Topic 8: Grey Matter — Edexcel A-Level Biology A (Salters-Nuffield)

Neurones are specialised cells that transmit electrical impulses. A sensory neurone carries impulses from receptors to the central nervous system; it has a cell body in a dorsal root ganglion, a long dendron and a short axon. A relay neurone lies entirely within the CNS, connecting sensory and motor pathways; it has many short dendrites and a short axon. A motor neurone carries impulses from the CNS to an effector such as a muscle or gland; it has a large cell body in the CNS, many dendrites and a long axon. Schwann cells wrap around axons, forming the myelin sheath. Myelination provides electrical insulation and allows saltatory conduction, where the impulse jumps between nodes of Ranvier, increasing speed. Schwann cells also play a crucial role in facilitating the regeneration and repair of damaged peripheral axons.

A stimulus is a detectable change; receptors transduce it into electrical activity in sensory neurones. Impulses travel to the CNS, where intermediate neurones integrate inputs, then motor neurones carry impulses to effectors — muscles or glands — which respond. In a simple reflex arc, the sensory neurone synapses with a relay neurone in the spinal cord, which synapses with a motor neurone; the response is rapid and involuntary. Pupil diameter illustrates this: in bright light, retinal photoreceptors signal the CNS, parasympathetic motor neurones cause the circular iris muscle to contract and the radial muscle to relax, so the pupil constricts. In dim light, sympathetic motor neurones cause radial muscles to contract and circular muscles to relax, dilating the pupil.

At rest, the axon membrane is polarised: the sodium–potassium pump moves 3 Na⁺ out for every 2 K⁺ in, and the membrane is more permeable to K⁺ than to Na⁺, so the inside is negative relative to the outside. A stimulus depolarises the membrane if it reaches threshold: voltage-gated Na⁺ channels open, Na⁺ enters, and the potential rises. Na⁺ channels then inactivate and voltage-gated K⁺ channels open, so K⁺ leaves and the membrane repolarises, briefly overshooting into hyperpolarisation before the resting potential is restored. The action potential travels along the axon. In myelinated axons, the myelin sheath insulates the membrane, so depolarisation occurs only at nodes of Ranvier; the impulse jumps from node to node in saltatory conduction, which is faster than continuous conduction in unmyelinated axons.

A synapse is a junction where a neurone meets another cell; the presynaptic knob holds vesicles of neurotransmitter, and the postsynaptic membrane carries receptors. Arrival of an action potential depolarises the presynaptic membrane, opening voltage-gated Ca²⁺ channels, so Ca²⁺ enters and vesicles fuse with the membrane, releasing neurotransmitter by exocytosis into the cleft. Acetylcholine diffuses across and binds complementary receptors on the postsynaptic membrane, opening cation channels; Na⁺ entry depolarises the cell, and if threshold is reached an action potential fires. Acetylcholinesterase hydrolyses acetylcholine, clearing the cleft so the signal ends and the synapse resets.

Rod cells in the mammalian retina detect light intensity. In darkness, retinal and opsin form rhodopsin, which keeps cation channels open so Na⁺ enters and the rod stays depolarised, releasing inhibitory neurotransmitter that reduces action potentials in optic neurones. Light isomerises retinal, changing rhodopsin and closing cation channels; Na⁺ entry falls, so the rod hyperpolarises. Less inhibitory transmitter is released, relieving inhibition of optic neurones, which depolarise and fire action potentials. Thus stimulus detection works by removing inhibition, and the brain interprets the changed impulse frequency.

Phytochrome is a photoreceptor protein whose two interconvertible forms, Pr and Pfr, absorb red light at about 660 nm and far-red light at about 730 nm. In daylight Pfr predominates; in darkness it slowly reverts to Pr, so the Pr:Pfr ratio reports day length and triggers flowering, germination and shade avoidance. IAA is auxin, a hormone that moves by polar transport from shoot tips and redistributes laterally in roots and shoots. It binds receptors such as TIR1, causing transcription factors to be degraded or activated, so genes for cell elongation, division and differentiation are switched on or off. Phytochrome acts through signalling proteins that alter transcription factor activity, so light cues change which genes are expressed.

