Cellular Overview Neuroscience I PDF

Cellular Overview PT 8203 - Neuroscience I Rachel Wilcox, DPT, MS Board-Certified Neurologic Clinical Specialist Learning Objectives Describe the main components of a neuron Classify the main types of neurons and neuroglial cells based on their associated functions D...

Cellular Overview PT 8203 - Neuroscience I Rachel Wilcox, DPT, MS Board-Certified Neurologic Clinical Specialist Learning Objectives Describe the main components of a neuron Classify the main types of neurons and neuroglial cells based on their associated functions Discuss the role of myelin in signal transmission and select clinical applications Describe action potential generation and information transmission Compare and contrast the roles of select neuromessengers Discuss the clinical implications of select agonists and antagonists Cellular Organization of Nervous System Two primary cell types Neurons Neurons/Nerve Cells Basic structural and functional unit Communicate with other neurons and cells in the body Receive & process input Generate output E.g. Electrical wire Neuroglia/Glial Cells https://www.123rf.com/clipart-vector/utility_pole.html “Nerve glue” Neuroglia Critical support network for neurons E.g. Utility poles, scaffolding, binding, maintenance crews Lundy-Ekman, Maring 2024 Neuron Structure Facilitates ability to receive, integrate, and transmit information Figure 5.1. Lundy- Ekman. Anatomy Review Process extending from soma, output site Dendrites for neuron End projection site of neuron; releases Synapse neurotransmitters into synaptic cleft Soma Branchlike extensions of cell body; main input sites for neuron Axon Site where neuron and postsynaptic cell communicate Axon hillock Tiny space located between presynaptic terminal and postsynaptic cell membrane Node of Ranvier Specialized region of soma from which axon arises Presynaptic terminal Interruption in the myelin sheath that Synaptic cleft leaves small patch of unmyelinated axon Cell body; contains organelles Lundy-Ekman Classification of Neurons Morphology Function Multipolar Afferent Bipolar Efferent Pseudounipolar Interneuron Image credit: Dr. R.C. Bohn Figure 5.1. Lundy-Ekman. Lundy-Ekman, Maring 2024 Morphological Classification of Neurons Multipolar (most common) Multiple dendrites from cell body + axon Shape and dendritic organization is variable based on function Examples: Lower motor neuron Purkinje fibers So many more! Figure 5.1A. Lundy-Ekman. Lundy-Ekman, Maring 2024 Morphological Classification of Neurons Bipolar Dendritic root + axon Examples: Retinal neurons Olfactory neurons Vestibular & auditory ganglia Figure 5.1A. Lundy-Ekman. Lundy-Ekman, Maring 2024 Morphological Classification of Neurons Pseudounipolar Two axon roots + no ”true” dendrites Peripheral: conducts information from periphery toward cell body Central: conducts information from cell body toward spinal cord Example: Somatosensory neurons Image credit: Dr. R.C. Bohn Figure 5.1A. Lundy-Ekman. Lundy-Ekman, Maring 2024 Functional Classification of Neurons Afferent Efferent ”Towards” or “inward” “Away from” or “outward” Single neuron Single neuron Towards soma (e.g. dendrites are Away from soma (e.g. axons are afferent processes) efferent processes) Nervous System Nervous System Neuron carries information Neuron carries information away towards CNS from CNS Can you think of an example? Can you think of an example? Motor neurons Sensory neurons Interneuron Process and convey information short distances E.g. spinal reflex arc Always in the CNS Lundy-Ekman, Maring 2024 Functional Classification of Neurons Afferent Interneuron Efferent Figure 5.1A. Lundy-Ekman Image credit: Dr. R.C. Bohn Lundy-Ekman, Maring 2024 Classification of Neuroglia Factors to consider Primary function: Myelinating Signaling/nourishing/cleaning Defending Location in the nervous system CNS PNS https://www.123rf.com/clipart-vector/utility_pole.html Lundy-Ekman, Maring 2024 Myelinating Neuroglia Form myelin: sheath of lipids and proteins that protects and insulates axon Oligodendrocytes Schwann cells Found in the CNS Found in the PNS Myelinates several axons Myelinates one part of axon (1:many) (many:1) https://www.youtube.com/watch?v=rwG0JXpW75Q https://www.youtube.com/watch?v=rwG0JXpW75Q Lundy-Ekman, Maring 2024  Role of Myelin Myelin prevents dissipation of electrical currents to allow for fast and efficient transmission of neural signals White matter: myelinated axons Gray matter: neuron cell bodies Nuclei or cortex: CNS Ganglia: PNS https://www.pinterest.com/pin/white-matter-and-grey-matter-brain-vs-spinal- cord--89157267601710964/ What effect would a demyelinating disease have on neural signal transmission? Slowing and/or complete disruption of the