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Neurobiology Syllabus: 1. A brief history of neuroscience. 2. Brain cells – neurons and glia. 3. Membrane equilibrium, Nernst potential. 4. Action potential, Hodgkin and Huxley model. 5. Cable theory. 6. Electrical and chemical synapses. 7. Integration in dendrites. 8. The taste system, the olfactory system, the somatic senses, muscle sense and kinesthesia, the sense of balance, hearing, vision. 9. Motor activity. Reflexes. Locomotion. Central pattern generators. 10. Communication and speech. 11. Specific transmitter systems. 12. Emotion. 13. Learning and memory. 14. The cerebral cortex and human behavior. Suggested reading list: G. Shepherd, Neurobiology E. Kandel, Principles of Neural Science D. Johnston i S. Wu Foudations of Cellular Neurophysiology P. Nunez, Electric fields of the brain. W.J. Freeman, Mass action in the nervous system. A.Longstaff, Neurobiologia. Krótkie wykłady, PWN G.G. Matthews, Neurobiologia. Od cząsteczek i komórek do układów, PZWL Edwin Smith Surgical Papyrus – 1700 BC (‘yś) - brain The Creation of Adam (1508-1512), Sistine Chapel, Vatican, Rome Meshberger, Frank Lynn. "An Interpretation of Michelangelo's Creation of Adam Based on Neuroanatomy", JAMA. 1990 Oct 10; 264(14):1837-41. Some steps in acquiring knowledge about the brain 4000 BC Euphoriant effect of poppy plant reported in Sumerian records 2700 BC Shen Nung originates acupuncture 3000 – 1700 BC Ancient Egypt. First written record about the nervous system. 2000 BC Skull trephination in the pre-Incan civilisations in South America 460-379 B.C. Hippocrates states that the brain controls sensations, emotions and movement and is the seat of intelligence 460-379 B.C. Hippocrates discusses epilepsy as a disturbance of the brain 387 B.C Plato believes that the brain is seat of mental process 335 B.C Aristotle believes heart is seat of mental process 130 – 200 AD Galen dissected brains (beginnings of the brain physiology). He also proposed four bodily fluids: blood, yellow bile, black bile, and phlegm. 1543 Andreas Vesalius publishes Tabulae Anatomicae - anatomy of the nervous system (and ribs!) The brain is the center of mind and emotion. 1673 Rene Descartes describes pineal gland as control center of body and mind 1792 Galvani discovers the electrical nature of the nervous activiy 1891 Cajal and others determine that the nervous system is composed of independent nerve cells 1897 Sherrington – nerve cells communicate with each other through synapses 1920s Langley, Loewi, Dale and others identify neurotransmitters 1940s Shannon, Weaver i Wiener introduce concepts of information processing and control systems (cybernetics). 1950s Hodgin, Huxley, Katz and Eccles – precise recordings of electrical signals with microelectrodes. 1950s Mountcastle, Lettvin, Hubel and Wisel – single cell analyses reveal ‘units of perception’ in the brain. 1960s Integrative functions of dendrites are recognized. 1970s Neuromodulator substances and second messangers are found 1970s Computer imaging techniques permit visualization of brain activity patterns in relation to sensation and cognition 1970s Molecullar methods are introduced for analyzing genetic mechanisms and single membrane proteins. 1980s Computer models of nervous system functions (vision, language, memory, logic) 1990s „The decade of the brain”: emphasis on combining information from different levels of analysis into integrated models of brain function and disease. 2000 and later Eric Kandel – understanding memory mechanisms Artificial brain: 1cm2 - Blue Brain Project Small mammal brain - C2 (IBM) Mammal Inteligence - MoNETA: A Mind Made from Memristors http://artificialretina.energy.gov/ Behavioural neuroscience: Rat navigation guided by remote control. Sanjiv K. Talwar, Shaohua Xu, Emerson S. Hawley, Shennan A. Weiss, Karen A. Moxon and John K. Chapin Nature 417, 37-38(2 May 2002) The levels of neuronal organization m o to r c entral sensory (b) Local populations, neuronal networks (b) Systems motor c ent ral sensory Dendrites + - + - + - + + + + - + - + - + (a) Behaviour Soma Axon (c) Single cells (f) Genes + + - + - + + + + - + - + + - (e) Membranes, channels, ions (d) Synapses The aim of neurobiology (and the course) Identifying the elementary units at different levels of organization of the nervous system and understanding the relations between different levels. Divisions of the nervous system The nervous system is divided into the central nervous system and peripheral nervous system. The central nervous system is divided into two parts: the brain and the spinal cord. The average adult human brain weighs 1.3 to 1.4 kg. The spinal cord is about 43 cm long in adult women and 45 cm long in adult men and weighs about 35-40 grams. The spinal cord is much shorter than the vertebral column. The peripheral nervous system consists of sensory division and motor division. Sensory division consists of peripheral nerve fibers that send sensory information to the central nervous system. Motor division consists of nerve fibers that project to motor organs. Motor division is divided into two major