Animals co-ordinate responses using two linked systems. Nervous control uses neurones: a stimulus depolarises a receptor membrane, action potentials travel along axons, and neurotransmitters cross synapses to pass the signal to an effector, giving rapid, short-lived, precisely targeted responses. Hormonal control uses endocrine glands that secrete hormones into the blood; hormones travel to target cells with complementary receptors and alter cell activity, giving slower, longer-lasting, widespread responses. The two systems interact: the hypothalamus links the nervous and endocrine systems, and the autonomic nervous system controls hormone release, for example adrenaline from the adrenal medulla during the fight-or-flight response.

The human brain is organised into regions with distinct locations and functions. The cerebral hemispheres form the largest, outermost part, divided into left and right halves by the longitudinal fissure and joined by the corpus callosum. They receive and integrate sensory information, initiate voluntary movement and support memory, language, reasoning and conscious thought. The hypothalamus lies below the thalamus, above the pituitary gland, and maintains homeostasis: it regulates body temperature, blood water potential, hunger and circadian rhythms, and controls pituitary secretions. The cerebellum sits at the back, beneath the cerebral hemispheres, and coordinates balance, posture and fine motor skills. The medulla oblongata is the lowest brainstem region, continuous with the spinal cord, and controls autonomic functions such as heart rate, breathing rate and blood pressure.

MRI uses strong magnetic fields and radio waves to align hydrogen nuclei; emitted signals build high-resolution images of soft tissue, so it reveals brain structure such as tumours, lesions and atrophy without ionising radiation. fMRI detects changes in blood oxygenation as a proxy for neural activity, mapping active brain regions during tasks and so investigating function. PET uses a radioactive tracer, often fluorodeoxyglucose labelled with fluorine-18, which emits positrons; annihilation produces gamma rays detected to show metabolic activity, useful for tumours and functional mapping. CT uses multiple X-ray projections from different angles to construct cross-sectional images; it is fast and excellent for bone and acute bleeding but uses ionising radiation. Together these techniques support diagnosis and investigation of brain structure and function.

The critical period is a limited window early in life when the visual cortex is highly plastic, so experience of clear images is needed for normal wiring. Hubel and Wiesel showed that covering one eye of a kitten during this window leaves cortical cells that should respond to that eye instead driven by the open eye, a shift that persists. After the window closes, similar deprivation has little effect, so the capacity to develop full visual function is largely fixed. The period ends as plasticity falls, linked to maturation of inhibitory circuits and closure of molecular brakes on synapse change. Both eyes must therefore receive focused, matching images while the window is open.

Animal models let researchers control sensory experience and record single cortical neurons, which cannot be done invasively in humans. Hubel and Wiesel used kittens and monkeys, suturing one eyelid or rearing with controlled visual input, then mapping ocular dominance in the visual cortex. Their results revealed columns of cells preferring one eye and showed that early deprivation shifts this balance, informing ideas about critical periods in human brain development. Such work raises ethical issues: invasive procedures on sentient animals need justification, and findings must be translated to humans cautiously because brains differ. Animal models therefore support human research rather than replacing ethical human studies.

This outcome asks you to discuss, not merely describe, the moral and ethical issues raised by using animals in medical research, and to do so from two ethical standpoints. A standpoint is a reasoned position, such as a utilitarian view weighing overall suffering against overall benefit, or a rights-based view holding that an animal's interests cannot be sacrificed for human gain. Take a concrete case: a new drug is tested on mice before human trials. From a utilitarian standpoint you might argue the suffering of a small number of mice is outweighed by lives saved; from a rights-based standpoint you might argue the mice's interests count equally and cannot be traded. Discussing means presenting both sides, using evidence, and reaching a justified judgement.

Habituation is a simple form of learning in which an animal, including a human, gradually stops responding to a repeated stimulus that proves harmless or unimportant. The response decreases because the stimulus carries no consequence, not because the animal is tired or unable to respond. A useful example is a person living near a railway: the first trains disturb sleep, but over time the same noise no longer wakes them, yet they still wake to an alarm clock. This shows the response to one specific stimulus has declined while other responses remain intact. Habituation saves energy and allows attention to be directed to new or significant stimuli, and it is distinct from sensory adaptation because it involves the nervous system learning about the stimulus.

