Lecture II. The Nervous System and Its Cells!

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Lecture II. The Nervous System Bio 3411! Friday! T. Woolsey! 3802 North Building 362-3601 woolseyt@wusm.wustl.edu! 2! 3! 4! Readings! Movie - vmjr-brain.mov! NEUROSCIENCE:!3 rd ed, pp 1-22! THE BRAIN ATLAS:!3 rd ed, pp 4-17! References:! Jellison et al (2004). Diffusion tensor imaging of cerebral white matter: a pictorial review of physics, fiber tract anatomy, and tumor imaging patterns. AJNR Am J Neuroradiol, 25:356-369! Ludwig, E., & Klingler, J. (1956). Atlas cerebri humani. Der innere Bau des Gehirns dargestellt auf Grund makroskopischer Praparate. The inner structure of the brain demonstrated on the basis of macroscopical preparations. Boston,: Little, Brown.! Ramón y Cajal, S. (1988). Recollections of my life. New York: Garland.!! (pdfs on course website: [http://artsci.wustl.edu/~sdanker/index.html])! 5! 6! 1!

Overview! A Few Facts! Main Features of Nervous System! Cells of Nervous System! Facts! Importance in Health and in Disease! 7! 8! Organ Weight!2-3% of body O 2 Consumption!20% of total Brain Energy (Glucose) Utilization!20% of total Brain Blood Flow!20% of heart output at rest! Elements Neurons (= nerve cells) 100 Billion Glia (= glue; supporting cells) 1 Trillion Synapses (= clasp) 1/1,000,000 th of all stars & planets in the universe/person [less than the total of human synapses in people living in the St.L area!!] Genes 50% of 20,000-25,000 genes in the human genome are expressed only in Brain [70% of the balance are also expressed in the nervous system; the total is 85% of the genome]! 9! 10! THE BRAIN ATLAS 3 rd ed, p. 8! Mid-line (sagittal) section through central nervous Features Brain, Spinal Cord, Other! system (CNS). Note the relationship between vertebrae (BLACK), segments of the spinal cord (RED) and spinal nerves (YELLOW).! 11! 12! 2!

THE BRAIN ATLAS 3 rd ed, p. 111! Peripheral (PNS - outside the skeleton) Magnetic Resonance Image (MRI) of head and neck at the midline.! "Sensory (sensation)!motor (movement)!!autonomic ( involuntary )!Enteric (gut) Central (CNS -inside the skeleton) "Spinal Cord (Spine)!Brain (Skull) 13! 14! THE BRAIN ATLAS 3 rd ed, p. 49! Views of the human spinal cord and lower brain stem.! LEFT - Left lateral (side) showing segments and spinal nerves.! MIDDLE - Anterior (front) view of spinal cord without showing enlargements.! RIGHT - Posterior (back) view of spinal cord with roots, ganglia and nerves.! Spinal Cord Segment! 15! 16! THE BRAIN ATLAS 3 rd ed, p. 20! THE BRAIN ATLAS 3 rd ed, p. 9! The different regions of the brain from the lateral (side) and median section (middle) human brain. These brain regions are discernable in in all vertebrates and in early embryos.! (cerebral cortex = gold; thalamus = blue/purple; midbrain = orange; pons = purple, cerebellum = blue; medulla = red/orange; spinal cord = green)! Left Lateral (side) view of the human Brain! 17! 18! 3!

THE BRAIN ATLAS 3 rd ed, p. 58! THE BRAIN ATLAS 3 rd ed, p. 59! 19! 20! THE BRAIN ATLAS 3 rd ed, p. 6! Components! Gray Matter" Cortex, Nuclei or Ganglia (groups of nerve cell bodies and neuropil) generally of similar function! Neuropil - neuronal processes, synapses and glia! 21! 22! Components! White Matter" Bundles (groups of myelinated axons [see below] that course in the same direction)! Tracts (also groups of axons (myelinated and un-myelinated but indicates origin, destination and therefore function)! 23! 24! 4!

Ludwig, E., & Klingler, J. (1956)! Jellison et al (2004)! Cerebrospinal Fluid (CSF)! The brain and spinal cord are bathed in a colorless fluid called cerebrospinal fluid (CSF). The fluid is made in chambers in the brain called ventricles (blue). It circulates between all the cells and their processes and in the space between a membrane on the brain surface (called the pia mater) and a membrane that is next to the skull or spine (arachnoid mater) called the subarachnoid space (gold).! 25! 26! Components! Movie - vmjr-brain.mov! Other" Blood Vessels (arteries, capillaries, veins and venous sinuses)! Coverings - meninges (dura mater (tough mother), arachnoid (spider web like), pia (tender/affectionate))! Cerebrospinal fluid (CSF - ventricles, canals, intercellular space, subarachnoid space)! 27! 28! Santiago Ramón y Cajal! (1851-1932)! Cells of Nervous System Neurons, Contacts, Support! ca. 1892! Cajal (say kaahaal) shared the 1906 Nobel Prize for discoveries indicating that the nervous system was made up of individual contiguous elements - the neurons.! 29! 30! 5!

