Lecture 011425 PDF

Lecture 011425 Readings: Course Description Ch 1, 2 – Lectures, Objectives, Exams and Grading – Moodle web site Divisions and Orientation – CNS and PNS – Planes of section Imaging – anatomical views: MRI, CT – functional views: PET, f-MRI C...

Lecture 011425 Readings: Course Description Ch 1, 2 – Lectures, Objectives, Exams and Grading – Moodle web site Divisions and Orientation – CNS and PNS – Planes of section Imaging – anatomical views: MRI, CT – functional views: PET, f-MRI Cells of the Nervous System Neurons Glial cells Case study – Multiple Sclerosis Course Information Moodle - use the META COURSE (1 site for all course listings lecture and lab) BIOL 4460 / 5560 01 / PT 5502, OT 5502 01 02: Clinical Neuroscience (JGroome), BIOL 4415L / 5515L Human Neurobiology Lab, Spring 2025. Syllabus, course description and link to recorded lectures in “General”. News Forum (Announcements) - Messages about posts and events. Weekly Posts Lectures. Power point as pdf file, posted prior to class period. Objectives. Goals for each module. Useful study guide – interactive is best! Each goal presents a set of vocabulary terms, relevant to that goal Each goal presents a set of concepts (synthesis of relevant information). Laboratories. Objectives, and Atlas Images for dissections. Useful as supplemental for lecture material in second module, Neuroanatomy. Reading quizzes. 10 total, 50 points, done on Moodle Web Site. Listed in Syllabus. Open book, due by class time on date posted in Syllabus. Missed RQ may be submitted as student generated RQ for 50% credit – during that module. Examinations - One exam per module. 100 points each. No cumulative final. - Remediation opportunity for Exam ONE only, up to 75%. Course Description Modules - One exam per module. Non-cumulative final = 4th midterm exam. – Neurobiology: Neurophysiology and Development – Neuroanatomy: Regional neuroanatomy and pathways. – Systems Neuroscience I: Sensory neurobiology, pathways. – Systems Neuroscience II: Motor and integrative neurobiology, pathways. Emphases – Mechanisms On to Module I – Pathways – Pathology – Case Studies  Basic Divisions of Nervous System Central Nervous System cerebrum thalamus midbrain pons, cerebellum medulla spinal cord “Brainstem” comprises the midbrain, pons and medulla. Peripheral Nervous System spinal nerves autonomic nerves Planes of Orientation Planes of Section posterior (dorsal) vs anterior (ventral) sagittal = (midline, longitudinal axis) rostral (front) vs caudal (rear) axial = horizontal (separates top to bottom) superior (above) vs inferior (below) coronal = perpendicular to long axis) “anterior” and “posterior” often used as “rostral” and “caudal, for structures in brain  Neural Imaging Computerized Tomography - CT scans X-ray beam rotated around patient, with detectors Tomography - several views of each “slice” (Scout) images taken at several planes assist in final Differing densities of air, blood, bone, brain computerized tomography  Contrast enhancement CT Typical CT scan (useful in head trauma, tumors, and hemorrhage) injection of contrast material (iodine) into femoral artery Hounsfield units of density air: -800 (black) fat: -80 water: 0 CSF: 10 brain matter: 35 blood: 75 CT myelography = spinal canal CT bone: 1200 (white) Typical and Contrast Enhanced CT scans Magnetic Resonance Imaging (useful in many clinical situations: cerebrovascular accident, tumors, neurodegenerative disease) 2 coils - change proton spin, then allow spin alterations to relax. Measure time to relaxation T2, T1 - T value differs based on tissue type T2 - horizontal spin relaxation T1 - vertical spin relaxation T2 T1 coronal axial T1 (best resolution) and T2 imaging (best contrast) images like CT, MRI can be used with other contrast enhancing techniques (axial scans) T1 T2 right left BOLD functional magnetic resonance imaging Lateral geniculate nucleus and Occipital Lobe (blood oxygen level dependent fMRI) - Vision oxy-hemoglobin and deoxy-hemoglobin differ magnetically (MRI). MORE oxy-hemoglobin to parts of brain receiving increased blood flow. Detect change in blood flow by change in image intensity. Used to study areas of brain active during sensory or motor tasks. Broca’s and Wernicke’s areas - language post central gyrus - somatosensory cortex Positron emission tomography (PET) introduce radioactively tagged substances into brain. detect g rays emitted at 180° measure changes in blood flow, changes in glucose metabolism label ligands for specific receptors Single photon emission computerized tomography (SPECT) greater diversity of isotopes to study more specific events, but less spatial resolution On to neurobiology Input Zone Neurons - functional morphology apical (distant) and basal (proximal) dendrites Neurophysiology – Module I soma (cell body) Dendritic Trigger Zone arbor axon hillock - spike initiation zone initial segment Propagation Zone axon myelin sheath Nodes of Ranvier collateral branches Output Zone axon terminal synaptic boutons containing vesicular NT  G Unipolar (A, D) (or) pseudo-unipolar (G) H Bipolar (B) Multipolar(H): Pyramidal (E) Purkinje (F) stellate