Structure and functions of cells of the nervous system Chapter 2 Structure and functions of cells of the nervous system

Review Basic Genetics Sex Chromosomes and Sex-linked Traits Genes Chromosomes Made up of 4 nucleotide bases Adenine-thymine, guanine-cytosine Replication Duplication errors Sex Chromosomes and Sex-linked Traits Structural and Operator genes

Review Cells of the Nervous System Neurons Basic structure

Cells of the Nervous System Neurons Multipolar Unipolar Bipolar Glial cells Various types Provide a wide variety of supportive functions

Cells of the Nervous System Types of Neurons Multipolar Neuron – neuron with one axon and many dendrites attached to its soma; most common type in CNS. Figure 2.1

Cells of the Nervous System Figure 2.2 Types of Neurons Bipolar Neuron – neuron with one axon and one dendrite attached it its soma. sensory systems (vision and audition) Unipolar Neuron – neuron with one axon attached to its soma; the axon divides, with one branch receiving sensory information and the other sending the information into the central nervous system. somatosensory system (touch, pain, etc)

Copyright © 2006 by Allyn and Bacon

Figure 2.5 The Principal Internal Structures of a Multipolar Neuron

Inside the Cell Body From DNA (nucleus) to protein synthesis (cytoplasm) Transcriptional and translational processes take place in the cell body

Genetic Code and Genetic Expression Mechanism of gene expression Strand of DNA unravels Messenger RNA (mRNA) synthesized from DNA mRNA leaves nucleus and attaches to ribosome in the cell’s cytoplasm Ribosome synthesizes protein according to 3-base sequences (codons) of mRNA

Cells of the Nervous System Internal Structure Membrane – a structure consisting principally of lipid molecules that defines the outer boundaries of a cell and also constitutes many of the cells organelles, such as the Golgi apparatus Figure 2.20 Embedded in the membrane are a variety of proteins that have special functions---we’ll discuss some of these later

Cells of the Nervous System Internal Structure Cytoplasm – the viscous, semi-liquid substance contained in the interior of the cell; contains organelles Mitochondria – an organelle that is responsible for extracting energy from nutrients; ATP (adenosine triphosphate. Figure 2.5 Back to the rest of the cell…covered membrane and nucleus Bulk of the cell consists of cytoplasm

Cells of the Nervous System Internal Structure Endoplasmic Reticulum – parallel layers of membrane in the cytoplasm; stores and transports chemicals through the cell; 2 types Rough ER – contains ribosomes; produces proteins secreted by the cell Smooth ER – site of synthesis of lipids; provides channels for the segregation of molecules involved in various cellular processes

Cells of the Nervous System Internal Structure Golgi Apparatus – special form of smooth ER; some complex molecules are assembled here; also acts as a packaging plant, where products of a secretory cell are wrapped Exocytosis – the secretion of a substance by a cell through means of vesicles; the process by which neurotransmitters are secreted Lysosomes – an organelle containing enzymes that break down waste products; produced by Golgi apparatus. Exocytosis – container migrates to cell membrane, fuses with it and then bursts

Cells of the Nervous System Internal Structure Cytoskeleton – formed of microtubules and other protein fibers giving the cell its shape. Microtubule – a long strand of bundles of 13 protein filaments arranged around a hollow core; part of the cytoskeleton and involved in transporting substances from place to place within the cell. Axoplasmic Transport – active process by which substances are propelled along microtubules; 2 types Anterograde axoplasmic transport – movement from the soma to the terminal buttons; accomplished by kinesin and ATP; fast (500 mm/day) Retrograde axoplasmic transport – movement from the terminal buttons to the cell body; accomplished by dynein; about ½ as fast as antergrade transport Transport within a neuron -- Axons can be extremely long and sometimes the terminal buttons need items only produced in the cell body Need a way to get these items transported thru the axoplasm (cytoplasm of axons) Kinesis – protein molecule with ‘legs’

Cells of the Nervous System Supporting Cells Glia (glial cells) - Supporting cells that “glue” the nervous system together; 3 most important types are: Astrocytes Oligodendrocytes Microglia

Glial Cells Astrocytes – largest glia, many functions Myelin producers Oligodendrocytes (CNS) Schwann cells (PNS) Microglia – involved in response to injury or disease

Astrocytes Provide support to neurons Clean up debris phagocytosis. Provide nutrients and other substances Regulate chemical composition of the extracellular fluid Some of astrocyte’s processes are wrapped around blood vessels; other processes are wrapped around parts of neuron Astrocytes receive glucose from capillaries and break it down to lactate Lactate released into extracellular fluid and then taken up by neurons Astrocyte = star cell

Astrocytes and the Blood-Brain-Barrier ‘Selectively permeable’ Some substance can pass through the BBB BBB is not uniform Area postrema (medulla) Compromised Normal Figure 2.12

Glial Cells Oligodendrocytes Myelinate axons in the CNS Support axons and produce the myelin sheath A sheath that surrounds axons and insulates them, preventing messages from spreading between adjacent axons The sheath is not continuous (the bare portions are called nodes of Ranvier) A given oligodendrocyte produces up to 50 segments of myelin

Oligodendrocyte Figure 2.10

Glial Cells: Oligodendrocytes Myelin 80% lipid 20% protein Nodes of Ranvier 1-2 μm A given oligodendrocyte can give up to 50 coatings of myeline Figure 2.10

Glial Cells: Schwann Cells Peripheral cells Located in the PNS Can aid in the removal of dead or dying neurons Can then guide axonal sprouting CNS: axonal sprouts are hindered by glial scars (gliosis) A given oligodendrocyte can give up to 50 coatings of myeline Figure 2.11

