generator potential
Ca2+ opens Ca2+-activated Cl- channels; Cl- leaves the cell, increasing depolarisation
Generator potential opens voltage-gated Na+ channels, triggering APs
Odorant receptor logic:
Each olfactory neuron expresses only one odorant receptor protein
Each receptor can recognise more than one odorant
Each odorant can stimulate more than one receptor type
Every perceivable odour activates a unique combination of odorant GPCRs (combinatorial code)
Afferent ORNs with the same GPCR connect to the same glomerulus in the olfactory bulb
Vertebrate gustation (taste):
Taste receptor cells (TRCs) are neuroepithelial cells clustered in taste buds. Signals are transmitted to primary afferent neurons.
Salty and sour (direct ion channels):
Salty: Na+ enters TRC through Na+ channels, depolarisation opens voltage-gated Ca2+ channels, Ca2+ influx triggers serotonin (5-HT) release
Sour: H+ ions activate Otop1 channels, protons enter and lower pH, low pH activates Na+ channels, depolarisation follows the same Ca2+ pathway
Sweet, umami and bitter (GPCR-mediated):
Tastant binds GPCR, causing conformational change
Activated G protein activates phospholipase C (PLC)
PLC converts PIP2 to IP3
IP3 releases Ca2+ from intracellular stores
Ca2+ activates TRPM channels (non-selective), Na+ enters
Depolarisation opens voltage-gated CALHM1/3 channels
ATP is released as the neurotransmitter, binding P2X receptors on the afferent neuron
Invertebrate chemoreception:
Insects use sensilla (hair-like projections). Sensory neuron dendrites project into sensilla, and odorants/tastants enter through pores. GPCR-like proteins localise to the dendrites. These are also used for pheromone detection and mechanosensation.
Mechanoreceptors couple mechanical stimuli to ion channels, primarily ENaC (Na+ channel, causing depolarisation) and TRP channels (non-selective cation channels).
Touch receptors in the skin:
Merkel's discs: respond to light pressure, tonic (sustained response)
Pacinian corpuscle: responds to deep pressure, phasic (responds to onset/offset of pressure)
Ruffini corpuscles: tonic, respond to sustained pressure/vibration
Proprioceptors:
Monitor body position in space
Spindle fibres: detect stretch of muscles
Golgi tendon organs: detect stretch of tendons
Sensory nerve endings wrap around muscle fibres and detect stretch
Hair cells (hearing and balance):
Accessory cells that transmit signals to afferent neurons
Bathed in endolymph, which has high K+ relative to the cell (opposite of typical, where K+ is higher inside)
Movement of stereocilia opens mechanically gated cation channels (TMC1/2)
Because [K+] is higher outside, K+ flows into the hair cell when channels open, causing depolarisation (the opposite of what happens in a typical neuron)
Hair cells maintain baseline neurotransmitter release even without deflection (baseline activity)
Deflection towards the longest stereocilium: more channels open, more depolarisation, more NT release, higher AP frequency
Deflection away from the longest stereocilium: channels close, hyperpolarisation, decreased NT release, lower AP frequency
The vestibular apparatus uses hair cells to detect head position and movement.
Maculae of the utricle and saccule:
Detect linear acceleration and tilting
Hair cell stereocilia are embedded in a gelatinous matrix topped with otoliths (small calcium carbonate stones)
Movement of the head shifts the otoliths, which moves the gelatinous matrix, which deflects the stereocilia
Forward acceleration: otoliths lag behind, deflecting stereocilia in one direction (increased AP firing)
Backward acceleration: stereocilia deflect the opposite way (decreased AP firing)
Cristae of the semicircular canals:
Detect angular (rotational) acceleration
Fluid (endolymph) moves the cupula, which deflects stereocilia in the hair cells
Excitation vs inhibition depends on the direction of movement and the location of the hair cells
Three semicircular canals are oriented in different planes, covering rotation in all directions
Middle ear:
Vibration of the tympanic membrane (eardrum) is transferred to three small bones (ossicles):
Malleus (hammer)
Incus (anvil)
Stapes (stirrup)
The ossicles amplify the vibration and transfer it to the oval window, which connects to the inner ear (cochlea).
