WHAT, THEN, IS THE BRAIN? The brain, perhaps the most complex system. What is the functional organization of the nervous system? 1. Reticular doctrine: Is the brain a reticular structure, a syncithium? NO 2. Neuron doctrine: The Neuron is the functional unit of the nervous system Camilo Golgi invented Golgi stain in the 1870's (19th century) Santiago Ramon Y Cajal
The neuron is a very specialized cell. It consists of: Body or soma, dendrites, axon, axon hillock, axon terminal, synaptic button Myelin is a fatty sheath that covers the axon. Node of Ranvier: gaps in the myelin Figure 2.5 Vertebrate motor neuron Node of Ranvier
Cells of the Nervous System Neurons and Glia Membrane: separates the inside of the cell from the outside Nucleus: contains the chromosomes Mitochondrion: useful for metabolic activities Ribosomes: sites for synthesizing new protein molecules Endoplasmic reticulum: network of thin tubes that transport synthesized proteins to other locations
Figure 2.3 The membrane of a neuronprotein channels permit certain ions to cross through the membrane Ion channels
Figure 2.2 An electron micrograph of parts of a neuron The nucleus, membrane, and other structures are characteristic of most animal cells. The plasma membrane is the border of the neuron.
The Structure of a Neuron Dendrites: branching fibers that get narrower as they extend from the cell body toward the periphery; information receiver Dendritic spines: short outgrowths that increase the surface area available for synapses Cell body :contains the nucleus and other structures found in most cells Axon: thin fiber of constant diameter, in most cases longer then the dendrites; information-sender Myelin: sheath-insulating material covering the axons; speed up communication in the neuron Presynaptic terminal: the point on the axon that releases chemicals
The brain has about 100 billion neurons and about 100 trillion connections between them Neurons can be classified according to: 1. Number of processes 2. Function: Unipolar Afferent (sensory) Bipolar Efferent (motor) Miltipolar Interneuron.
Figure 2.8 Cell structures and axonsIt all depends on the point of view. An axon from A to B is an efferent axon from A and an afferent axon to B.
Not all living systems have these three kinds of functional neurons. One-stage system (sensory-motor neuron): sea anemones (hydras) Two-stage system (sensory and motor neurons): jellyfish. Three-stage system (sensory-interneuron-motor): from mollusks (e.g., mussels) on.
GLIA: In addition to neurons, the brain is made of glial cells. Glial cells are about 10 times more numerous than neurons Functions of glia: 1. Structural support 2. Nutritive functions and general housekeeping functions 3. Help in forming the blood-brain barrier 4. guidance for neuron migration during development 5. Producing the insultain myelin for faster nervous conduction. Oligodendrocites in brain (central nervous system) Schwann cells in nerves (peripheral nervous system).
Macroglia: three kinds Oligodendrocites--produce myelin in Central NS Schawann cells-- produce myelin in Peripheral NS Astrocytes--participate in nutrition and blood-brain barrier
Figure 2.11 (a) Shapes of some glia cells.Oligodendrocytes produce myelin sheaths in the CNS. Each oligodendrocyte forms such segments for 30 to 50 axons. Schwann produce myelin in the PNS.Astrocytes pass chemicals back and forth between neurons and blood and among various neurons in an area. Microglia proliferate in areas of brain damage and remove toxic materials.
The Blood-Brain Barrier Why we need a blood-brain barrier? To keep out harmful substances such as viruses, bacteria, and harmful chemicals. (Neurons cannot divide). How the blood-brain barrier works? Endothelial cells are tightly joined to one another, and many molecules, including some drugs to fight cancer or Parkinson , cannot pass into the brain. What can pass the blood-brain barrier ? Passive Transport: requires no energy to pass Small uncharged molecules-oxygen and carbon dioxide Molecules that can dissolve in the fats of the capillary walls Active Transport: requires energy to pass Glucose, amino acids, vitamins and hormones
Figure 2.13 The blood-brain barrierMost large molecules and electrically charged molecules cannot cross from the blood to the brain. A few small uncharged molecules such as O2 and CO2 can cross; so can certain fat-soluble molecules. Active transport systems pump glucose and certain amino acids across the membrane.
Nourishment of Vertebrate Neurons Glucose-primary energy source for the brain Oxygen-needed to metabolize glucose Thiamine-necessary for the use of glucose
The Nerve Impulse The Resting Potential of the Neuron Resting potential: results from a difference in distribution of various ions between the inside and outside of the cell (-70mV inside compared with outside the cell) Measurement of the Resting Membrane Potential Microelectrodes Why a Resting Potential? Prepares neuron to respond rapidly to a stimulus
Figure 2.14 Methods for recording activity of a neuronDiagram of the apparatus and a sample recording.
Neurons are the functional units of the nervous system. What is the property that allows them to interact with each other? Neurons are capable of signaling Neurons communicate by sending electrical signals called Action Potentials Action Potentials are produced by the movement of ions in and out of the neuron, through the cell membrane. Ions are charged particles: Positive charges: cations Negative charges: anions
The Nerve Impulse What are the forces that move the ions across the cell membrane? Ions move along gradients of potential energy. What is potential energy? In the neuron, ions are moved by two forces (potential energy): Concentration Gradients: difference in distribution for various ions between the inside and outside of the membrane Electrical Gradient: the difference in positive and negative charges across the membrane
The cell membrane is a lipid bilayer which does not allow the passage of ions However, the membrane has protein channels that allow the passage of ions Protein channels are very selective
1. Concentration gradient Due to Concentration gradient between inside and oustside the membrane, K+, Na+, A-, Cl- ions tend to go: K+: OUT A- : OUT (large ions, proteins, RNA, DNA, etc, cannot leave) Na+:IN Cl-:IN
2. Electrical gradient Model of neuron: what happens if K+ channels open? Movement of K+ along a CONCENTRATION gradient creates an ELECTRICAL gradient. RESTING POTENTIAL: -70 mV (inside negative with respect to outside).
