HUBS1416 Topic 3 Neurotransmitters, receptors and integration of electrical signals.pdf

School of Biomedical Science and Pharmacy College of Health, Medicine & Wellbeing Neurotransmitters & Receptors and Integration of Electrical Signals Advanced Human Bioscience HUBS1416 School of Biomedical Science and Pharmacy College of Health, Medicine & W...

School of Biomedical Science and Pharmacy College of Health, Medicine & Wellbeing Neurotransmitters & Receptors and Integration of Electrical Signals Advanced Human Bioscience HUBS1416 School of Biomedical Science and Pharmacy College of Health, Medicine & Wellbeing  Lecture Overview Part 1: Neurotransmitters, Receptors, the Synapse & CNS effects Part 2: Autonomic Receptors & Neurotransmitters Part 3: Integrating Electrical Signals & Reflexes Neurotransmitters & Receptors Key neurotransmitters l Autonomic parasympathetic: l Autonomic sympathetic: l Somatic (at the muscle): l CNS/Brain: Many disorders are thought to be due to inappropriate levels of neurotransmitters Normal Depression Schizophrenia Parkinson’s Mania Dementia  Treatment of many conditions involves manipulation of neurotransmitters and/or their interaction with their receptors For example, treatment of depression could involve l Monoamine oxidase inhibitors (MAOIs) l Selective serotonin reuptake inhibitors (SSRIs) l Noradrenaline-serotonin reuptake inhibitors (NSRIs) l Selective Noradrenaline reuptake inhibitors (SNRIs) l Noradrenaline-dopamine reuptake inhibitors (NDRIs) Response produced MA Synaptic transmission involving monoamine O neurotransmitters ends after they have had their effect because of re-uptake and enzymatic breakdown of the neurotransmitter by MAO and COMT T M CO MA If the effect needs to last longer this can O MA OI be achieved by increasing the s concentration of monoamine NRIs neurotransmitters by blocking re-uptake or blocking enzymatic breakdown by MAO NSRIs SSRIs  Side effects of targeting neurotransmitters for medicinal purposes It is important to remember that the same neurotransmitter can be used by various different neurons for the purpose of generating different responses This means that ‘targeting’ the neurotransmitter to treat one condition can lead to side-effects affecting different body systems Eg. Improving depression can cause nausea, hypertension, digestive issues, etc. Pain is both a sensory and an emotional experience Pain is detected by nociceptors Narcotic analgesics Non-steroidal anti-inflammatories  Stress-induced analgesia l endogenous opioids and their neurons form a pain modulation system that operates during extreme stress l “damps down” pain signals when it might be detrimental to be experiencing extreme pain Autonomic Functions  Autonomic Neurotransmitters l Sympathetic division (fight or flight): l Parasympathetic division (rest & restore):  Receptors for Acetylcholine - Cholinergic receptors There are two main types Nicotinic Muscarinic Found in brain & on organs Found on skeletal muscle & glands Produce contraction Produce parasympathetic response  Receptors for Noradrenaline - Adrenoceptors There are two main types α β β3 Found in fat cells - Causes α1 α2 β1 β2 mobilisation of fat Found on blood vessels - Causes constriction Found in the brain. A Found on the presynaptic receptor heart only - Found in bronchioles which Ü further Causes Û rate & and blood vessels - noradrenaline release strength of beat Causes dilation of both from the neuron  Sympathetic effects Parasympathetic effects Pupillary constriction (M) Dilation of pupil (α) Lens accommodates Flattening of lens & Û aqueous (ciliary muscle contracts) (M) humour production (β) Lacrimation (M) ↓ Secretion & blood flow (α) ↑ Secretion & blood flow (M) Localised sweating (α) Large ↑ in secretion (M) Bronchodilation (β) Generalised sweating (M) ↑ Heart rate, ↑ contractility (β) Bronchoconstriction (M) ↑ Glycogenolysis (β) Bronchial gland secretion ↑ ↑(M) ↑ Renin secretion (β) ↓ ↓ Heart rate, small ↓ contractility (M) Motility ↓ (α, β), Motility ↑, sphincter tone ↓, sphincter tone ↑ (α) secretion ↑ (M) Detrusor relaxation (β), Detrusor contraction (M), sphincter contraction (α) sphincter & trigone relaxation ↑ Contractility & glycogenolysis (β)  Integration in the nervous system Integration: “bringing together of different parts to make a whole” l Each neuron integrates many inputs (some inhibitory, some excitatory) l Response is either generation of or inhibition of an action potential l Allows the nervous system to process a huge amount of information very quickly, and produce appropriate responses  Excitatory vs Inhibitory Signals Excitatory – the membrane potential depolarises so that an action potential is generated Inhibitory – the membrane potential hyperpolarises so that an action potential is prevented l The effect is determined by the receptor and neurotransmitter combination  Integration in the nervous system Integration: “bringing together of different parts of make a whole” l A single neuron integrates all its many inputs, some inhibitory, some excitatory l Involves multiple types of neurotransmitters & receptors l A single neuron can have synapses with multiple other neurons –multiple different neurotransmitters released to it at the same time l The end effect – integration – is dependent on which is the strongest &/or longest lasting combination  Control loops in the nervous system Interneurons Central integrator Efferent (motor) Afferent (sensory) (CNS) neurons neurons This change is detected by We do something about it our sensory systems (motor output) Something happens in our environment (internal or external) We have responded to the change in some way  The simplest reflex – the stretch reflex 2. The stretching of the 3. Action potentials travel muscle is detected by along the sensory neuron 1. The muscle is sensory organs in the into the spinal cord stretched by tapping its muscle tendon with a hammer 4. The sensory neuron synapses with a motor neuron in the grey matter of the spinal cord 5. The motor neuron to the muscle generates action potentials which cause the muscle to contract 23 A more complicated reflex loop – the withdrawal reflex 1. The hand 2. Pain sensors in the skin are accidentally stimulated, causing action touches the hot potentials to flow along the pain pan sensory neurons into the spinal cord 3. The pain neuron synapses with three other neurons. The result is: 4. The effect of the a) stimulation of the motor neuron to the biceps commands to the muscle muscles is removal of b) inhibition of the motor neuron to the triceps the hand from the muscle source of the heat 24the brain c) signalling of the pain sensation to Reflexes therefore involve both peripheral & central and sensory & motor divisions of the nervous system. They can also be somatic or autonomic: Reflexes l Quick l Stereotyped l Automatic (not consciously controlled) l Can involve cranial nerves or spinal nerves l Can involve spinal cord or brain l Can be somatic or autonomic l Can be innate or acquired l Some are present early in life, but are over-ridden later in life Some primitive somatic reflexes present from birth The Moro reflex The Babinski Normally inhibited (plantar withdrawal) reflex around 4 Inhibited at 1-2 yrs of age months of age The grasping reflex The Stepping reflex (palmar & plantar) Normally inhibited around 3 months Normally inhibited around 6 of age months of age The rooting reflex