Cochlea:
A coiled tube leading from the oval window around to the round window
Upper vestibular duct and lower tympanic duct are filled with perilymph
Between them sits the cochlear duct, which contains the organ of Corti on the basilar membrane
Incoming sounds cause the oval window to vibrate, creating waves in the fluid that deflect the basilar membrane, moving stereocilia in hair cells
Organ of Corti (two hair cell types):
Inner hair cells (sound detection and transduction):
Primarily responsible for detecting sound
Louder sounds cause greater basilar membrane movement, greater depolarisation of the hair cell, more APs in the afferent neuron
Release glutamate as a neurotransmitter
Movement of stereocilia towards the longest stereocilium = excitation
Outer hair cells (amplification):
Critical for amplifying sound
Change shape in response to sound waves (somatic electromotility, or "dancing")
Stereocilia move in response to sound, mechanosensory channels open, K+ enters (depolarisation), depolarisation activates a voltage-sensitive motor protein (prestin), which changes the cell's shape and pulls on the basilar membrane
This increases the amount of basilar membrane that moves in response to stimuli (amplification)
Unlike inner hair cells, their primary role is amplification rather than NT release
Hair cells are located along the entire length of the basilar membrane. Both types detect basilar membrane movements, but they serve different functions.
Photoreceptive opsins:
7-transmembrane-spanning GPCRs localised to membranes in the outer segments of vertebrate photoreceptors
Use vitamin A-derived chromophores as cofactors
Photons cause isomerisation of the chromophore (cis to trans)
This triggers a conformational change in the opsin and dissociation of the chromophore ("bleaching")
G-protein signalling events then cause changes in membrane potential
Two classes of photoreceptor across the animal kingdom:
Rhabdomeric photoreceptors: signal through Gq. Light triggers PLC activation, PIP2 is converted to DAG and IP3, DAG activates TRP cation channels, Ca2+ and Na+ enter the cell, depolarising it. Recently discovered in vertebrates too, where they help entrain internal clocks to light/dark cycles.
Ciliary photoreceptors: signal through Gi/transducin. Light activates transducin, which activates PDE, converting cGMP to GMP. Decreased cGMP closes Na+ channels, hyperpolarising the cell. This is the type found in mammalian rods and cones.
Mammalian eye anatomy:
Muscle fibres of the iris change pupil diameter, controlling light entry
Cornea: refracts light and does most of the focusing
Lens: fine-tunes focus onto the retina by changing shape (accommodation). Ciliary muscle contracts, ligaments slacken, lens bulges for nearby objects.
Choroid: pigmented layer that absorbs light. In nocturnal animals it contains the tapetum lucidum (reflective layer that makes eyes "glow")
Rods vs cones:
Rods: sensitive to very dim light. Rod-shaped outer segment. Many rods synapse onto a single bipolar cell (convergence), giving large receptive fields but low spatial acuity. More abundant in nocturnal animals.
Cones: require higher intensity (more photons). Cone-shaped outer segment. In the fovea, one cone connects to one bipolar cell, giving small receptive fields and high spatial acuity. Responsible for colour vision.
Vision uses logarithmic encoding of stimulus intensity.
Fovea centralis:
Exclusively cones (acuity)
Devoid of capillaries (less refraction of light)
Obstructing cell layers are displaced to the side
Provides the sharpest, most accurate central vision
Optic disc (blind spot): where ganglion cell axons exit the retina to form the optic nerve. Contains no photoreceptors.
