Chapter 06 Lecture Outline See separate PowerPoint slides for all figures and tables pre- inserted into PowerPoint without notes. Copyright ©2017 McGraw-Hill Education. Permission required for reproduction or display. 1 Topics Section A Cells of the nervous Section C Synapses system 6.8 Functional anatomy of synapses 6.1 Structure and maintenance of 6.9 Mechanisms of neurotransmitter neurons release 6.2 Functional classes of neurons 6.10 Activation of the postsynaptic cell 6.3 Glial cells 6.11 Synaptic integration 6.4 Neural growth and regeneration 6.12 Synaptic strength Section B Membrane Potentials 6.13 Neurotransmitters and 6.5 Basic principles of electricity neuromodulators 6.6 The resting membrane potential 6.14 Neuroeffector communication 6.7 Graded potentials and action Section D Structure of the nervous potentials system 6.15 Central nervous system: Brain 6.16 Central nervous system: Spinal cord 6.17 Peripheral nervous system 6.18 Autonomic nervous system 6.19 Protective elements associated 2 with the brain The Nervous System • The Nervous System has two major divisions: – The Central Nervous System (CNS), which is composed of the brain and spinal cord. – The Peripheral Nervous System (PNS) is composed of the nerves that connect the brain or spinal cord with the body’s muscles, glands, and sense organs. • The neuron is the basic cell type of both systems. 3 Structure of a Neuron 4 Schwann Cells and Myelin • Schwann cells surround and form myelin sheaths around the larger nerve fibers. These are vital to regeneration and proper nerve signal conduction. 5 Myelination of Axons 6 Axonal Transport 7 Functional Classes of Neurons 8 Functional Classes of Neurons 9 10 Synapses Synapses can use both chemical and electrical stimuli to pass information. Synapses can also be inhibitory or excitatory depending on the signal/ neurotransmitter being transmitted. 11 Glial Cells 12 Glial Cells of the CNS • The glial cells in the CNS are: • Astrocytes: support cells, control extracellular environment of neurons • Microglia:”immune system” of the CNS • Ependymal cells: ciliated, involved with production of CSF and CSF movement • Oligodendrocytes: responsible for the myelin 13 Development of the Nervous System • Development of the nervous system in the embryo begins with stem cells that can develop into neurons or glial cells. • After the last cell division, each neuronal daughter cell differentiates, migrates to its final location, and sends out processes that will become its axon and dendrites. • A specialized enlargement, the growth cone, forms the tip of each extending axon and is involved in finding the correct route and final target for the process. • As the axon grows, it is guided along the surfaces of other cells, most commonly glial cells. 14 Development of the Nervous System • Which route the axon follows depends largely on attracting, supporting, deflecting, or inhibiting influences exerted by cell adhesion molecules and soluble neurotrophic factors (growth factors for neural tissue) in the extracellular fluid surrounding the growth cone or its distant target. • Once the target of the advancing growth cone is reached, synapses form. • During these early stages of neural development, which occur during all trimesters of pregnancy and into infancy, alcohol and other drugs, radiation, malnutrition, and viruses can exert effects that cause permanent damage to the developing fetal nervous system. 15 Development of the Nervous System • Early in development, the brain has much greater potential for remodeling in response to stimulation or injury than in the adult brain, a characteristic known as plasticity. • The basic shapes and locations of major neuronal circuits in the mature central nervous system do not change once formed. • The creation and removal of synaptic contacts begun during fetal development continue, however, though at a slow pace throughout life as part of normal growth, learning, and aging. 16 Injury of the Nervous System • If axons are severed, they can repair themselves and restore significant function provided that the damage occurs outside the central nervous system and does not affect the neuron’s cell body. • After such an injury, the axon segment that is separated from the cell body degenerates. The part of the axon still attached to the cell body then gives rise to a growth cone, which grows out to the effector organ so that function is sometimes restored. • Return of function following a peripheral nerve injury is delayed because axon regrowth proceeds at a rate of only 1 mm per day. 17 Injury of the Nervous System • Spinal injuries typically crush rather than cut the tissue, leaving the axons intact. • In this case, the problem is apoptosis of the oligodendrocytes. This results in loss of the myelin coat and the axons cannot transmit information effectively. • Severed axons within the CNS may grow small new extensions but no significant regeneration of the axon occurs across the damaged site, and there are no well-documented reports of significant return of function. 