Chapter 1: Studying The Nervous System PDF

Chapter 1: Studying the Nervous System Introduction to the Nervous System -​ The nervous system is composed of two main types of cells: neurons and glial cells -​ These cells form the foundation of all nervous system functions, from transmitting signals to providing support Neurons:...

Chapter 1: Studying the Nervous System Introduction to the Nervous System -​ The nervous system is composed of two main types of cells: neurons and glial cells -​ These cells form the foundation of all nervous system functions, from transmitting signals to providing support Neurons: The Primary Signaling Units 1.​ Structure of Neurons: -​ Dendrites: -​ Highly branched extensions of the cell body -​ Specialized for receiving signals from other neurons -​ Contains neurotransmitter receptors -​ Cell Body (Soma): -​ Contains the nucleus and is the site of protein synthesis -​ Houses organelles such as mitochondria and endoplasmic reticulum for metabolic activities -​ Axon: -​ A single, long extension that transmits action potentials to other neurons or target cells -​ Can be myelinated or unmyelinated -​ Axons vary in length; some span a few micrometers, while others extend over a meter -​ Myelin Sheath: -​ Insulates axons, allowing faster signal transmission -​ Produced by: -​ Oligodendrocytes in the CNS -​ Schwann cells in the PNS -​ Nodes of Ranvier: -​ Unmyelinated region of axon -​ Gaps in the myelin sheath where ion channels are concentrated -​ Facilitate saltatory conduction, enabling rapid signal propagation 2.​ Synapses: -​ The site where two neurons communicate -​ Involves: -​ Presynaptic terminal (terminal bouton): Releases neurotransmitters stored in vesicles -​ Synaptic cleft: The space between neurons where neurotransmitters diffuse -​ Postsynaptic terminal: Contains receptors that bind neurotransmitters -​ Typically a neuron, but not always - ex. Neuromuscular junction  3.​ Polarization and Signal Transmission: -​ Neurons are highly polarized, with distinct regions for input (dendrites) and output (axon terminals) -​ Proteins and organelles are trafficked along the axon via microtubules using molecular motors 4.​ Types of Neuronal Connections: -​ Divergence: Few presynaptic neurons communicate with multiple postsynaptic neurons -​ Convergence: Multiple presynaptic neurons synapse onto a single postsynaptic neuron Glial Cells: Supportive and Functional Units Types of Glial Cells in the CNS: 1.​ Astrocytes: -​ Maintain the blood-brain barrier -​ Regulate ion and neurotransmitter concentrations -​ Secrete chemicals essential for synaptogenesis (release of neurotransmitters) -​ Star-like structure 2.​ Oligodendrocytes: -​ Myelinate axons in the CNS -​ Each oligodendrocyte can myelinate multiple axons 3.​ Microglia: -​ Act as the immune cells of the CNS -​ Perform phagocytosis to remove debris and secrete cytokines during injury Types of Glial Cells in the PNS: 4.​ Schwann Cells: -​ Myelinate axons in the PNS (one Schwann cell per axon segment) -​ Aid in nerve repair and regeneration after injury Neural Circuits: Components: -​ Afferent Neurons: Carry sensory information toward the CNS -​ Efferent Neurons: Transmit motor commands away from the CNS -​ Interneurons: Facilitate local processing within circuits, often with short axons -​ Neuropil: A dense region of interwoven neuronal and glial processes where synaptic connections occur  -​ Signal types: excitatory, inhibitory, modulatory (depends on type of neurotransmitter released) Neural circuit example - knee-jerk reflex: 1.​ Hammer tap stretches tendon, which stretches sensory receptors in the leg extensor muscle -​ Sensory neuron receptor detects hammer tap 2.​ Sensory (afferent) axon synapses with and excites motor (efferent) neuron in spinal cord 3.​ Sensory neuron excites spinal interneuron 4.​ Interneuron synapse inhibits motor neuron to flexor muscles, allowing relaxation 5.​ Motor neuron conducts an action potential on extensor muscle fibers, enabling contraction 6.​ Flexor muscle relaxes because the activity of its motor neurons has been inhibited 7.​ Leg extends Patterns and timing of action potentials during myotatic knee-jerk reflex: -​ Sensory neuron: many action potentials, decreases before extension -​ Depolarization, repolarization, hyperpolarization -​ Motor neuron (extensor): eventual increase in A.P. -​ Depolarization, repolarization -​ Interneuron: eventual increase in A.P. -​ Depolarization, repolarization -​ Motor neuron (flexor): inhibited by interneuron synapse -​ hyperpolarization Techniques for Studying Neural Activity: 1.​ Calcium Imaging: -​ Calcium-sensitive dyes are used to monitor neuronal activity -​ Process: -​ Part of the skull is removed to expose the monocular region of brain -​ A microscope tracks changes in calcium release, which correlate with neuronal activation -​ Applications: -​ Observing neuronal responses to visual stimuli, with different neurons activated based on stimulus orientation.  2.