nerve impulse Lundy-Ekman, Maring 2024 Demyelinating Diseases Multiple Sclerosis Guillain-Barré Syndrome Destruction of oligodendrocytes Destruction of Schwann cells impedes conduction of electrical impedes conduction of electrical signals in CNS signals in PNS Figure 5.19. Lundy-Ekman Would you expect UMN or LMN signs? https://cpreplab.weebly.com/guillain-barreacute-syndrome.html Would you expect UMN or LMN signs? Lundy-Ekman, Maring 2024 Signaling/Nourishing/Cleaning Neuroglia Astrocytes Satellite cells Found in the CNS Found in the PNS Functions: Functions: Exchange signals with other Cover somas (cell bodies) neuroglia and neurons Regulate extracellular fluid of Regulate extracellular fluid of PNS CNS “Liaison” between neurons and blood capillaries Form critical component of blood brain barrier Figure 5.16A. Satellite cells. Lundy-Ekman. Figure 5.14. Astrocytes. Lundy-Ekman. Lundy-Ekman, Maring 2024 Defending Neuroglia Microglia Found in the CNS Function: As phagocytes, act as immune system of the CNS Prune nonfunctional cells and weak neuronal synapses during normal growth and development Remove debris from dying cells following stroke, traumatic brain injury, or infection https://www.ataxia.org/scasourceposts/snapshot-what-are-microglia/ Lundy-Ekman, Maring 2024 Clinical Correlate: Brain Tumors CNS tumors frequently originate from neuroglia Type Frequenc Origin Characteristics y Glioblastoma Most Astrocytes, More common in adults multiforme common oligodendrocytes, Found in cerebrum glial tumor and/or neural Malignant stem cells Astrocytoma 2nd most Astrocytes Found in brain or spinal cord common Grows aggressively Benign or malignant Oligodendroglio 3rd most Oligodendrocytes More common in adults, some ma common children affected https://www.braintumour.ca/ Found in frontal and parietal brain_tumour_types/glioblastoma- lobes gb/ Malignant Lundy-Ekman, Maring 2024 Knowledge Check Multipolar neurons are typically composed of: You are treating a patient with a Grade A. 1 dendritic root + 1 axon 2 glioblastoma multiforme brain tumor. Which of the following do you B. 2 axons + 0 dendrites expect to find during your physical C. Multiple dendrites + 1 axon therapy examination? A. Flaccid paralysis Which of the following is true of oligodendrocytes? B. Increased deep tendon reflexes (DTRs) D. Form a critical component of the blood brain barrier C. Absent pathological (primitive) E. Destroyed during acute episode of reflexes Guillain-Barré syndrome D. Fasciculations F. Can each myelinate several axons G. Act as the immune system of the CNS Transmission of Information Resting Membrane Potential Local Potentials Action Potentials Synaptic Events Figure 5.10. Lundy-Ekman. Resting Membrane Potential (RMP) Difference in electrical potential between the interior and exterior of neuron At rest, approximately -70mV Maintained via: Passive diffusion of ions through leak channels Na+/K+ pump Chunky anions (-) Figure 5.5. Lundy-Ekman. Lundy-Ekman Local Potentials Small(ish) change in membrane Two types: potential at receiving site of a Receptor: peripheral receptor of neuron sensory organ Can be depolarizing (+, excitatory) Stretch, compression, or hyperpolarizing (-, inhibitory) deformation, exposure to Proportional to size of the stimulus thermal/chemical agents Synaptic: postsynaptic membrane of motor or interneurons Binding of neurotransmitters Istoone local potential membrane enough of postsynaptic toneuron trigger an action potential? Depends on duration, amplitude, excitatory or inhibitory https://quizlet.com/385603339/mcn-ii-l6-wetzel-signalling-types-of-neuronal-electrical- signals-fig-21-pg-34-31-diagram/ Lundy-Ekman Summation Summation of depolarizing local Temporal potentials is critical for generation of action potentials! Temporal Several inputs, same location, rapid succession Spatial Several inputs, adjacent Spatial locations, simultaneously Figure 5.6. Lundy-Ekman. Lundy-Ekman Action Potentials (AP) Large depolarizing signal actively propagated along axon “All-or-none” threshold of -55mV A. RMP -70mV B. Summation of (excitatory) local potentials depolarizes neuron (inside more positive) C. Reaches -55mV, influx of Na+ leads to fast depolarization (inside even more positive) D. Efflux of K+ leads to repolarization (inside more negative) E. K+ channels remain open for hyperpolarization (inside even more negative) during refractory period; making it difficult to initiate another AP (inhibitory) Figure 5.6. Lundy-Ekman. Lundy-Ekman AP Propagation Unidirectional along axon towards Unmyelinated presynaptic terminal Speed of conduction increases with: Larger axon diameter Myelinated Greater amounts of myelin Saltatory conduction: AP “jumps” from one node of Ranvier to the