This specification point requires you to understand that imbalances in naturally occurring brain chemicals can lead to ill health, with two key examples: dopamine in Parkinson’s disease and serotonin in depression. In Parkinson’s disease, the degeneration of dopamine-secreting neurons in the substantia nigra leads to reduced dopamine levels, causing motor symptoms such as tremors and rigidity. In depression, reduced serotonin activity is associated with low mood, although the exact mechanism is complex. You must also understand how this knowledge contributes to the development of new drugs, such as levodopa (L-dopa) for Parkinson’s and selective serotonin reuptake inhibitors (SSRIs) for depression. These drugs aim to restore neurotransmitter balance, but they may have side effects and variable effectiveness.

Drugs alter synaptic transmission by changing how neurotransmitters are released, received or removed. In Parkinson’s disease, dopamine-secreting neurones in the brain degenerate, so dopamine levels fall and movement becomes difficult to control. L-Dopa is a dopamine precursor that crosses the blood–brain barrier and is converted to dopamine by enzymes in the brain, partially restoring transmission at dopamine synapses. MDMA (Ecstasy) acts mainly on serotonin synapses: it is taken up by transporter proteins and causes serotonin to be released into the synaptic cleft, prolonging and intensifying stimulation. It also affects other monoamine transmitters. Understanding these examples shows how drugs can treat or disrupt nervous function.

Genome sequencing projects produce data about the base sequences of individuals and populations. In personalised medicine, a patient’s genome can be analysed to predict disease risk, guide drug choice and adjust dosage, because genetic variation affects how a person responds to treatment. For example, variants in genes coding for drug-metabolising enzymes can show whether a standard dose is likely to be effective or toxic. This raises social, moral and ethical issues: privacy and consent for genomic data, possible discrimination by insurers or employers, unequal access to testing and treatment, and the emotional impact of knowing future risk.

Genetic modification introduces a gene into a plant, animal or microorganism so it makes a useful drug. Microorganisms are common hosts: human insulin is produced by inserting the human insulin gene into a plasmid, transforming Escherichia coli, then culturing and purifying the protein. Plants can be engineered to make vaccines or antibodies, and animals can be engineered to secrete therapeutic proteins in milk. The drug is encoded by the inserted gene, so the host's transcription and translation machinery makes the product. Production requires a suitable promoter, a marker to identify transformed cells, and downstream extraction and purification. The drug must be tested for safety and activity before use.

Using genetically modified organisms has benefits and risks that must be weighed. Benefits include producing medicines such as human insulin, improving crop yield or nutritional content, and reducing pesticide use. Risks include genes escaping into wild populations, effects on non-target species, reduced biodiversity, and possible allergic or toxic effects of the new product. Ethical concerns include animal welfare and whether it is right to alter organisms. Risk assessment considers the likelihood and severity of harm, and controls such as containment, buffer zones and monitoring reduce risk. Decisions should be evidence-based and consider both scientific and social factors.

To investigate nature versus nurture in brain development, researchers use several methods. New-born babies show innate abilities, such as preference for face-like patterns, suggesting nature. Animal experiments, like Hubel and Wiesel's monocular deprivation in cats, show critical periods and nurture effects. Studies of damaged brain areas, such as Phineas Gage, reveal localisation and plasticity. Twin studies compare identical (monozygotic) and fraternal (dizygotic) twins: higher concordance in identical twins suggests genetic influence. Cross-cultural studies compare child-rearing practices across societies; universal milestones suggest nature, while variations suggest nurture. Each method has strengths and limitations, and evidence is often correlational, so causation must be inferred cautiously.

Habituation is a form of learning where repeated exposure to a harmless stimulus reduces the response. In this core practical, you investigate this using a simple model organism, such as the snail or a human volunteer. You present a stimulus, for example a light tap on the bench or a sound, and record the response, such as withdrawal of tentacles or a blink. After repeated presentations at regular intervals, the response should decrease. You must control variables: stimulus intensity, interval between stimuli, and environmental conditions. You then analyse the data to show a decrease in response over time. This practical illustrates synaptic changes, such as reduced neurotransmitter release, and is assessed through your ability to design, carry out, and evaluate the investigation.