​ Optogenetics: -​ A method to control neuronal activity using light-sensitive proteins called opsins -​ Process: -​ Genes encoding opsins are introduced into neurons -​ Opsin proteins are used to manipulate neuronal activity with light Light activated cation channels (Channelrhodopsins): -​ Blue light opens channels allowing positively charged ions to flow into neurons -​ Trigger action potentials when exposed to blue light -​ Influx of ions depolarizes neuron, firing an action potential -​ Used to stimulate specific neurons Light activated chloride transporters (Halorhodopsins): -​ Green light pumps chloride ions into the neuron -​ Influx of negatively charged ions makes neuron more negatively charged, leading to hyperpolarization -​ Hyperpolarizes neurons, preventing action potentials -​ Used to inhibit specific neurons -​ Applications: -​ Precise control of neural circuits to study behavior and brain function -​ Optogenetic probes can enable or inhibit action potentials in different parts of the brain, causing different functions -​ Ex. striatum, substantia nigra Structural analysis of neural systems: -​ Lesion studies: damaging/observing specific areas of the brain to understand their roles to determine direction of information flow Labeling proteins: -​ Transgenic reporters: genetically engineered organisms that express a reporter gene under control of gene promoters -​ Used to study activity of specific genes and visualize where they are expressed -​ Antibody labeling: uses antibodies that specifically bond to proteins of interest -​ Used to detect and localize proteins and study their distribution, interactions, and abundance -​ In situ hybridization: detects and localizes mRNA molecules for specific proteins -​ Involves binding/hybridization of an mRNA with the cDNA for a particular protein, where the sample can then be visualized -​ Used to study gene expression by identifying the location of mRNAs, and indicates where proteins will be synthesized Organization of the Nervous System  1.​ Central Nervous System (CNS): -​ Composed of the brain and spinal cord -​ Responsible for processing sensory input and generating motor output 2.​ Peripheral Nervous System (PNS): -​ Extends the CNS into the body -​ Includes sensory and motor pathways that connect to peripheral organs Order of signal direction: Internal and external environment → sensory components → central nervous system → → motor components → effectors The genome and Neural Systems Genomics: analysis of the complete DNA sequence of a species or individual Role of the Genome: -​ The human genome contains genes that regulate brain organization and function -​ Approximately 84% of human genes are expressed in the nervous system, and 30% are expressed exclusively in the brain -​ Single-gene mutations (gene ASPM) can have profound effects on brain development Model organisms + number of genes: -​ Human (20,000) -​ Mouse (25,000) -​ Zebrafish (24,000) -​ Fruit fly (15,000) -​ Nematode (19,000) Genetic Engineering Techniques: 1.​ Knock-in/Knock-out Models: -​ Insert or remove specific genes in model organisms to study their roles 2.​ Cre-LoxP System: -​ manipulates/disrupts specific DNA sequences in a controlled manner -​ Typically used in mice -​ Uses promoters to control gene expression in specific tissues Components:  -​ Cre recombinase: site specific enzyme that recognizes and acts on specific DNA sequences called loxP sites -​ Removes floxed exon from loxP sites, disrupting gene function -​ loxP sites: DNA sequence that Cre recombinase binds to and catalyzes DNA recombination -​ Floxed gene: loxP binding sites are inserted around a critical exon In most cells: -​ Cre recombinase is not expressed because the promoter controlling it (nestin promoter) is not active -​ The floxed gene remains intact and functional In nervous system cells: -​ The nestin promoter drives the expression of Cre recombinase -​ Cre recombinase removes exon 2 of the androgen receptor gene, disrupting the gene in cells where the nestin promoter is active Effect: -​ The targeted gene (androgen receptor) is disrupted only in nervous system cells, where Cre recombinase is expressed -​ This leads to the loss of the gene’s function in those cells 3.​ CRISPR-Cas9 system: -​ A precise gene-editing tool used to modify specific DNA regions by introducing double-stranded breaks Components: -​ Cas9 (endonuclease): a protein that introduces a double-stranded break in DNA -​ Guide RNA (gRNA): Directs Cas9 to the target sequence -​ One end of gRNA recognizes the endonuclease Cas9, while the other hybridizes with the complementary DNA region to guide Cas9 to the target Process: 1.​ Introduction of the CRISPR-Cas9 system: -​ gRNA complex is introduced into the cell 2.​ Targeting and cleavage: -​ gRNA directs Cas9 to the specific DNA region -​ Cas9 binds to the target DNA and creates a double-stranded break at the specific location 3.​ Repair mechanisms: -​ Simple repair mechanism: -​ Naturally occurring mechanism  -​ A few base pairs are added or deleted, resulting in a frame-shift mutation -​ This disables the protein, producing a gene knockout (loss of function) -​ Can introduce unintended mutations -​ Homology-directed repair: -​ Requires a template DNA fragment for precise recombination -​ Allows for insertion of new DNA sequences -​ Can introduce diseased allele, correct mutations, and introduce specific genetic modifications Effect: -​ Can induce mutations, insertions, or deletions, allowing detailed study of gene function -​ Can be used to create animal models of certain diseases to study disease mechanisms and test drugs