next Figure 5.11. Lundy-Ekman. Will the AP conduct faster in the unmyelinated or myelinated axon? Lundy-Ekman Synaptic Events 1. AP arrives at presynaptic terminal 2. Membrane of presynaptic terminal depolarizes; Ca2+ channels open 3. Ca2+ triggers movement of synaptic vesicles  releasing neurotransmitters into synaptic cleft 4. Neurotransmitters diffuse https://qbi.uq.edu.au/brain-basics/brain/brain-physiology/action-potentials- and-synapses across synaptic cleft and bind to receptors 5. Postsynaptic potential (excitatory or inhibitory) is Maring 2024 generated Neuromessengers Neurotransmitters Neuromodulators Bind to and act directly on Released into extracellular fluid postsynaptic receptors to influence synaptic Actions can excite or inhibit to transmission determine postsynaptic Do not act directly on potential postsynaptic receptors Glutamate has excitatory Cortisol damages serotonin and effects dopamine receptor sites GABA has inhibitory effects Maring 2024 Postsynaptic Potentials Local synaptic potentials that occur due to change in ion concentration across the postsynaptic membrane Excitatory postsynaptic potential (EPSP): Depolarizing effect (becomes less negative) Facilitate AP generation Inhibitory postsynaptic potential (IPSP): Hyperpolarizing effect (becomes more negative) Inhibit AP generation Summation of EPSPs and IPSPs determines whether AP threshold is reached Maring 2024 Postsynaptic Potentials EPSP: Neuron is more excitable IPSP: Neuron is less excitable https://old-ib.bioninja.com.au/options/option-a-neurobiology-and/a5-neuropharmacology/synaptic-transmission.html Pharmacologic Agonists & Antagonists Agonist Mimics action of neurotransmitters Antagonists Blocks neurotransmitter from binding to specific receptor https://www.instagram.com/memorypharmstudy/p/Cifc5m-u9me/ Maring 2024 Clinical Correlates: Neurotransmitters Neuromesseng Site of Action Effect of Binding Agonists (+) and er Antagonists (-) Skeletal muscle Muscle contraction (-) Botulinum toxin membrane Acetylcholine ANS Parasympathetic actions (-) Atropine Brain Arousal, pleasure, reward (+) Nicotine Excitation, learning, and Glutamate Brain (-) Phencyclidine memory Inhibition, sedation, anti- (+) Alcohol, benzodiazepines, GABA CNS anxiety, antiseizure barbiturates, baclofen Emotion/ Reward seeking motivation (+) Amphetamines, cocaine, L- Dopamine system Dopa (-) Antipsychotic drugs Basal ganglia Movement control Regulate sleep, appetite, (+) Serotonin reuptake Serotonin CNS arousal, mood inhibitors (e.g. Prozac) Regulate wakefulness and Histamine Brain (-) Antihistamines Maring 2024 Let’s Practice! You are working with an Your patient takes an individual s/p CVA. antipsychotic medication for Is this an UMN or LMN injury? management of schizophrenia. UMN Is this a dopamine agonist or antagonist? Do we expect hyper or Dopamine antagonist hypotonicity in the involved extremities? Hypertonicity How might this medication impact the patient’s behavior and movement? Behavior: flat affect, poor motivation What effect would botulinum Impaired movement control – appear toxin injections have on the Parkinsonian (difficulty initiating involved Antagonistextremities? of ACh; block release at movement, small/stiff movements) neuromuscular junction, resulting in muscle relaxation Summary The human nervous system is primarily composed of multipolar neurons and neuroglial cells Neurons and neuroglial cells can be categorized based on their morphology, function, and/or location in the nervous system Myelin plays a vital role in propagation of fast and efficient neural transmission; dysfunction can lead to significant impairments in both the CNS and PNS Information is transmitted via generation of local potentials, action potentials, and synaptic release of neuromessengers Agonist and antagonist effects of pharmacologic agents on neurotransmitters have various implications for therapeutic management References Lundy-Ekman L. Neuroscience: Fundamentals for Rehabilitation (6th Edition). Elsevier Health Sciences. 2023. Maring J. Cellular Overview. Neuroscience I. PT 8203. The George Washington University, Spring 2024. Anatomy Review Process extending from soma, output site for neuron Dendrites End projection site of neuron; releases Synapse neurotransmitters into synaptic cleft Branchlike extensions of cell body; main Soma input sites for neuron Site where neuron and postsynaptic cell Axon communicate Tiny space located between presynaptic Axon hillock terminal and postsynaptic cell membrane Node of Ranvier Specialized region of soma from which axon arises Presynaptic terminal Interruption in the myelin sheath that leaves small patch of unmyelinated axon Synaptic cleft Cell body; contains organelles Lundy-Ekman