granule Types of neurons - morphology  plasma membrane Neuronal Organelles signaling cytoskeletal elements transport architecture signaling nucleus with DNA genetic control center rough ER w/ ribosomes protein synthesis smooth ER modifications Golgi apparatus vesicles mitochondria metabolism Plasma membrane - electrical signaling of neurites Neurophysiology Dendritic arbor and spines – Module I Axon hillock and (myelinated) cable Axonal terminal and synaptic boutons Protein pumps for ion concentration gradients sodium potassium pump calcium pumps Ion channels for electrical gradients non-gated gated by specific stimuli Synaptic proteins for NT release and uptake Receptor proteins for transduction of signal ionotropic - ion channels metabotropic - biochemistry  Neuronal Transport Nucleus - codes for messenger RNA Rough ER - ribosomal synthesis of protein Smooth ER/Golgi - modification and packaging Microtubules and Neurofilaments - transport in cell body, neurites transport of organelles transport of vesicular neurotransmitter transport of enzymes Transmitters are synthesized in soma (i.e. peptides) OR Transmitters are synthesized at terminal (i.e. Ach) Neurofilaments Microtubules architectural cytoskeleton scaffold cytoskeleton intermediate 10 nm filaments axonal transport, cell division Microfilaments a / b tubulin polymers peripheral cytoskeleton GTP dependent polymerization cell-cell signaling small 3-5 nm filaments microtubule associated proteins dendritic MAP2 (shown at left) axonal tau, MAP3 MAPs regulate polymerization Axonal trafficking - microtubule based antero-grade, retro-grade cytoskeletal motors Visualizing transport axonal anterograde (towards terminal) transport - kinesin axonal retrograde (towards soma) transport - dynein * * * * Microglia Glial Cells resident tissue phagocytes (macrophages) responses to injury, infection scavenge necrotic debris Macroglia CNS macroglia: oligodendrocytes astrocytes PNS macroglia: Schwaan cells Gliosis - reactive proliferation Glial cell tumors astrocytoma glioblastoma multiforme oligodendrocytoma ependymoma schwannoma Glial Cell Functions Astrocytes: uptake of extra-cellular potassium uptake of released neurotransmitters contribute to blood brain barrier modulation of neuronal activity blood brain barrier Oligodendrocytes, Schwaan cells: production of myelin - saltatory conduction (O, S) framework and architectural support in CNS parenchyma framework for neuronal migration during development  Astrocytes most numerous glial cells end feet induce BBB in endothelial junctions important in K+ and NT uptake  Oligodendrocytes and Schwaan cells Central myelination Peripheral myelination - oligodendrocyte - Schwaan cell Glial cell membranes interrupted at Nodes of Ranvier - Na, K channels  Case study : Multiple Sclerosis A 28-year-old woman presented to her physician with complaints of weakness, numbness, and tingling in her left leg. Physical examination revealed moderate left weakness, more subtle weakness in the left leg, and loss of vibratory and position sense in both legs. A magnetic resonance imaging (MRI) scan of the head revealed abnormal signal in the peri-ventricular white matter. MRI of the spine revealed similar areas of signal abnormality within the spinal cord. She gradually improved over the next several months, and was fully ambulatory by 8 months after the initial episode. Approximately 2 years later, after an uneventful pregnancy, the patient experienced an abrupt loss of vision in her right eye. She was treated with corticosteroids, and her vision gradually improved over the next month, although a small visual field deficit persisted. At age 34, the patient developed a tremor, most noticeable when she attempted to pick things up. She also complained of feeling "clumsy" and, at times, had difficulty maintaining her balance. Over the next year, her tremor diminished, but she began to experience difficulty speaking (dysarthria), and suffered from several transient episodes of double vision (diplopia). Adapted from Robbins et al. 2005  Brain, multiple sclerosis - Magnetic resonance imaging (MRI) scan This MRI scan demonstrates areas of abnormal signal in the peri-ventricular white matter, suggestive of multiple sclerosis. Brain, multiple sclerosis – Gross, coronal section The white matter contains multiple areas of gray, gelatinous discoloration called plaques, corresponding to areas of de-myelination. The random distribution of plaques corresponds to the variable nature of the signs and symptoms that can be seen clinically in patients with multiple sclerosis. Adapted from Robbins et al. 2005  Brain, chronic multiple sclerosis plaque, Luxol fast blue (left) and Sevier-Munger (right) stains – High power These are highly magnified images of our patient's chronic MS plaque. Spinal cord, multiple sclerosis, myelin stain – Very low power This is a section of cervical spinal cord from a patient with chronic MS. With this stain, normal myelin appears black. Arrows indicate tracts compromised for several functions of patient. Can we correlate these lesions to symptoms? But of course…. Adapted from Robbins et al. 2005