Mental Health Fundamentals of neurobiology - PowerPoint Presentation

1. Mental HealthFundamentals of neurobiology

2. Introduction to neurobiologyMental Health2

3. Mental HealthTo understand psychiatric disorders, it is important to understand the normal structure and function of the nervous systemThe central nervous system (CNS; brain, spinal cord) and peripheral nervous system (PNS) are composed of two main types of neural cells:1,2Neurones – basic nerve cells, which transmit messages throughout the nervous system, resulting in functions as diverse as tasting, thinking, and movingGlial cells – provide structural and functional support to neuronesMicroglia provide a phagocytic role: destroy invading microorganisms, removing cell debris, and promoting tissue repairMacroglia include oligodendrocytes, Schwanm cells, astrocytes, and ependymal cells, which have a variety of supportive functions within the nervous systemOrganisation of the nervous system1. Tortora & Derrickson. Principles of Anatomy and Physiology. 12th edition. 2009;2. Martin. Neuroanatomy Text and Atlas. 3rd edition. 2003 3

4. Mental HealthNeurones1. Martin. Neuroanatomy Text and Atlas. 3rd edition. 2003; 2. Kandel et al. Principles of Neural Science. 4th edition. 2000; 3. Tortora & Derrickson. Principles of Anatomy and Physiology. 12th edition. 2009; 4. Oxford Concise Medical Dictionary. 2nd edition. 19984Cell bodyThe cell body contains the cellular machinery that keeps the neurone alive, e.g., the nucleus1Myelin sheathThe myelin sheath is a whitish, fatty layer that wraps around the axons of most neurones and serves to increase the transmission speed of an action potential along the axon1Axons with a myelin sheath are known as ‘myelinated axons’2Axon terminalsAxon terminals are the regions at the end of an axon that release neurotransmitters1DendritesDendrites receive information from other neurones1Each neurone typically has more than one dendrite3NucleusThe nucleus is critical for the neurone’s vitality; it contains the genetic material (genes) needed for cell division/ development, and protein synthesis1,4AxonMost neurones have a single axon3An axon transmits the signal generated by the neurone (the action potential) through the nervous system1Information flowInformation flow

5. Mental HealthAnatomical regions of the brain1. Kandel et al. Principles of Neural Science. 4th edition. 2000; 2. Tortora & Derrickson. Principles of Anatomy and Physiology. 12th edition. 20095CORPUSCALLOSUMDiencephalon The diencephalon is surrounded by the cerebral hemispheres and includes:1Thalamus The thalamus is a relay station for all sensory information (except smell) from the PNS to the cerebral cortexHypothalamusThe hypothalamus is a major regulator of internal body functions, such as eating, drinking, maternal behaviour, and sleep cycles; it also plays a role in motivation through initiating and maintaining behaviours a person finds rewardingCerebrumThe cerebrum is known as the ‘seat of intelligence’.2 It is divided into two hemispheres and is made up of three basic regions (see next slide)CerebellumThe cerebellum is a highly folded structure located at the posterior of the brain. It is important in maintaining posture and for coordinating head and eye movements, and is also involved in fine tuning of muscle movements and in learning motor skills1Spinal cordMidbrainBrainstemLocated between the spinal cord and the cerebrum, the brainstem is involved in involuntary functions, such as control of blood pressure and breathing, as well as arousal1PonsMedullaoblongata

6. Mental HealthCerebrum1. Price & Wilson. Pathophysiology: Clinical Concepts of Disease Processes. 6th edition. 2003; 2. Tortora & Derrickson. Principles of Anatomy and Physiology. 12th edition. 2009; 3. Martin. Neuroanatomy Text and Atlas. 3rd edition. 20036SulciCerebral cortexThe cerebral cortex is the main functional unit of the cerebrum, a layer of grey matter (neuronal cell bodies and dendrites) 2–4 mm thick on the outer surface of the brain that is essential for conscious behaviour2The surface of the cerebral cortex is characterised by raised ridges of tissue called gyri, separated by shallow grooves called sulci1GyriGrey matterGrey matter is made up of neuronal cell bodies, dendrites, and axon terminals3White matterWhite matter consists of glial cells and bundles of myelinated axons that relay messages between the cerebral cortex and other parts of the CNS3The cerebrum is divided into two hemispheres that receive sensory information from, and control the movement of, the opposite side of the body1The cerebrum is made up of three main regions:1,2The cerebral cortexThe underlying white matter Several subcortical structures, including the basal gangliaBasal gangliaDeep below the cerebral cortex are interconnected nuclei, collectively known as the ‘basal ganglia’2

