Nerves, Synapses, and NMJ 2024-25 PDF

Graduate Accelerated Programme 2022/24 Nerve, Synapse and NMJ Raymond Macharia, BVetMed., MSc., PhD., PGCAP., MSc VetEd., FHEA Associate Professor of Neuromuscular Science Email: [email protected]...

Graduate Accelerated Programme 2022/24 Nerve, Synapse and NMJ Raymond Macharia, BVetMed., MSc., PhD., PGCAP., MSc VetEd., FHEA Associate Professor of Neuromuscular Science Email: [email protected] Hobday building, 4th Floor room 08 Office:Name Author Created by Learning Design  Nerve, Synapse and NMJ Learning Objectives (LOs) 1. Describe the general organisation and functions of the nervous system. 2.Describe the cellular composition of the nervous system and functions. 3.Describe the general structure of a nerve cell 4.Explain how action potentials are generated and propagated 5.Describe the functional anatomy of a synapses and the neuromuscular junction (NMJ) 6.Describe the production, release, action and degradation of the principal neurotransmitters ▪ Learning Outcomes  Nerve, Synapse and NMJ LO1: General Organization and Function of the Nervous System Components Sensory Integration Response component component component A 3-component system that is seamlessly interconnected Sensory - sensory organs and sensory neurones) Integration- Spinal cord and Brain Response- Motor neurons and effector organs ( muscles/glands)  Nerve, Synapse and NMJ LO1: General Organization and Function of the Nervous System Spinal Cord and Neuronal Connections Nerve, Synapse and NMJ  Nerve, Synapse and NMJ LO 1: General Organization and Function of the Nervous System Morphology Nervous system divided morphologically into 2 parts: ▪ Peripheral Nervous system (PNS) - interface between CNS and the environment. This includes sensory and motor neurons. ▪ Central Nervous System (CNS) – Composed of the Brain and Spinal cord.  Nerve, Synapse and NMJ LO 2: Cellular composition of the nervous system and functions Peripheral nervous system Sensory fibres Carry sensory information from receptor organs (skin, viscera, proprioceptors). Motor fibres ▪ Somatic motor (Voluntary system) ▪ Autonomic nerves (sympathetic and parasympathetic) Respond to the CNS inputs directly or the result of sensory input.  Nerve, Synapse and NMJ LO 2: Cellular composition of the nervous system and functions Neurones and Neuroglia Communication system (Neurons- specialized cells). Neurone types ▪ Bipolar ▪ Unipolar/Pseudo-unipolar ▪ Multipolar Support matrix (Neuroglia). Neuroglia types ▪ Astrocytes- nourish and support neurones ▪ Oligodendrocytes- Increase speed of impulses during neurotransmission ▪ Microglia- phagocytes that remove necrotic material. ▪ Ependymal cell- specialized cells of the epithelium lining CNS cavities  Nerve, Synapse and NMJ LO 2: Cellular composition of the nervous system and functions Neurones Communication system (Neurons- specialized cells). Neurone types ▪Bipolar ▪Unipolar /Pseudounipolar ▪Multipolar  Nerve, Synapse and NMJ LO 2: Cellular composition of the nervous system and functions Neuroglia Support matrix for neurones  Nerve, Synapse and NMJ LO 3: Structure of a nerve cell The Neurone is made up the of the following parts: ▪ Cell body (soma) - Contains nucleus and other organelles ▪ Dendrite - Cellular extension containing microtubules and neurofilaments ▪ Axon - Arise from the soma (or dendrite) in a specialised region called the axon hillock ▪ Schwann cell - comprise the myelin sheath (some nerves) ▪ Node of Ranvier-Intervals between Schwan cells. ▪ Axonal terminal- pre-synapse Nerve, Synapse and NMJ LO 3: Structure of a nerve cell  Nerve, Synapse and NMJ Summary of LOs1-3 The functional unit of the nervous system is the neuron Nervous system made up of CNS and PNS Neurons in PNS are either sensory or motor Neurons coexist with Neuroglia (support matrix)  Nerve, Synapse and NMJ LO 4: Action Potentials-generation and propagation Membrane Structure ▪ Phospholipid bilayer ▪ Protein molecules Receptor proteins- bind neurotransmitter Channel proteins- form pore for ion movement Transport proteins-Bind and transfer ions (K+ and Na+)  Nerve, Synapse and NMJ LO 4: Action Potentials-generation and propagation Membrane Structure  Nerve, Synapse and NMJ LO 4: Action Potentials-generation and propagation Resting membrane Has selective permeability to proteins and ions ▪ Readily permeable to K+ ions ▪ Slightly permeable to Na+ ions ▪ Impermeable to large number of negatively charged proteins and anions ▪ Due to large number of anions in the cell, K+ is continuously drawn into the cell – this is an electromotive force  Nerve, Synapse and NMJ LO 4: Action Potentials-generation and propagation Sodium-Potassium pump The transmembrane pump uses cellular energy to: ▪ Move Na+ out of cell ▪ Move K+ into the cell Due to a selective i) membrane permeability (see previous slide) and ii) Na/K+ pump, the charged particle distribution in the neuronal environment is not uniform.  Nerve, Synapse and NMJ LO 4: Action Potentials-generation and propagation Resting membrane potential ▪ Na+ conc. higher outside cell ▪ K+ conc. and anions higher inside cell ▪The resulting difference in charged particles leads electrical potential across the membrane; this is the Resting membrane potential (RMP) and is normally -75mV  Nerve, Synapse and NMJ LO 4: Action Potentials-generation and propagation Nerve cell conductance-Action Potential 3 stages: Depolarisation ▪ Stimulation cause membrane permeability to Na+ to increase thereby raising the resting membrane potential. Threshold- AP generated ▪ Critical voltage (+30mV) reached and voltage-sensitive Na+ and K+ channels undergo conformational change. ▪ Permeability to Na+ abruptly increase but K+ increase slowly. Repolarisation ▪ Na+ gates close at +35mV and K+ gates fully open removing K+ outside and transmembrane potential becomes negative.  