Lect 1 Structure and Organisation of the NS PDF

Organisation of the nervous system & Neurotransmission Dr. Mohammad K. Hajihosseini BIO-5004A [email protected] October 2023  Functions of the Nervous System To co-ordinate and integrate multiple physiological systems/ functions To act in parallel with the En...

Organisation of the nervous system & Neurotransmission Dr. Mohammad K. Hajihosseini BIO-5004A [email protected] October 2023  Functions of the Nervous System To co-ordinate and integrate multiple physiological systems/ functions To act in parallel with the Endocrine System (hormonal communication) To enable rapid responses to external stimuli (eg. light, heat) or internal stimuli (e.g. blood pressure, osmotic pressure etc.) ‘Adaptive responses’ Responses may be simple, such as a reflex, or more complex, involving learning and memory (‘cognitive’) resulting in behavioural changes. 1  Why study Neuroscience? * Diseases Neurodegenerative; Demyelinating; Mood disorders Viral and bacterial infections of the Nervous system * Control of vital physiological functions e.g. appetite, blood pressure, sleep Drug companies spend millions on neuroscience research Funding bodies have dedicated panels to Neuroscience and Mental Health research Largest number of scientific journals dedicated to Neuroscience (>40) There is a large community of Neuroscientists (annual meetings attract 35000+ people) US: www.sfn.org UK: www.bna.org.uk Europe: www.networkglia.eu/en Federation of European Neuroscience Societies: www.FENS.org 2  Outline of the next three lectures Lecture 1: Structure and organization of the nervous system and its cell types Synaptic neurotransmission Lecture 2: Modulation of synaptic function, with a focus on the autonomic nervous system Lecture 3: Brain: anatomical and physiological subdivisions & its main neurotransmitters 3  Organization of the Nervous System Nervous System CNS PNS Brain Spinal cord Sensory Somatic System Autonomic Nervous Nervous System System 4  Organisation of the Nervous System The nervous system has two major subdivisions: - The Central Nervous System (CNS) - The Peripheral Nervous System (PNS) The division is purely anatomical – functionally, they are interconnected and interactive 5  Cell types found in the adult CNS (-Endothelial cells & Pericytes) Ependymal cells 6  Anatomy of a neuron (NB. this is a The basic unit of the nervous system Spinal motoneuron Structure with part of its axon – Cell Body In the PNS) Nucleus RER Mitochondria – Dendrites Outgrowths from cell body 1 – 500 000 per cell Receive inputs from other neurons – Axon Nerve fibre extending from axon hillock 1µm – 1m May be myelinated Contains microtubules – Axon terminal Synapse Release of neurotransmitter 7  Neuronal subtypes 3 functional classes: Abundance/ ratio: Afferent (sensory) neurons (1) – transmit information to the CNS – have sensory receptors at their peripheral end Efferent (motor) neurons (10) – transmit information from the CNS to the effector organs (muscle or gland) or other neurons Interneurons (200, 000) – transmit information from neuron to neuron – are found exclusively in the CNS – account for 99% of all neurons – can be inhibitory or excitatory – can be highly specialised e.g. in the retina 8  The Central Nervous System The Brain and Spinal cord – input regions of the sensory nerves – output regions of the motor nerves – many interneurons Grey matter contains: – interneurons, cell bodies and dendrites of efferent neurons, synapses and glia White matter contains: – axons (myelin sheaths). Contains descending and ascending fibre tracts or pathways Source: Vander, Sherman & Luciano Human Physiology McGraw-Hill 9  Glial cells Macroglia Microglia * Oligodendrocytes * Astrocytes There are 10 – 50 times more glial cells than neurons in the vertebrate CNS Functions of glial cells include: – Metabolic support eg. buffering extracellular Na+ and K+ ions – Removal of neurotransmitters from the extracellular space – Scavenger function – Control of the “blood-brain barrier” function – Guiding the growth of developing neurons (during embryonic stages) – Some glial cells may act as ‘neural stem cells’ 10 Organization of the Peripheral Nervous System Nervous System CNS PNS Brain Spinal cord Sensory Somatic System Autonomic Nervous Nervous System System Sympathetic Enteric Parasympathetic Nervous Nervous Nervous System System System 11  The Enteric nervous system - A meshwork of neurons innervating gut muscles as well as mucosal cells - Main role: peristalsis, but also important for/during gut bacteria interaction, infection and hyperactivity of autonomic nervous system (e.g. in Irritable Bowel syndrome (IBS)). 12 3  PNS: 12 pairs of Cranial Nerves * ‘On Old Olympus Towering Tops A Fin And German Viewed A House’ > Nerve fibres can be purely motor or sensory nerves, or a mixture of 13  PNS: Spinal Nerves 8 Cervical – neck, shoulder, arm & hand 12 Thoracic – Chest and abdominal wall 5 Lumbar – Hip & leg 5 Sacral – Genitals and lower GIT 14  The Autonomic Nervous System The autonomic nervous system provides motor control of the heart, smooth muscles and glands The sympathetic and parasympathetic nervous systems have a primary role in regulating the internal environment The sympathetic and the parasympathetic systems usually produce opposing physiological effects (‘dual innervation’) The sympathetic nervous system enables the body to respond to physiological stress (the fight-or-flight response) The parasympathetic nervous system promotes routine activities, conserving the body’s resources and restoring homeostasis (rest and digest) 15  Parasympathetic Sympathetic Axons Axons emerge from emerge from thoracic and cranial and lumbar sacral regions regions Anatomical differences! 