7. Mental HealthLobes of the brainDeep grooves, called fissures, separate the lobes of the brain:1Each cerebral hemisphere has four lobes that can be identified on the surface of the brain2,3A fifth lobe, the insula, lies deep within the brain21. Price & Wilson. Pathophysiology: Clinical Concepts of Disease Processes. 6th edition. 2003; 2. Tortora & Derrickson. Principles of Anatomy and Physiology. 12th edition. 2009; 3. Martin. Neuroanatomy Text and Atlas. 3rd edition. 2003 7

8. Neurosynaptic transmissionMental Health8

9. Electrical neurotransmission1Following sufficient excitatory stimulation of the neurone, an action potential is generated at the origin of the axonMental HealthNeurotransmission1. Adapted from: Kandel et al. Principles of Neural Science. 4th edition. 20009Chemical neurotransmission1When the action potential reaches the axon terminal it stimulates the release of chemical neurotransmittersInformation flow

10. Neurones do not physically touch one another; two neurones are separated by a gap, known as a synaptic cleft1Binding of chemical signals to the postsynaptic neuron can:Excite – increasing the generation of action potentials Inhibit – decreasing the generation of action potentialsInduce other biochemical processes 1Mental HealthThe synapse1. Kandel et al. Principles of Neural Science. 4th edition. 200010

11. An action potential reaches the axon terminal of the presynaptic neurone1Vesicles fuse with the cell membrane of the presynaptic neurone, causing an influx of calcium ions, which causes the neurone release stored neurotransmitters into the synaptic cleft1The neurotransmitters cross the synaptic cleft and bind to specific receptors on the postsynaptic neurone1Depending upon the receptor type, when a neurotransmitter binds to the receptor on the postsynaptic neurone it can either act by:2Rapidly opening or closing an ion channel in the cell membrane, thereby generating or inhibiting an action potentialSynthesising a second messenger (e.g., cyclic AMP) Releasing calcium ions (Ca2+) that may interact in a wide variety of biochemical processesThe neurotransmitters are cleared from the synaptic cleft by:3,4Reuptake into the presynaptic neuroneRemoval by astrocytesDiffusion away from the synapseBreakdown by enzymesMental HealthProcess of chemical neurotransmissionAMP = adenosine monophosphate1. Purves et al. Neuroscience. 4th edition. 2008;2. Tortora & Derrickson. Principles of Anatomy and Physiology. 12th edition. 2009; 3. Kandel et al. Principles of Neural Science. 4th edition. 2000; 4. Sadock et al. Kaplan & Sadock’s Comprehensive Textbook of Psychiatry. 9th edition. Vol 1–2. 2009111234512345

12. NeurotransmittersMental Health12

13. Mental HealthNeurotransmitters and receptorsNMDA = N-methyl-d-aspartate; AMPA = α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; GABA = gamma-aminobutyric acidKandel et al. Principles of Neural Science. 4th Edition. 2000; 2. Purves et al. Neuroscience. 4th Edition. 2008; 3. Stahl. Stahl’s Essential Psychopharmacology. Neuroscientific Basis and Practical Applications. 4th Edition. 2013; 4. Wierońska et al. Pharmacol Ther 2016;157:10–27; 5. Grieg et al. Recent Pat CNS Drug Discov 2013;8(2):123–141; 6. Sadek & Stark. Neuropharmacology 2016;106:56–7313NeurotransmitterReceptor subtypesDopamineDopaminergic receptors (D1-5 subtypes)Serotonin5-HT receptors (5-HT1A-F, 5-HT2A-C, 5-HT3-7 subtypes)GlutamateIonotropic receptors: AMPA, kainate, NMDA receptors;metabotropic receptors (mGluR1-8 subtypes)4GABAGABAA-C subtypesNoradrenalineα-adrenergic receptors (α1A-C, α2A-C subtypes);β-adrenergic receptors (β1-3 subtypes)AcetylcholineCholinergic receptors: muscarinic receptors (M1-5 subtypes);5nicotinic receptorsHistamineHistaminic receptors (H1-4 subtypes)6Neurotransmitter receptor subtypes1-3

