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NSCI 201 (15)
Chapter 1

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NSCI 201
Evan Balaban

Chapter 1 - Studying the Nervous System Overview • Neuroscience encompasses how the nervous system is organized, how they develop and how they generate behaviour • Genetics, genomics, molecular and cell biology, anatomy, systems physiology, behavioural observation and psychology help us find answers • Sensory systems tell the organism about its own state and the state of its environment • Motor systems deal with movement • Associational systems link the sensory and motor systems, and provide higher order functions like: perception, attention, cognition, emotions, language, thinking Genetics, Genomics, and the Brain • The brain is the product of gene expression • A gene is both: ◦ the coding DNA sequences (exons ) => the template for mRNA that will eventually be translated into protein ◦ the regulatory DNA sequences (promoters and introns) => control whether and in what quantities that gene is expressed in a given cell type • Genomics: a field that focuses on the analysis of complete DNA sequences (coding and regulatory) • The human genome contains approx. 20,000 genes ◦ 14,000 genes are expressed in the developing and/or mature brain ‣ 8,000 of these are in all cells and tissues ‣ Lots of brain-specific genetic info is in introns and regulatory sequences ◦ The diversity and complexity of brain function is due to the varying level and location of genes expressed in specific regions • Studying the genome helped us realize that some pathologies are due to the mutation of one or a few genes ◦ e.g. a mutation in a gene that regulates mitosis can = microcephaly Box 1A - Model Organisms in Neuroscience • The human brain is hard to study, so we turn to other organisms • We pick model species based on their assumed enhanced functional capacity (e.g. cats were studied since they are highly visual animals) • Studies on invertebrates (e.g. squids and Aplysia californica) gave us information about synaptic transmission, synaptic plasticity, and the cell biology of neurons ◦ They have very large nerve cells so were easy to study • Four model organisms have been chosen based on our ability to do genetic analysis and manipulation on them: ◦ Caenorhabditis elegans (C. elegans, a nematode) - 19,000 genes ◦ Drosophila melanogaster (fruit fly) - 15,000 genes ◦ Danio rerio (zebrafish) - 24,000 genes ◦ Mus musculus (mouse) - 25,000 genes • A majority of the genes in the above animals' genomes are expressed in their developing and adult brains • Advantages: we can do sophisticated genetic manipulations on them because we know a lot about their genomes ◦ Once we identify a gene for brain development, we can manipulate it in the model organisms ◦ Studying mutants of these animals allows to identify genes that change their phenotype ◦ Introducing genes into the genome or deleting (knocking out genes) makes transgenic animals, ◦ Homologous recombination: allows DNA constructs that disrupt or alter the expression of specific genes to be inserted into the location of the normal gene in the host species • Crayfish, lobster and insects have been useful for finding basic rules for neural circuit function • Avians and amphibians are useful for studying neural development • Mammals are useful for neuropharmacological and behavioural studies on the adult brain The Cellular Components of the Nervous System • Golgi thought there was one continuous nerve cell network => the "reticular theory" ◦ He identified the Golgi apparatus and developed the Golgi stain technique • The neuron doctrine, discovered by Cajal, overcame the reticular theory ◦ Neurons are discrete entities ◦ They communicate through synapses (coined by Sherrington) ‣ Some neurons communicate through gap junctions, which allow for direct electrical and chemical signals between cells • The cells of the nervous system are divided into 2 categories: ◦ Nerve cells (neurons) ‣ Specialized for electrical signalling over long distances ◦ Glial cells (neuroglia or glia) ‣ Support electrical signals ‣ Repair damaged neurons, act as stem cells in some regions (promote regrowth of damaged neurons) ‣ Can prevent the regeneration of neurons in some areas ◦ Both have: ‣ endoplasmic reticulum, Golgi apparatus, mitochondria, vesicular structures ‣ specialized fibrillar or tubular proteins that make up the cytoskeleton ◦ Neuron-specific organelle traits: ‣ concentrated mitochondria at synapses ‣ endoplasmic reticulum are not found at axons and dendrites Figure 1.4 • Microtubules are only found in the axons (which binds Tau) • Actin is localized to the tips of growing axons and dendrites • In epithelial cells, actin is in fibrils, which occupies most of the cell bodies • Actin is seen in fibrillar bundles in astroglial cells • Tubulin is found throughout the cell body and dendrites of neurons • The head of the spine of dendrites is enriched in actin, while the rest of it is made of tubulin • The cytoskeleton of non-neuronal cells is found as filaments of tubulin • There are proteins in the extracellular space between an axon and its target muscle Figure 1.2 Neurons • Specialized for intercellular communication and electrical signaling • Have extensive branching ◦ Axon ◦ Dendrites ‣ Arise from the neuronal cell body in the form of dendritic branches/processes ‣ Primary targets for synaptic input from axon terminals of other neurons ‣ Have lots of ribosomes • Some neurons have no dendrites (little innervation), others have many (lots of innervation) ◦ Number of inputs reflects the degree of convergence of a neuron ◦ Number of targets reflects the degree of divergence of a neuron ◦ Number of synaptic inputs received by each nerve cell is from 1 to 100,000 • Synaptic contacts are when the axon terminal of the presynaptic neuron is across from the postsynaptic rece
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