Colour discrimination:
Based on the absorbance spectra of different cone types (short, medium, long wavelength)
Splitting stimulus intensities among different receptors covers a larger dynamic range
Red-green colour blindness: loss of red or green cones (most common type)
Blue-yellow colour blindness: loss of blue cones (less common)
Retinal ganglion cell receptive fields:
Ganglion cells have centre-surround receptive fields that enhance borders and contrast.
Condition | ON-centre ganglion cell | OFF-centre ganglion cell |
|---|---|---|
Centre illuminated only | Increases APs | Decreases APs |
Surround illuminated only | Decreases APs | Increases APs |
Diffuse illumination (both) | Weak response | Weak response |
Lateral inhibition in the retina:
Horizontal cells: function at the photoreceptor and bipolar cell level
Amacrine cells: function at the bipolar and ganglion cell level
Neural circuitry of retinal processing (simplified):
Light hyperpolarises the photoreceptor, reducing transmitter release
A decrease in inhibitory signalling depolarises the bipolar cell
Depolarisation increases excitation of the ganglion cell
In reality, the circuitry is more complex, with many variations in connectivity patterns.
No new mathematical formulas are introduced in this unit. The key diagrams to know:
Olfactory transduction pathway: odorant > GPCR > Golf > adenylate cyclase > cAMP > cation channel > depolarisation
Taste transduction pathways: salty (Na+ direct entry), sour (H+ via Otop1), sweet/umami/bitter (GPCR > PLC > IP3 > Ca2+ release > TRPM > ATP release)
Hair cell mechanics: stereocilia deflection towards/away from tallest stereocilium, with K+ entry from endolymph
Cochlear cross-section: vestibular duct, cochlear duct (organ of Corti on basilar membrane), tympanic duct
Ciliary photoreceptor pathway: light > chromophore isomerisation > transducin (Gi) > PDE > cGMP drops > Na+ channels close > hyperpolarisation
ON-centre / OFF-centre receptive field diagram: centre vs surround illumination effects on ganglion cell firing
Retinal circuit: photoreceptor > bipolar cell > ganglion cell, with horizontal and amacrine cells providing lateral inhibition
Cochlear implants bypass damaged hair cells and directly stimulate the auditory nerve, which is why understanding the transduction role of inner hair cells matters clinically. Noise-induced hearing loss results from damage to outer hair cells (the amplifiers), which is why it often starts as difficulty hearing quiet sounds rather than total deafness. Colour blindness is directly explained by the loss of specific cone types covered in the colour discrimination section.
Students often think KV channels in hair cells cause hyperpolarisation like they do in neurons. In hair cells, K+ is higher outside the cell (in endolymph), so opening K+ channels causes K+ influx and depolarisation.
Students often assume that seeing light when you rub your eyes means the stimulus is light. It is pressure. The visual cortex interprets any activation of photoreceptor pathways as light, regardless of the actual stimulus.
Students sometimes confuse dynamic range with discrimination. A large dynamic range means the receptor covers a wide span of intensities, but it discriminates poorly between nearby intensities. A narrow dynamic range discriminates well but saturates quickly.
Students often think outer hair cells detect sound. Their primary role is amplification (somatic electromotility). Inner hair cells are the ones that transduce basilar membrane vibration into neural signals.
⚠️ Know the difference between ionotropic and metabotropic receptors and be able to classify examples (GABA-A = ionotropic, GABA-B = metabotropic). This was tested as an iClicker question.
⚠️ Understand that glutamate can be excitatory OR inhibitory depending on the receptor.
⚠️ Be able to explain the four features of stimulus encoding (modality, location, intensity, duration) with examples.
⚠️ The pressed-eye example (seeing light from pressure) illustrates labelled-line coding of stimulus modality. This was directly tested.
⚠️ Know the olfactory combinatorial code: one neuron = one receptor, but each receptor responds to multiple odorants and each odorant activates multiple receptors.
⚠️ Hair cell K+ entry causing depolarisation (opposite of typical neurons) is a favourite exam question.