Nerve, Synapse and NMJ LO 4: Action Potentials-generation and propagation Nerve cell conductance-Action Potential generation K+ K+ K+ K+ K+ Na+Na+ Na+Na+ Na+ Na+/K+ pump  Nerve, Synapse and NMJ LO 4: Action Potentials-generation and propagation Nerve cell conductance and Action Potential generation Na+ rapidly enter the cell via ion channels Threshold is reached (+30mV) Na+ channels close at +35 mV K+ move out of the cell via the ion channels thereby reversing (re-establishing) the membrane potential to the original -75mV  Nerve, Synapse and NMJ LO 4: Action Potentials-generation and propagation Nerve cell conductance Dependent on: ▪ Myelination- Insulate the fibre reducing ion leaks ▪ Node of Ranvier- Saltatory effect ▪ Diameter of fibres- the higher the diameter the greater the velocity = more surface area for ion diffusion  Nerve, Synapse and NMJ Summary LO4- Nerve conductance based on selective membrane permeability to Ions and proteins Critical voltage is needed to achieve an AP AP propagation dependent on myelination  Nerve, Synapse and NMJ LO 5: anatomy of a synapses and the neuromuscular junction Synapse  Nerve, Synapse and NMJ LO 5: anatomy of a synapses and the neuromuscular junction Synapse  Nerve, Synapse and NMJ LO 5: Functional anatomy of a synapses and the NMJ Signal transduction Arrival of an Action Potential (AP). Ca++ influx Fusion of vesicles with pre-synaptic membrane. Exocytosis of neurotransmitter (NT). Diffusion of NT across the synaptic cleft and binding to post-synaptic receptors leading to muscle contraction. NTs removed by enzymatic breakdown (AchE) or reuptake across the pre- synaptic membrane for recycling. The effect of a NT on the post-synaptic neuron can be either excitatory or inhibitory.  Nerve, Synapse and NMJ LO 5: anatomy of a synapses and the neuromuscular junction Synapse  Nerve, Synapse and NMJ LO 6: Production, release, action and degradation of neurotransmitters Neurotransmitters ▪ Neurotransmitters (NT) are mainly peptides or derived from amino acids. ▪ 3 types - excitatory, inhibitory and modulatory ▪ NTs are synthesized in the Nerve cell body and transported along the axon to the pre-synaptic terminal where they are stored in vesicles ▪ The receptors (on the post-synaptic membrane) determine the effects of the NT.  Nerve, Synapse and NMJ LO 6: Production, release, action and degradation of neurotransmitters Neurotransmitters Acetylcholine (Ach)- Released at neuromuscular junctions and in ANS. Receptors are either nicotinic or muscarinic. Catecholamines - Norepinephrine (Noradrenaline) Acts on adrenoceptors (α1, α2; ß1,ß2) Glutamate - Excitatory within the brain Glycine - inhibitory within spinal cord Gama-aminobutyric acid (GABA)- Inhibitory within CNS Others- Serotonin, Dopamine, and neuropeptides  Nerve, Synapse and NMJ LO 6: Production, release, action and degradation of neurotransmitters Acetylcholine receptors Nicotinic: Found in the NMJ and autonomic nervous system (ANS) pre-ganglionic neurons Muscarinic: Found in post-ganglionic neurons of parasympathetic nerves  Nerve, Synapse and NMJ LO 6: Production, release, action and degradation of neurotransmitters Adrenergic receptors ß1 receptors- myocardium- excitatory ß2 receptors- smooth muscle relaxation α1 receptors – smooth muscle contraction  Nerve, Synapse and NMJ LO6: Production, release, action and degradation of neurotransmitters Acetylcholine and adrenergic receptors  Nerve, Synapse and NMJ LO 5&6 Summary Synthesis of the neurotransmitter- Takes place in the cell body, in the axon, or in the axon terminal. Storage of the neurotransmitter- granules or vesicles in the axon terminal. Calcium enters the axon terminal during an action potential, causing release of the neurotransmitter into the synaptic cleft. The transmitter binds to and activates a receptor in the postsynaptic membrane. Deactivation: Neurotransmitterter is either destroyed enzymatically, or taken back into the nerve terminal to be reused, or degraded and removed  Nervous System Further reading Human Physiology-12 and 13th edition, Stuart Ira Fox., pp162- 200 (13th Ed) Veterinary Neuroanatomy- C Thompson and C Hahn pp1-10 Principles of Animal Physiology- 2nd Edition. Christopher D. Moyes and Patricia M. Schulte., pp 168-221  Nervous System One Health relevance of NOSS teaching Significance to animal health and welfare The nervous system is integral to the control of many complex physiological and biochemical process in an animal’s body. Understanding the normal and abnormal behaviour in animals is important for timely health interventions. Significance to public health Direct or indirect disturbances in the nervous system function affect an animal’s behaviour, productivity and the human-animal bond. Significance to ecosystem health and sustainability The nervous system is involved in complex process such as locomotion, behaviour patterns and feeding that ultimately have direct and indirect impacts on the food chain.