Human Anatomy & Physiology PDF

Human Anatomy & Physiology Second Edition Chapter 11 Introduction to the Nervous System and...

Human Anatomy & Physiology Second Edition Chapter 11 Introduction to the Nervous System and Nervous Tissue PowerPoint® Lectures created by Suzanne Pundt, University of Texas at Tyler Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved  MODULE 11.1 OVERVIEW OF THE NERVOUS SYSTEM Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Overview of the Nervous System Nervous system – controls perception and experience of world – Directs voluntary movement – Seat of consciousness, personality, learning, and memory – Regulates many aspects of homeostasis with endocrine system:  respiratory rate  blood pressure  body temperature  sleep/wake cycle  blood pH Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Anatomical Divisions of the Nervous System Divided anatomically into central nervous system (CNS) and peripheral nervous system (PNS) (Figure 11.1): – CNS – brain and spinal cord  Brain – billions of nerve cells (neurons); protected by bones of skull  Spinal cord – begins at foramen magnum; continues through vertebral foramina of first cervical to first or second lumbar vertebra – Millions of neurons; much fewer than brain/ Enables brain to communicate with most of body below head and neck – PNS – all nerves in body outside protection of skull and vertebral column  Nerves – axons of neurons bundled together with blood vessels and connective tissue; carry signals to and from CNS; classified by origin or destination – Cranial nerves – 12 pairs of nerves traveling to or from brain – Spinal nerves – 31 pairs of nerves traveling to or from spinal cord Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Anatomical Divisions of the Nervous System Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Functional Divisions of the Nervous System Nervous system functional categories: sensory, integrative, or motor: – Sensory – sensory (afferent) division of PNS gathers information about internal and external environments; input from both subdivisions (below) carried from receptors to spinal cord and/or brain by spinal and cranial nerves  Somatic sensory division (special sensory division) –carry signals from skeletal muscles, bones, joints, and skin; also, from organs of vision, hearing, taste, smell, and balance  Visceral sensory division – transmit signals from viscera (heart, lungs, stomach, kidneys, and urinary bladder) – Integrative functions – analyze and interpret incoming sensory information; determine an appropriate response  99% of integrated sensory information is subconsciously disregarded as unimportant/ Remaining sensory stimuli that CNS does respond to leads to motor response – Motor functions – actions performed in response to integration by motor (efferent) division of PNS; subdivided into somatic and autonomic divisions, by organs that neurons contact  Motor/efferent division – – Motor neurons carry out motor functions; travel from brain and spinal cord via cranial and spinal nerves – Effectors – organs that carry out effects of nervous system (subdivisions on next slide…) – Somatic motor division – neurons transmit signals to skeletal muscle; voluntary control (aka voluntary motor division) – Autonomic nervous system (ANS) or visceral motor division/ Neurons carry signals to thoracic and abdominal viscera; critical for maintaining homeostasis/ Regulates secretion of certain glands, contraction of smooth muscle, and contraction of cardiac muscle; involuntary (aka involuntary motor division) Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Functional Divisions of the Nervous System Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Functional Divisions of the Nervous System Figure 11.3 Summary of the structural and functional divisions of the nervous system. Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved MODULE 11.2 NERVOUS TISSUE Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Neurons Neurons – excitable cells responsible for sending and receiving signals as action potentials; most consist of three parts Cell body (soma) – most metabolically active region; manufactures all proteins needed for whole neuron; organelles support high level of biosynthetic activity: Both free ribosomes and rough endoplasmic reticulum (protein synthesis); RER visible with microscope (Nissl bodies)/ Golgi apparatus (vesicular transport) / Large or multiple nucleoli (ribosomal RNA)/ Mitochondria supply energy required/ Cytoskeleton – microtubules; structural support and chemical transportation between cell body and axon/ Neurofibrils – intermediate filaments of cytoskeleton; structural support extending into neuron processes Dendrites – short, branched processes; receive input from other neurons, which they transmit toward cell body as electrical impulses; each neuron may have multiple dendrites Each neuron has only one axon (nerve fiber); can generate and conduct action potentials; distinct regions of axon: Axon hillock – where axon originates from cell body/ Axon collaterals – branches extending from main axon Telodendria – small branches arising from axon and axon collaterals near where extensions end/ Axon terminals or synaptic bulbs – arise from telodendria; components that communicate with target cell/ Axolemma – plasma membrane surrounding axon and its cytoplasm (axoplasm) Substances travel through axoplasm by two types of axonal transport (flow): Slow axonal transport – transports substances (cytoskeleton proteins) from cell body through axon; rate of 1–3 mm/day/ Fast axonal transport – requires motor proteins and consumes ATP; vesicles and membrane-bound organelles travel back toward (retrograde) or away from (anterograde) cell body; maximum rate of 200 mm/day and 400 mm/day respectively Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Neurons Figure 11.4 Nervous tissue. Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Figure 11.5 Neuron structure. Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Poliovirus and Retrograde Axonal Transport Poliomyelitis – caused by poliovirus; infection impacts CNS and especially spinal cord; can result in deformity and paralysis No cure exists, but polio can be easily prevented by vaccination Virus accesses CNS by first entering muscle cells; passes into motor neurons at neuromuscular junction; travels length of axon by retrograde axonal transport until reaching spinal cord Other viruses (herpes simplex, rabies) and toxins (tetanus) also have ability to invade via this method Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Neurons Regions Neurons have three main functional regions: Receptive region – dendrites and cell body/ Conducting region – axon/ Secretory region – axon terminal Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Neurons classified by structural features Neurons can be classified according to structural features (Table 11.1): – Multipolar – single axon and multiple dendrites; over 99% of all neurons – Bipolar – one axon and one dendrite and cell body between them; eye and olfactory epithelium (nasal cavity) – Pseudounipolar – only one fused axon; extends from cell body; divides into two processes: one carries sensory information from sensory receptors to cell body; other carries sensory information (pain, touch, and pressure) from cell body to spinal cord; Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Table 11.1 Neuron Classification by structural features Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Neurons Classification by Function Neurons can also be classified into three functional groups. – Sensory (afferent) neurons – carry information toward CNS; neuron cell bodies in PNS receive information from sensory receptors and relay information via axons to brain or spinal cord; usually pseudounipolar or bipolar – Interneurons (association) neurons – relay information within CNS between sensory and motor neurons; most neurons in body; multipolar; communicate with many other neurons – Motor (efferent) neurons – carry information away from cell body in CNS to muscles and glands; mostly multipolar Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Specific Neuron components group together: Specific neuron components group together: – CNS:  Nuclei – clusters of neuron cell bodies  Tracts – bundles of axons – PNS:  Ganglia – clusters of neuron cell bodies  Nerves – bundles of axons Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Neuroglia Neuroglia (neuroglial) cells – provide structural support and protection for neurons; also maintain their environment (Figures 11.6, 11.7)/ Able to divide and fill in space left behind when neuron dies. – 4 types reside in CNS: Astrocytes. Oligodendrocytes. Microglia, and Ependymal cells Astrocytes – large star-shaped cells; many processes terminating in end-feet; function to:Anchor neurons and blood vessels in place; help define and maintain three-dimensional structure of brain/ Transport of nutrients and gases between blood vessels and neurons; regulate extracellular environment of brain/ Formation of blood-brain barrier; protective structure; surrounds capillary endothelial cells; makes them impenetrable to most polar compounds and proteins/ Repair damaged brain tissue by rapid cell division Oligodendrocytes – also in CNS; radiating processes with flattened sacs; wrap around axons of nearby neurons to form myelin Microglia – small, scarce cells; activated by injury into wandering phagocytic cells within CNS; ingest disease- causing microorganisms, dead neurons, and cellular debris Ependymal cells – ciliated cells; line hollow spaces within CNS (brain and spinal cord); manufacture and circulate cerebrospinal fluid (CSF) – 2 types reside in PNS:  Schwann cells (Neurolemocyte) - encircle axons in PNS to provide them with myelination.  Satellite cells – surround cell bodies of neurons in PNS; provide supportive functions (still not well defined) Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Figure 11.6 Neuroglial cells of the CNS. Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Figure 11.7 Neuroglial cells of the PNS. Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved The Myelin Sheath Myelin Sheath – layers of plasma membrane of Schwann cell or oligodendrocyte in PNS and CNS respectively Myelination – neuroglial cells wrap multiple layers of membrane (myelin) around axon – Lipid content of myelin sheath insulates axon (prevents ion movements) like rubber around copper wire; increases speed of action potential conduction/ Myelinated axons conduct action potentials about 15–20 times faster than unmyelinated axons – Neurolemma – on outer surface of myelinated axons in PNS; Schwann cell nucleus, organelles, and cytoplasm; not present in CNS (Figure 11.8a, b) – Number of axons myelinated – oligodendrocytes have multiple processes that myelinate multiple axons in CNS; Schwann cell only myelinates one axon in PNS – Timing of myelination – myelination begins early in fetal development in PNS and much later in CNS; very little myelin in brain of newborn Axons in both CNS and PNS are generally longer than neuroglial cells so multiple cells must provide complete myelin sheath – Internodes – segments of axon covered by neuroglia – Node of Ranvier – gap between adjacent neuroglia; where myelin sheath is absent Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Figure 11.8a The myelin sheath in the PNS and CNS. Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Figure 11.8b The myelin sheath in the PNS and CNS. Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved The Myelin Sheath Small axons in CNS and PNS are usually unmyelinated White matter – composed of myelinated axons; appear white Gray matter – composed of neuron cell bodies, unmyelinated dendrites and axons; appear gray Figure 11.9 Unmyelinated peripheral axons and Schwann cells. Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Figure 11.10 Repair of axon damage in the PNS. Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Regeneration of Nervous Tissue Regeneration or replacement of damaged tissue is nearly nonexistent in CNS; limited in PNS; neural tissue can regenerate only if cell body remains intact Regeneration steps (Figure 11.10): – Axon and myelin sheath degenerate distal to injury (Wallerian degeneration); facilitated by phagocytes – Growth processes form from proximal end of axon – Schwann cells and basal lamina form regeneration tube – Single growth process grows into regeneration tube; directs new axon toward its target cell – New axon reconnects to its target cell Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Figure 11.10 Repair of axon damage in the PNS. Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Gliomas and Astrocytomas Primary brain tumors – originate in brain; most are gliomas (caused by abnormally high rate of division of glial cells) Astrocyte – most commonly affected cell; tumor is astrocytoma Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved  MODULE 11.3 ELECTROPHYSIOLOGY OF NEURONS Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Introduction to Electrophysiology of Neurons All neurons are excitable (responsive) in presence of various stimuli: chemical signals, local electrical signals, and mechanical deformation Stimuli generate electrical changes across neuron plasma membrane; rapidly conducted (conductivity) along entire length of membrane Two forms of electrical changes occur in neurons: – Local potentials – travel short distances – Action potentials – travel entire length of axon Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved The Resting Membrane Potential Thin layer of negatively charged ions exists in cytosol on inside of cell; thin layer of positively charged ions exists on outside of cell Voltage – electrical gradient established by separation of charges between two locations (across plasma membrane) Membrane potential – electrical potential across cell membrane; source of potential energy for cell Typical neuron has resting membrane potential (RMP) of 70 mV (Figure 11.11a) – RMP is slightly negative because leakage channels favor gradient where more K+leaks out, than Na+leaks in (there are more K+channels than Na+ channels) – RMP of neuron is less negative at –70 mV than that of skeletal muscle fiber at –90 mV; largely due to number of potassium ion leak channels in skeletal muscle fiber – Cell is polarized when voltage difference across plasma membrane does not equal 0 mV Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved The Resting Membrane Potential (RMP) Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Principles of Electrophysiology Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Ion Channels and Gradients Electrical changes across neuron plasma membranes rely on ion channels and resting membrane potential: Ion channels – ions cannot diffuse through lipid component of plasma membrane; must rely on specific protein channels: – Leak channels – always open; continuously allow ions to flow down concentration gradients between cytosol and ECF – Gated channels – closed at rest; open in response to specific stimulus Gated channel types: – Ligand-gated channels – open in response to binding of specific chemical (ligand) to specific receptor – Voltage-gated channels – open in response to changes in voltage across membrane – Mechanically-gated channels – open or close in response to mechanical stimulation (pressure, stretch, or vibration) Ions moving against electrochemical gradients move via ATP-consuming pumps; one of most important is sodium- potassium ion pump (Na+/K+ ATPase) – Moves three Na+ ions out and two K+ions into cell, per ATP hydrolyzed/ Maintains (and to some extent creates) high concentration of Na+ in extracellular fluid and lower concentration in cytosol; opposite true for K+ Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Changes in Membrane Potential: Ion Movements Cell starts with negative resting membrane