14. Mental HealthGlutamateGlutamate is the principal excitatory neurotransmitter in the CNS1Glutamate is an amino acid that is produced from glutamine1Glutamate is removed from the synapse by transporters on glial cells, metabolised to glutamine, then resupplied to the relevant neurone terminals1CNS = central nervous system1. Purves et al. Neuroscience. 4th edition. 2008; 2. Stahl. Stahl’s Essential Psychopharmacology. 201314Cortico–brainstem glutamate projection2Regulates neurotransmitter release from the brainstemCortico–striatal glutamate pathway2Thalamo–cortical glutamate pathways2This pathway innervates pyramidal neurones in the cortexCortico–thalamic glutamate pathways2Hippocampal–striatal glutamate pathway2Cortico–cortical glutamate pathways2These can be direct, or indirect via GABA neuronesHOOOOHNH2

15. Mental HealthGABAGABA is found throughout the brain, rather than being localised to specific areas or pathways1There are three types of GABA receptor, which although varied can typically be separated as follows:1GABAA – ionotropic chloride channelGABAB – metabotropic G-protein coupled receptorGABAC – ionotropic chloride channelGlycine, the other major inhibitory neurotransmitter, has a more localised distribution (about half of the inhibitory synapses in the spinal cord use glycine); it is used as a co-transmitter on NMDA receptors1,2Most inhibitory neurones in the brain use GABA or glycine – as many as a third of the inhibitory synapses in the brain use GABA1The predominant precursor for GABA is glutamate1GABA is removed from the synapse by specific transporters1GABA = gamma-aminobutyric acid1. Purves et al. Neuroscience. 4th edition. 2008; 2. Stahl. Stahl’s Essential Psychopharmacology. Neuroscientific Basis and Practical Applications. 4th edition. 201315H2NOOH

16. Mental HealthDopamineDopamine is produced from the precursor molecule DOPA (dihydroxyphenylalanine) by DOPA decarboxylase1Dopamine is removed from the synapse by specialised dopamine transporters, and is catabolised by monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT)1Dopamine is involved in movement control, motivation, reward, and reinforcement; many addictive substances work by affecting dopaminergic neurones1-31. Purves et al. Neuroscience. 4th edition. 2008; 2. Kandel et al. Principles of Neural Science. 4th edition. 2000; 3. Stahl. Essential Psychopharmacology. 2013Mesocortical pathwayHere, dopamine influences perception, cognition, and social behaviour2,3Nigrostriatal pathway Dopamine has influence over control of fine movements and initiation of movement2,3Tuberoinfundibular pathwayDopamine normally inhibits the release of prolactin3Mesolimbic pathwayDopamine is thought to be involved in emotion and memory, pleasurable sensations and reward, the euphoric effects of addictive substances, as well as psychotic symptoms, such as delusions and hallucinations2,3HONH2HO

17. Mental HealthNoradrenalineNoradrenaline (also called norepinephrine) is a neurotransmitter of neurones in the locus coeruleus1,2The principal function of the locus coeruleus is to prioritise competing incoming stimuli, whether external (e.g., a threat from the environment) or internal (e.g., pain), and to focus attention11. Stahl. Stahl’s Essential Psychopharmacology. Neuroscientific Basis and Practical Applications. 2nd edition. 2000; 2. Purves et al. Neuroscience. 4th edition. 2008; 3. Dunn & Swiergiel. Eur J Pharmacol 2008;583:186–19317CerebellumThe noradrenergic projections to the cerebellum is thought to mediate motor movements, especially tremor1Spinal cordThe noradrenergic projection to the brainstem controls blood pressure1Prefrontal cortexSome noradrenergic projections to the frontal cortex are thought to help regulate mood; others are thought to mediate attention1The noradrenergic projection to the limbic cortex is thought to mediate emotions, energy, fatigue, and psychomotor agitation/retardation1Locus coeruleusNoradrenergic projections from the locus coeruleus project to the back of the brain, and are important in arousal and attention1-3HONH2HOOH

18. Mental HealthSerotoninSerotonin (also known as 5-HT) is a neurotransmitter that is found throughout the body.1 High concentrations are found in the CNS, platelets, and certain cells in the gastrointestinal tract1There are many receptor subtypes for serotonin; the roles of these receptor subtypes are not fully elucidatedSerotonergic neurones project widely throughout the brain from their origin in the raphe nuclei of the brainstem2,3CNS = central nervous system1. Brunton et al. Goodman & Gilman’s the Pharmacological Basis of Therapeutics. 11th edition. 2006; 2. Purves et al. Neuroscience. 4th edition. 2008; 3. Stahl. Stahl’s Essential Psychopharmacology. Neuroscientific Basis and Practical Applications. 4th edition. 201318Spinal cordSerotonergic projections to the spinal cord may regulate pain3Cerebral cortexWithin the forebrain, serotonin is thought to regulate sleep and wakefulness2Raphe nucleiNH2HONH