⚠️ Know the difference between inner hair cells (detection/transduction) and outer hair cells (amplification).
⚠️ Understand ON-centre vs OFF-centre receptive fields in retinal ganglion cells.
⚠️ Know why rods have lower spatial acuity than cones (convergence, larger receptive fields) and why cones are predicted to be less abundant in nocturnal animals.
True or false: GABA-A is a metabotropic receptor. (False. GABA-A is ionotropic; GABA-B is metabotropic.)
Fill in the blank: The range of stimulus intensities over which a receptor exhibits changing responses is called the ______. (Dynamic range)
True or false: In hair cells of the inner ear, K+ entry causes hyperpolarisation. (False. K+ is higher in the endolymph than inside the hair cell, so K+ entry causes depolarisation.)
Fill in the blank: The type of photoreceptor that provides high spatial acuity and colour vision is the ______. (Cone)
True or false: A phasic receptor maintains a sustained response to a constant stimulus. (False. Phasic receptors adapt; tonic receptors sustain.)
Q: Which of the following receptors is most likely a chloride channel: AMPA, GABA-A, GABA-B, or dopamine receptor?
A: GABA-A. It is an ionotropic Cl- channel. Chloride entry hyperpolarises the cell, making GABA-A inhibitory. GABA-B is metabotropic and not a direct ion channel.
Q: You close your eyes and press gently on them, and you see flashes of light. Explain why.
A: Pressing activates photoreceptor pathways through mechanical stimulation (pressure, not light). The visual cortex is wired to interpret any signal arriving on photoreceptor pathways as light. Perception depends on the pathway activated, not the actual stimulus identity.
Q: Receptor A has a dynamic range of 50 to 500 units. Receptor B has a dynamic range of 200 to 300 units. Which would be better at discriminating between stimulus intensities of 220 and 250?
A: Receptor B. A narrower dynamic range means a given change in stimulus intensity produces a larger change in AP frequency, giving better discrimination within that range.
Q: What effect would you observe upon opening K+ channels in a hair cell bathed in endolymph?
A: K+ ions flow into the cell (because [K+] is higher in endolymph than inside the cell), and the membrane potential increases (depolarisation). This is the opposite of what happens in a typical neuron.
Q: Compare the roles of inner and outer hair cells in the organ of Corti.
A: Inner hair cells are primarily responsible for detecting sound: basilar membrane movement deflects their stereocilia, leading to depolarisation and glutamate release onto afferent neurons. Outer hair cells are primarily responsible for amplification: they change shape in response to sound waves (somatic electromotility via prestin), pulling on the basilar membrane to increase the area of movement.
Q: Why do rods provide lower spatial acuity than cones?
A: Many rods converge onto a single bipolar cell, and multiple bipolar cells converge onto a single ganglion cell. This gives rod pathways large receptive fields, which means the brain cannot pinpoint exactly which rod was stimulated. Cones in the fovea have a one-to-one-to-one connection (one cone, one bipolar cell, one ganglion cell), giving small receptive fields and high spatial acuity.
Q: Explain how lateral inhibition improves sensory acuity.
A: Neurons at the centre of a receptive field inhibit neurons in the surround. This enhances contrast at edges and boundaries, reduces noise and makes it easier to distinguish where one stimulus ends and another begins.
The G-protein signalling pathways here (Golf in olfaction, Gq in rhabdomeric photoreceptors, Gi/transducin in ciliary photoreceptors) are all variations on the GPCR signalling you covered in the endocrine and cell signalling units. The same second messengers (cAMP, IP3, DAG) reappear in different contexts.
Hair cell mechanics connect back to the membrane potential and ion gradient material from Lectures 13 to 16; the twist is that the K+ gradient is reversed in endolymph, which makes depolarisation work differently.
The receptive field and lateral inhibition concepts from vision apply broadly to somatosensory processing and will reappear if you study higher-level cortical processing.
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