parts: the somatic nervous system and the autonomic nervous system. The somatic nervous system contains nerve fibers that project to skeletal muscle. The autonomic nervous system is divided into the sympathetic nervous system and the parasympathetic nervous system. Brainstem – pień mózgu Midbrain – śródmózgowie Pons – most Medulla oblongata – rdzeń przedłużony Cerebellum - móżdżek Diencephalon międzymózgowie Thalamus wzgórze Diencephalon międzymózgowie Hypothalamus podwzgórze Limbic system – system limbiczny Hippocampus hipokamp Lateral ventricle – komora boczna Basal Ganglia – zwoje podstawy Caudate – jądro ogoniaste Basal Ganglia – zwoje podstawy Caudate – jądro ogoniaste Putamen – skorupa Striatum – prążkowie = jądro ogoniaste + skorupa Amygdala – ciało migdałowate Cerebral Cortex – kora mózgowa White matter – isotota biała Frontal lobe – płat czołowy Temporal lobe – płat skroniowy Cerebral Cortex – kora mózgowa Grey matter – isotota szara Parietal lobe – płat ciemieniowy Occipital lobe – płat potyliczny The Neuron Doctrine Nerve cells in the cerebellum, as observed by Purkinje in 1837 A large motoneuron in the spinal cord, as observed by Deiters in 1865. Note the single axon (axis cylinder), dendrites and soma. The Neuron Doctrine Camillo Golgi (1843 - 1926) in his laboratory Golgiego stain made nowodays Based on large number of connections between neurons Golgi assumed that the laws of signals transmission cannot be specified and he proposed the reticular theory. Original Golgi stain The Neuron Doctrine Santiago Ramon y Cajal (1852 – 1934) Cajal developed the Golgi method and applied it to many parts of the nervous system in many animal species. He realized that the entitiy stained by the method is the entire nerve cell and he proposed that nervous system is composed of separate cells. Retina. Cajal’s drawing (1900) The Neuron Doctrine Wilhelm Waldeyer, a profesor of anatomy and pathology in Berlin published in 1891 a review in medical journal, stating that the cell theory applies to nervous system as well. He suggested the term ‘neuron’ for the nerve cell and the theory became known as the ‘neuron doctrine’ Heinrich Wilhelm von Waldeyer-Hartz (1836-1921) The Nobel Prize in Physiology or Medicine 1906 The Neuron Neuron types and size Unipolar neurons Bipolar neurons Axon diameter 0,004 mm - 100 microns (.1 mm) Hair diameter 0,02 mm do 0,08 mm. Multipolar neurons Axon length 1 mm - above 1 m In humans: About 1011 neurons in the brain Każdy neuron ok. 104 połączeń Average length of akson in the cortex 2 cm. Total length of axons A = 2*109 m Earth – Moon distance L = 4* 108 m A/L = 5 Neuron terminology Nerve cells which have long fiberst that connect to other regions of hte nervous system are called projection neurons, principal neurons or relay cells. Nerve cells which are contained wholly within one region of the nervous system are called intrinsic neurons or interneurons. Interneurons may not have an axon. Dendrites - terminology Neurons usually have a single axon and many dendrites. Dendrites may be apical or basal. The basal dendrites emerge from the base and the apical dendrites from the apex of the pyramidal cell body. Neuroglia (glia) Glial cells Glial cells are non-neuronal cells that provide support and protection for neurons. Neuroglial cells are generally smaller than neurons and outnumber them by five to ten times. Glial types and functions •Astrocytes: biggest and largest in number. They surround neurons and hold them in place. They supply nutrients and oxygen to neurons. They regulate chemical composition of extracellular space by removing excess ions, notably potassium. They regulate neurotransmission by recycling neurotransmitters released during synaptic transmission and by surrounding synapses and preventing diffusion of neurotransmitters. •Microglia: They destroy pathogens and remove dead neurons. • Oligodendrocytes: They coat axons in the CNS with their cell membrane forming a specialized membrane called myelin sheath. The myelin sheath provides insulation to the axon that allows electrical signals to propagate more efficiently •Schwann cells: Similar in function to oligodendrocytes, Schwann cells provide myelination to axons in the PNS. SM (sclerosis multiplex) - a disease in which oligodendrocytes are destroyed resulting in a thinning or complete loss of myelin causing neurons not to be able to effectively conduct electrical signals. Albert Einstein’s brain Einstein’s brain was removed within seven and a half hours of his death and was preserved for scientific studies. Einstein's brain weighed only 1,230 grams, which is less than the average adult male brain (about 1,400 grams). One of the differences that were found between Einstein’s brain compared to others was increased number of glial cells. It is known from animal studies that as we go from invertebrates to other animals and primates, as intelligence increases, so does the ratio of glial cells to neurons. It is hypothesized that glial cells (astrocytes) could communicate and transmit chemical signals throughout the brain. EEG measurement from Albert Einstein. Princeton, 1950