BASIC NEUROSCIENCE SERIES: INTRODUCTION AND SERIES OVERVIEW Sindhu Ramchandren, MD, MS AN OVERVIEW OF BASIC NEUROSCIENCE ..Or, How the knowledge of some esoteric anatomic, cellular or signaling process may help you treat a patient What is Neuroscience? • A scientific study of how the Nervous system (CNS and PNS) carries out its function • What are the Nervous System’s functions? • The Nervous System directs an individual’s ‘normal interactions’ with external stimuli • Thus, the Nervous System includes all thoughts, perceptions, bodily actions, behaviors, and ultimately: Consciousness • Philosophical debate: • Dualism: • Mind and Body are separate; “mind” is distinct from “brain” • Rene Descartes (1596-1650): “soul” controlled muscles via the pineal gland by hydraulic mechanisms • Monism: • Mind/brain is the nervous system • Rapidly gained acceptance among neuroscientists, facilitated by discovering electricity in the 18th century (Ben Franklin, Luigi Galvani) Evolution of the brain • The Human Brain has evolved from the inside out • Lower regions like the brainstem are generally more ancient than higher regions, such as the frontal cortex. • Basic survival functions like breathing are controlled in the lower brainstem • The large prefrontal cortex in humans is a late evolution Localization based on: • Symptoms: what the patient experiences • Signs: What the examiner observes • Helpful information: Timing (acute, subacute, chronic) Progression (static, step-wise regression, relapsing-remitting; progressive) Basic Neuroscience can help.. • Interpret the clinical manifestations in physiologic terms • Suggest treatments What is the brain made of? • Cells - distinct, individual cells, or networks of fused cells (syncytium, reticulum)? • Debated by Camilo Golgi; Santiago Ramón y Cajal, etc. • Methods: 1. Nissl and other traditional stains 2. Golgi method 3. Fluorescence labelling 4. Electron microscopy • Cell types: neurons, glia, capillary endothelial cells Building blocks • Neurons: Responsible for information • • • • • transmission throughout the Nervous system Cell body: contains nucleus and other biologic essentials to keep cell alive Dendrites: fibers that project out of the cell body, receiving info from other neurons Axon: transmits signals through the neuron Axon terminals: end of the axon; send messages to a different neuron Glial Cells: Support neurons by disposing waste products, stabilizing chemical environment, insulating neurons Signaling • Communication within a neuron is electrical • • Axon- akin to the copper wire; damage- see dimunition of size (amplitude) Myelin (oligodendrocytes in CNS; Schwann cells in PNS)- akin to the insulation; damage- see loss of speed (conduction velocity) • Communication between neurons is chemical • Neurotransmitters • Agonists: drugs that increase the activity of neurotransmitters • Antagonists: drugs that decrease the activity of neurotransmitters Peripheral Nervous System and disease states A. Motor neuron: • A B. B C. C D. D E E. MND Nerve root: • Radiculopathy Peripheral nerve: • Neuropathy Neuromuscular junction: • MG/ LEMS/ Botulism Muscle • Myopathy Disease States Cellular/genetic • Cortical excitability: epilepsy • Cellular dropout: Basal ganglia degenerative disorders • Neuromuscular junction blockade: Myasthenia gravis, LEMS, Botulism • Schwann Cell mutation: CharcotMarie-Tooth disease (CMT, or inherited neuropathy) Anatomic • Anton’s syndrome (visual anasagnosia, or cortical blindness): bilateral occipital cortex lesion • Alexia without Agraphia: (can write, but can’t read; not even what they wrote): Left occipital cortex lesion • Gerstmann’s syndrome: Agraphia, acalculia, finger agnosia, left-right confusion: Left angular gyrus lesion Heuristic: case-series based • Patient HM • intractable epilepsy (perhaps due to bike accident at age 9) • underwent surgery to remove hippocampus at age 27 • left him profoundly amnesic • Patient Phineas Gage • Large iron rod destroyed his left frontal lobe • Profound changes in behavior and loss of social cues • The Man who mistook his wife for a hat (Oliver Sacks) • Prosopagnosia, visual agnosia • The phantom within (Ramachandran and Blakeslee) • Phantom limb pain; mirror neurons and neural plasticity How principles of Basic Neuroscience help us treat patients • Brain scans- neurons require O2 and other nutrients to function • PET scans use a dose of radioactive glucose, which moves to the more-active areas of the brain • fMRI detects active areas of the brain by enhancing those areas that require more O2 • Neurophysiology: • EMG/NCS: patchy slowing of conduction in several nerves can help diagnose Chronic Inflammatory Demyelinating Polyneuropathy or its variants • EEG: If the differential of an obtunded patient is non-convulsive status vs. metabolic encephalopathy, EEG showing Theta slowing with triphasic waves can help support metabolic/hepatic coma • Neurotransmitters: • Allow us to manipulate disease states with appropriate uses of agonists and antagonists. Organization of Basic Neuroscience Series Three “cores” 1. Basic science ‘Anatomy’ • Embryology and cell type organization • Cell types by specific sites (cerebral cortex, brain stem, spinal cord, etc.) 2. Physiology (normal) • Cellular signaling • Sensory integration (vision, balance, sensation, etc.) 3. Physiology (disease) • Specific disease states (not clinical care for them, but what went wrong cellularly/mechanistically to result in the disease) Last lecture of the year: “Physiology of Consciousness” By Dr. George Mashour Online “course” • Online Neuroscience Course Link: http://neuroscience. uth.tmc.edu/toc.htm Example: Retinal Circuit with Lateral Inhibition Resulting in Edge Enhancement From: http://neuroscience.uth.tmc.edu/toc.htm Expectations • What this course will emphasize: • Overview of basic physiology, cell types, and signaling • Overview of multiple ways the above can fail, leading to disease states • What it can’t do: • Clinical overview- Dr. Callaghan’s Series will cover those, BUT we have tried to ensure that most topics are being presented by clinicians • Pathology overview- We cannot do a whole overview of CNS/PNS pathology and also do what the Department has charged us with teaching you through this series, BUT we do have a few lectures sprinkled in Most importantly: • These will be available at the end of each upcoming lecture; please provide your feedback anonymously and I will review the responses • If there are themes that become apparent in the feedback, I will make sure that subsequent lecturers are aware of what works and what doesn’t, so they can modify their talks (rather than waiting for end-of-year feedback only) • This only works if you ATTEND the lecture and fill out the responses! Discussion • Beginning-of-year evaluation: expectations • Will repeat these at end-of-year, to make sure we achieved the goals we set • Any other thoughts or comments on ensuring a good learning experience?