Cells of Nervous System! Neurons" Parts: cell body (soma), dendrites (input processes), axon (output process)! Types: local circuit (90%), projection (10%)! Variations: stellate (star like); pyramidal (conical/ triangular); famous guys - Purkinje, Betz, Cajal, Retzius, Mauthner! All variations are correlated to particular functions.! 31! Photograph of neurons stained by Golgiʼs method which fills processes of some cells with black precipitates of heavy metals and Nissl which stains all nuclei and neuronal cytoplasm blue.! 32! Pyramidal neuron (conical cell body) stained by Golgiʼs method. There are multiple processes that resemble branches of trees (dendrites) and one that resembles a wire (axon; arrow). Inputs to the cell are mainly on dendrites and the cell body (soma) while outputs are mainly via the axon. This the principal long axon (output) cell in the cerebral cortex.! 33! Photograph of a Purkinje cell in the cerebellum stained by Golgiʼs method. The neuron has one complex dendrite that resembles a sea fan (arrow). Synapses on this cell type are estimated to be about 0.5 Million.! 34! Cells of Nervous System! Contacts (Synapses)! Parts: bouton or ending (contains vesicles (transmitters, modulators) and mitochondia), presynaptic membrane (dense in electron microscope); synaptic cleft; postynaptic membrane (dense in electron microscope)! Types: asymmetrical = Type I (postsynaptic membrane is thicker than presynaptic membrane; spherical clear vesicles) these are excitatory synapses - on; symmetrical = Type II (postsynaptic membrane same as presynaptic membrane; flattened clear vesicles) these are inhibitory synapses - off! Variations: large like to muscle, chalice in brain stem, climbing in the cerebellum; intermediate; small; in passing or as a terminal. All variations relate to specific functions (like variations in hammers - sledge vs. jewelerʼs).! 35! Photograph of the giant neuron in the brainstem of the gold fish (Mauthner) stained by Bodianʼs method. Synapses on this cell type are particularly easy to see. Much work on this cell type contributed to understanding the structure of the synapse before the electron microscope was perfected.! 36! 6!

Bio 3411! Most brain synapses (type I) have a wider cleft (space between the terminal and target process), thicker membrane densities on the terminal (pre) and process (post) and rounder vesicles. Such synapses are excitatory (on).! Electron micrograph of a synapse in the brain stained with the heavy metal element osmium (Os) which is lipophylic (stains lipids/fats). This synapse is only about 2 micrometers across.! About 10-20% brain synapses (type II) have a narrower cleft, thinner membrane densities on the terminal (pre) and process (post) and flat vesicles. Such synapses are inhibitory (off).! The main components of a synapse: synaptic cleft (space between the terminal and target process), membrane thickenings on the terminal (pre) and process (post), mitochondria and synaptic vseicles (contain transmitter(s)).! 37! 38! Cells of Nervous System! Glia (glue) or Supporting Cells" Parts: cell body (soma) and "short" processes! Types: astrocytes (star like); oligodendorcytes (fewer (oligo) branches (dendrites); microglia (small ones)! Variations: fleshy, fibrous (stringy), myelinating, non-myelinating! A neuron (red) grown in tissue-culture. Green shows proteins in processes from pre-synaptic neurons. The green/yellow dots on the red neuron indicate synapses. The inset shows a cartoon of blue synaptic terminals contacting a neuron. The picture gives a sense of the enormous numbers, distribution and density of synapses on a nerve cell. Neurons integrate information from thousands of synapses from many different sources.! 39! 40! NEUROSCIENCE (3rd ed, p.8, fig 1.5)! Cajalʼs drawing of glia in the spinal cord.! A Ependyma (lining of the central canal of the spinal cord)! All variations relate to specific functions.! B! C! A! B Oligodendrocytes which myelinate axons in fiber tracts! D! C Astrocytes - Protoplasmic! (fleshy)! in gray matter! D Astrocytes - Fibrous! Astrocyte! Oligodendrocyte! Microglial Cell! C! 41! 42! 7!

THE BRAIN ATLAS 3 rd ed, pp. 5, 7! How Does This Work?! Please vote on the following proposition: I think that the TA can run up the stairs to the back row of this auditorium in less than 10 seconds.! Yes! No! (Estimated elapsed time: )! 43! 44! Biology! Importance Biology, Disease! Understanding the brain is THE major question in biology and science.! Is it possible for the brain to understand itself?! The brain like any organ has functions: input, output, thought, communication.! 45! 46! Brain Diseases" Interfere with brain functions as heart disease interferes with the circulation.! Many diseases have a strong genetic component.! Prevalence is high: 15-30% of the population.! Cost is high: >> $2+ Trillion/year in care, lost income, social services, etc., in the US.! Impact (personal, family, societal) is persistent, pervasive, enormous, incalculable.! 47! 8!

What this lecture was about! Movie - vmjr-brain.mov! A Few Facts!!(genes, size, energy)! Main Features of Nervous System!!(brain, spinal cord, periphery)! Cells of Nervous System!!(neurons, glia, contacts)! Importance in Health and in Disease!!(bases, prevalence, impact)! 49! 50! 9!