Glial Cells: Microglia 10-20% of glial cells are microglia Cells originate in the periphery Phagocytosis- breakdown dying neurons, protect from invading microorganisms Primarily gray matter Hippocampus, olfactory telencephalon, basal ganglia, substantia nigra Phagocytosis

Microglia and Aging Reactive microglia present in aging rats 6 month 24 month Lucin and Wyss-Coray (2009) Reactive microglia present in aging rats Stress also shown to activate microglia

Microglia Activation and Alzheimer’s Disease Cagnin et al. (2001) The Lancet [11C]-PK11195: Peripheral BZP binding site present on activated microglia AD: entorhinal, temporoparietal, and cingulate cortex

The Cell Membrane Lipid bilayer Proteins embedded in the bilayer Selectively permeable to very few ions Proteins embedded in the bilayer Channel proteins Selective for ion type Receptor proteins Signalling devices The Cell Membrane

Neuronal Charge: Simple Design Measuring membrane voltage Requires: ONE recording electrode inside the cell (intracellular) ONE recording electrode outside the cell (extracellular) Figure 2.15

The Ionic Basis of the Resting Membrane Potential Membrane potential: The voltage across the neuronal membrane at any given time. Resting Membrane Potential: The voltage when a neuron is at rest (without synaptic input) At rest (RMP) -65 - -70 mV During an action potential -65 to +30 mV

Resting Membrane Potentials The RMP is entirely dependent upon The types of ions Where they are found (distribution across the membrane) It is because these ions are unequally distributed across the membrane, that the inside of the cell sits more negative in reference to the external environment. 65 mV

IONS Concentrations at Rest IONS OF INTEREST substance symbol -anions A– potassium K+ sodium Na+ chloride Cl– IONS Concentrations at Rest Uneven distribution of ions across the membrane

Ions of Interest: Resting Membrane Potential Figure 2.18

Membrane Potentials: The Pressures Membrane (lipid bilayer) is only selectively permeable to K+, Na+, Cl- (not permeable to A-) Figure 2.18

Membrane Potentials: The Pressures Figure 2.20 Two passive processes- Require NO energy One active process- Energy consuming

The Movement of Ions: Passive Processes 1) Diffusion Dissolved ions distribute evenly Ions flow down concentration gradient Diffusion of ions: Channels permeable to specific ions Concentration gradient across the membrane

The Movement of Ions: Passive Processes 2) Electrical (Electrostatic) Processes Opposite charges attract Like charges repel Attract Repel Cation Anion

The Movement of Ions: Active Processes Sodium-Potassium Transporter (also known as the Na+/K+ pump or Na+/K+-ATPase) Active mechanism in the membrane that extrudes 3 Na+ out and transports 2 K+ in. Figure 2.20

Channel Proteins (summarized) How Ions are Transferred Across the Membrane 1. Active 2. LEAK 3. Needs voltage to open (passive diffusion) 3. Voltage-Gated (open or closed) 1. Na+/K+-Pump 2. Non-Gated (always open)

An Action Potential Figure 2.17 Action potentials require a threshold level of depolarization to occur + + + 4

Action Potential Summary

An Action Potential Temporal and sequential importance of ion transfer across the membrane. Dependent on voltage-gated (dependent) channels Figure 2.21

Summary: Things to think about Membrane potentials Lipid bilayer Ion types (cations and anions contributing) Distribution of ions across the membrane Membrane proteins Channels Pumps/transporters: Passive vs active movement of ions Action potentials Threshold Temporal explanation of ion movement across the membrane.

Communication Within a Neuron Conduction of the Action Potential All-or-None Law – Principle that once the action potential begins, it proceeds without decrement to the terminal buttons. Figure 2.23 Studies have looked at conduction of action potential in giant squid axon…attach electrical stimulator to electrode at one end of axon and placed recording electrodes at different points along the axon

Communication Within a Neuron Conduction of the Action Potential Rate Law – principle that variations in the intensity of a stimulus or other information being transmitted in an axon are represented by variations in the rate at which that axon fires. Figure 2.24 If action potential is all or none how do we get variability …i.e., in the strength of a muscle contraction, the intensity of a stimulus A single action potential is not the basic element of information…info is represented by an axon’s rate of firing

Communication Within a Neuron Rate Law A single action potential is not the basic element of information Variable information is represented by an axon’s rate of firing A high rate of firing causes a strong muscular contraction Strong stimulus (bright light) casus a high rate of firing in axons of the eyes

Communication Within a Neuron Cable Properties – passive conduction of electrical current, in a decremental fashion, down an axon. Figure 2.25 APs are not the only kind of electrical signal that occur in neurons When a message is sent across synapse, a small electrical signal is produced in receiving neuron The transmission of weak subthreshold depolarizations is passive (no ion channels open or close)

Communication Within a Neuron Saltatory Conduction – conduction of action potentials by myelinated axons. The action potential appears to jump from one node of Ranvier to the next. No flow of Na+ Passive conductance until it reaches the nodes of Ranvier ….signal get smaller but still big enough to trigger AP at the node Figure 2.26

Factors Influencing Conduction Velocity Saltatory conduction High density of Na+ V-D at Nodes of Ranvier 2 advantages of Saltatory Conduction Economical Much less Na+ enters cell (only at nodes of Ranvier) mush less has to be pumped out. Speed Conduction of APs is faster in myelinated axons because the transmission between the nodes is very fast.

Communication Within a Neuron Multiple sclerosis Autoimmune degradation of myelin in PNS Without myelin the spread of + charge is diminished