Figure 2.16 The sodium and potassium gradients for a resting membrane. Animation
What happens to Na+? CONCENTRATION & ELECTRICAL GRADIENTS PUSH NA+ IN !! What happens if Na+ channels open? AN ACTION POTENTIAL ! Momentary reversal of potential: positive inside, negative outside Na+ cannels closed Na+ channels open Outside ++++++++++ - - - - - - - - - - - membrane____________________________________________________ Inside - - - - - - - - - - - ++++++++++++ Resting Potential Action potential (-70 mV inside) (+50 mV inside)
The Action Potential Important Definitions Hyperpolarization: increasing the negative charge inside the neuron Depolarization: decreasing the negative charge inside the neuron Threshold of excitation: Level above which a stimulation produces a sudden depolarization of the membrane Action Potential: rapid depolarization and slight reversal of the usual polarization
Molecular Basis of the Action Potential Sodium channels open once threshold is reached causing an influx of sodium: depolarization to +50 mv Potassium channels open as the action potential approaches its peak allowing potassium to flow out of the cell: hyperpolarization to -70mv.
Fig 2.17 Sodium ions cross during the peak of the action potentialPotassium ions cross later in the opposite direction, returning the membrane resting potential
Why ion channels open or close? they are GATED by several stimuli: -electrical stimuli: differences in voltage: voltage gated. -chemical stimuli: chemical transmitters, (in synapses). -mechanical: for instance, the tap in the knee that produces the knee jerk reflex.
The Action Potential The All-or-None Law The size of an action potential (120 mv) and its speed are independent of the intensity of the stimulus that initiated it. Similar to firing a gun: when trigger reaches threshold, the bullet is fired with the same speed no matter how strongly the trigger is pulled.
The Action Potential The Refractory Period: after an action potential, the neuron resists the production of further action potentials Two Refractory Periods 1. Absolute Refractory Period (1-2 msec) The sodium gates are firmly closed The membrane cannot produce an action potential, regardless of the stimulation. -Limits the maximum firing frequency: 1000/sec -Action potential cannot reverse direction 2. Relative Refractory Period A stronger than normal stimulus can result in an action potential.
CHARACTERISTICS OF THEACTION POTENTIAL -Na+ and K+ channels in axon are voltage gated. -Action Potential aretriggered by positive change in membrane potential. -Threshold potential: 10 mV (from -70 mV to -60 mV) -Size of action potential:120 mV: from -70 mV to + 50 mV (all or nothing) -Action potentials are triggered in the axon hillock. No action potentials in soma or dendrites (but new data suggest otherwise)
The first ionic event in the generation of an action potential is the opening of Na+ channels Duration of Action Potential: about 1 msec The action potential ends because -The gate for Na+ closes, -The gates for K+ opens: outflow of K+, accumulates + charges outside, bringing the potential inside back to -70 mV. -Inflow of Cl- attracted by the + charges inside (gates for Cl- are always open).
Propagation of the Action Potential Axon Hillock-where the action potential begins Terminal Buttons-the end point for the action potential The action potential flows toward the terminal and does not reverse directions because the area where the action potential just came from are still in refractory period
Propagation of Action Potential Passive membrane properties The propagation of action potential is mediated by voltage-gated channels. A potential at one place triggers the neighboring place (domino effect) Homology with the burning of a flame down a wick. Heat-gated channel. A flame, like the action potential, cannot go back.
The Myelin Sheath and Saltatory Conduction Speed of conduction Saltatory conduction. By isolating a segment of the axon, myelin forces the action potential to jump from one node of Ranvier to the next. Na+ channels accumulate in the nodes of Ranvier In large myelinated axons, the conduction can be as much as 100 m/sec, or 220 miles per hour. The propagation speed is slower in small, unmyelinated fibers. Myelosclerosis, multiple sclerosis: slow down or stop conduction
Figure 2.20 Saltatory conduction in a myelinated axonAn action potential at the node triggers flow of current to the next node, where the membrane regenerates the action potential.
Effect of action potentials on the concentration of ions inside the cell is Very small. There is a Na+-K+ pump that kicks Na+ out and brings K+ in to maintain the concentrations at a stable value. This pump requires metabolic energy (ATP). After blockade of the Na+-K+ pump (with DNP, dinitrophenol), there can be thousands of action potentials.
Mechanisms of action of local and general anesthetics & venoms: Local anesthetics (Novocain, xylocaine) attach to Na+ channels, preventing Na+ inflow General anesthetics (ether, chloroform) Open K+ channels: clamp potential Scorpion Venom: Keeps Na+ channels open and K+ channels closed Tetrodotoxin (TTX, from puffer fish) blocks Na+ channels Cyanide blocks ATP-dependent Na+-K+ pump