18 New Attempts to Repair Nervous System Damage • Researchers are trying a variety of ways to provide an environment that will support axonal regeneration in the central nervous system. – They are creating tubes to support regrowth of the severed axons, redirecting the axons to regions of the spinal cord that lack growth-inhibiting factors, preventing apoptosis of the oligodendrocytes so myelin can be maintained, and supplying neurotrophic factors that support recovery of the damaged tissue. • Medical researchers are also attempting to restore function to damaged or diseased brains by implanting stem cells, pieces of fetal brain or other brain tissues to replace the lost functions. 19 Basic Principles of Electricity 20 The Resting Membrane Potential 21 Membrane Potentials • Different cells have different resting membrane potentials. Neurons have a resting membrane potential generally in the range of –40 to –90 mV. • Changes in potential are due to movement of ions. • We can calculate the contributions of individual ions with the Goldman-Hodgkin-Katz (GHK) equation: The GHK equation is essentially an expanded version of the Nernst equation that takes into account individual ion permeabilities. 22 23 Resting Membrane Potential 24 Generation of a Membrane Potential Due to Diffusion of K+ 25 Generation of a Membrane Potential Due to Diffusion of Na+ 26 Forces Influencing Na+ and K+ at the Resting Membrane Potential 27 Establishing Membrane Potential • First, the action of the Na+/K+-ATPase pump sets up the concentration gradients for Na+ and K+. • Then there is a greater flux of K+ out of the cell than Na+ into the cell. This is because in a resting membrane there are a greater number of open K+ channels than there are Na+ channels. Because there is greater net efflux than influx of positive ions during this step, a significant negative membrane potential develops, with the value approaching that of the K+ equilibrium potential. • In the steady-state, the flux of ions across the membrane reaches a dynamic balance. Because the membrane potential is not equal to the equilibrium potential for either ion, there is a small but steady leak of Na+ into the cell and K+ out of the cell. • The concentration gradients do not dissipate over time, however, because ion movement by the Na+/K+-ATPase pump exactly balances the rate at which the ions leak through open channels. 28 Establishing the Resting Membrane Potential 29 Terminology • When talking about action potentials and graded potentials we use these terms: depolarization, repolarization, hyperpolarization. • These terms are all relative to the resting membrane potential (RMP). • Depolarization is the potential moving from RMP to less negative values. • Repolarization is the potential moving back to the RMP. • Hyperpolarization is the potential moving away from the RMP in a more negative direction. 30 Terminology 31 32 Graded Potentials • Graded potentials are changes in membrane potential that are confined to a relatively small region of the plasma membrane. • They are called graded potentials simply because the magnitude of the potential change can vary (is “graded”). • Graded potentials are given various names related to the location of the potential or the function they perform; for instance, receptor potential, synaptic potential, and pacemaker potential. 33 Graded Potential 34 Graded Potentials 35 Graded Potentials 36 Action Potentials • Action potentials are generally very rapid (as brief as 1–4 milliseconds) and may repeat at frequencies of several hundred per second. • The ability to generate action potentials is known as excitability. This ability is possessed by neurons, muscle cells and some other types of cells. • An action potential is a large change in membrane potential and is an “all or none” response. 37 Action Potential Membrane Depolarization • In order to cause an action potential, a cell must utilize several types of ion channels. • Ligand-gated channels and mechanically gated channels often serve as the initial stimulus for an action potential. • Voltage-gated channels give a membrane the ability to undergo action potentials by allowing the rapid depolarization and repolarization phases of the response. • There are dozens of different types of voltage-gated ion channels, varying by which ion they conduct (e.g., Na+, K+, Ca2+, or Cl-) and in how they behave as the membrane voltage changes. 38 Voltage-Gated Na+& K+ Channels 39 Mechanism of an Action Potential 40 Control Mechanisms of an Action Potential 41 Control Mechanisms of an Action Potential 42 Threshold and the All-or-none Principle 43 Clinical Effects of Action Potential Inhibition • The generation of action potentials is prevented by local anesthetics such as procaine (Novocaine®) and lidocaine (Xylocaine®) because these drugs block voltage-gated Na+ channels. • Without action potentials, graded signals generated in the periphery—in response to injury, for example—cannot reach the brain and give rise to the sensation of pain. • Some animals produce toxins that work by interfering with nerve conduction in the same way that local anesthetics do.