16 Some effects of the autonomic nervous system Target Organ Sympathetic Parasympathetic Eye Dilates pupil Constricts pupil Contracts ciliary muscle Heart Increases rate and force of Decreases rate and force contraction of contraction Arterioles Constricts (↓flow to organs; ↑bp) Exceptions: dilation in skeletal muscle and coronary circulation Lungs Relaxation of bronchial smooth Contraction of bronchial muscle smooth muscle Gut ↓motility ↑motility Contraction of sphincters Relaxation of sphincters Liver Glycogenolysis Gluconeogenesis Bladder Relaxation Contraction 17  Spinal ganglia – concept of ‘pre’ and ‘post ganglionic’ neurons and fibres 18  In the Sympathetic Nervous System: Pre-ganglionic sympathetic neurons: – Leave from the thoracic and lumbar regions of the spinal cord (thoracolumbar system) – Synapse at ganglia close to the spinal cord – Are cholinergic – the neurotransmitter released is acetylcholine (ACh) – Innervate the adrenal medulla causing release of adrenaline into the bloodstream Post-ganglionic sympathetic neurons are noradrenergic – the neurotransmitter released at the neuron-effector organ synapse is noradrenaline (NA) 19  In the Parasympathetic Nervous System Pre-ganglionic parasympathetic neurons – Leave from the brainstem and the sacral region of the spinal cord (cranio-sacral system) – Synapse at ganglia close to the effector organ – Are cholinergic – the neurotransmitter released is acetylcholine (ACh) Post-ganglionic parasympathetic neurons are cholinergic - ACh is released at the neuron-effector organ synapse 20 21  Overview of neurotransmitters in the PNS ACh – acetylcholine NE – norepinephrine = noradrenaline Epi – epinephrine = adrenaline 22 Synapse and synaptic transmission 23  General anatomy of a synapse and synaptic organization Neurons can have a ‘1 to 1’ or ‘1 to many’ synaptic contacts 24  3-dimensional structure of a synaptic bouton (in the CNS) A typical synapse is composed of at least 60 different proteins (which play structural roles but as well as trafficking of molecules) Wilhelm et al. 2014 Science pages 1023- 1028 25  Dendritic arborization is critical to neuronal function Computational modelling Purkinje cell in the cerebellum of neural connectivity * There are 1014 synapses in the CNS 26  Neurons can make synapses in vitro GFP-reporter construct Neurons cultured as a monolayer on a petri-dish Neural networks & artificial intelligence 27  The Neuromuscular Junction is a specialized synaptic structure The neuromuscular junction is a specialised synapse between an α-motor neuron and a muscle fibre at the motor end plate One α-motor neuron synapses with several muscle fibres - ‘the motor unit’ The α-motor neuron originates from the CNS with its cell body in the grey matter of the spinal cord or brain stem α-motor neurons are fast, myelinated neurons Their neurotransmitter is acetylcholine 28  The Neuromuscular Junction (NMJ) -Neurons make contact with muscle fibres at specific points Unlike synapses in the CNS, NMJ is ‘covered’ by Schwann cells 29 Synaptic transmission at the Neuromuscular Junction (part of PNS) 30  Neurotransmission The Myotatic (knee jerk or stretch) Reflex NB. The sensory neurons form a divergent pathway, whilst motor neurons form a convergent pathway 31  EPSPs (Excitatory Post-Synaptic Potentials) Up to -90 in some neurons EPSPs depolarize the post-synaptic membrane EPSPs are most commonly the result of increased Na+ or Ca2+ permeability 32 IPSPs (Inhibitory Post-Synaptic Potentials) IPSPs hyperpolarize the post-synaptic membrane IPSPs are usually the result of increased Cl- or K+ permeability 33  Synaptic Integration There may be thousands of synaptic inputs on one post- synaptic cell – some excitatory, some inhibitory EPSPs and IPSPs interact – synaptic integration Summation of the EPSPs and IPSPs determines the final post-synaptic cellular response Source: Vander’s Human Physiology. McGraw-Hill 34  Neurotransmitters – definition There are in excess of 50 different neurotransmitters Neurons are named after the neurotransmitter that they release (eg. cholinergic, noradrenergic) In order to be considered a neurotransmitter the substance should fulfil four criteria: 1. It is synthesized in the neuron 2. It is present in the presynaptic terminal and is released in amounts sufficient to exert an effect on the postsynaptic cell 3. When applied exogenously it mimics exactly the action of the endogenously released transmitter 4. A specific mechanism exists for removing it from the synaptic cleft 35  Common neurotransmitters There are 9 classical low molecular weight neuro-transmitters, all of which are amines: Acetylcholine Biogenic amines Noradrenaline Adrenaline Dopamine Serotonin (5-HT) Histamine Amino acids Glutamate GABA Glycine Other molecules which can act as neurotransmitters/ neuro- modulators include: ATP and adenosine, nitric oxide (NO; ‘laughing gas’) In addition there are more than 50 peptide neurotransmitters 36  Reading Silverthorn - Human physiology (Pearsons) Vander’s Human Physiology Widmaier, Raff & Strang. McGraw-Hill (Basic text) Principles of Neural Science Kandel, Schwartz & Jessel. McGraw-Hill (Advanced) Web (for primary articles and reviews) www.ncbi.nlm.nih.gov Type in your ‘key word’ and ‘review’ * Journal: Nature Neuroscience reviews