potential, (negative with respect to extracellular fluid) Unequal distribution of ions across plasma membrane exists; gradients are maintained by gated channels and pumps (Na+/K+ pump) When gated channels for specific ion open, ions will follow electrochemical gradient into or out of cell Can alter cell’s membrane potential by opening gated channels and causing ions to flow into or out of cell – Figure 11.11a shows membrane at rest (not being stimulated); gated ion channel is closed – In Figure 11.11b ligand binds ligand-gated cation channel, and cations (such as sodium ions) follow electrochemical gradient into cell; influx of positive charges makes membrane potential less negative (depolarization); cell becomes less polarized as membrane potential approaches 0 mV – When cell returns to resting membrane potential, repolarization has occurred – In Figure 11.11c, ligand binds to cation channel (such as a K+ channel) for which electrochemical gradient is reversed; cations flow out of cell into extracellular fluid  As cell loses positive charges, membrane potential becomes more negative than at rest (hyperpolarization)  Hyperpolarization may also result from opening of channels for anions (chloride ions); would allow negatively charged ions to flow into cell Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved  Figure 11.11 Ion movements leading to changes in the membrane potential. Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Local Anesthetic Drugs Local anesthetics – (lidocaine) commonly administered agents for surgical or dental procedures; produce temporary numbness in specific area Block voltage-gated sodium channels of neurons in treated area; prohibits depolarization; action potentials relaying pain are not transmitted to CNS Nonselective; also affect sodium channels in muscles of area; causes temporary paralysis; reason for crooked smiles and drooling following dental work Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Local Potentials & graded potentials Local potentials – small local changes in potential of neuron’s plasma membrane; triggers for long-distance action potentials May cause one of two effects (Figure 11.11): – Depolarization – positive charges enter cytosol; make membrane potential less negative (change from 70 to 60 mV) – Hyperpolarization – either positive charges exit or negative charges enter cytosol; makes membrane potential more negative (change from 70 to 80 mV) Sometimes called graded potentials; vary greatly in size; degree of change in membrane potential depends on length of stimulation, number of ion channels open, and type(s) of ion channels open. Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Voltage-gated potassium channels have two possible states: resting (closed) and activated (open) (Figure 11.12a)  Resting state – channels are closed; no potassium ions are able to cross plasma membrane  Activated state – channels are open; potassium ions are able to flow down concentration gradients Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Voltage-gated sodium channels Voltage-gated sodium channels have two gates (activation and inactivation gates) with three states (Figure 15.12b): – Resting state – inactivation gate is open and activation is closed; no sodium ions are able to move – Activated state – voltage change opens activation gate; both activation and inactivation gates are open when an action potential is initiated – Inactivated state – inactivation gate is closed and activation gate is open; channel no longer allows sodium ions to move through; once action potential is over, channel returns to resting state Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Figure 11.12b States of Na cation voltage-gated channels. Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Action Potentials Action potential – uniform, rapid depolarization and repolarization of membrane potential; only generated in trigger zones (axolemma, axon hillock, and initial segment of axon) States of voltage–gated channels – two types of voltage-gated channels involved in action potentials — one for sodium ions and one for potassium ions; most abundant in axolemma of neuron; why only axons have action potentials (Figure 11.12) Neuronal action potential has three general phases; lasts only few milliseconds: – Depolarization phase – membrane potential rises toward zero; then becomes positive briefly – Repolarization phase – membrane potential returns to negative value – Hyperpolarization phase – membrane potential temporarily becomes more negative than resting membrane potential Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Action Potentials Events Action potential proceeds through following steps (Figure 11.13): 1. Local potential must be able to depolarize axon strongly enough to reach level called threshold (usually 55 mV). 2. Once threshold reached, voltage-gated sodium channels activate and sodium ions flow into axon causing depolarization/ Positive Feedback loop – initial input (activation of sodium ion channels and depolarization) amplifies output (more sodium ion channels are activated and axolemma depolarizes further). 3. Sodium ion channels inactivate, and voltage-gated potassium ion channels activate; sodium ions stop flowing into axon; potassium begins exiting axon as repolarization begins. 4. Sodium ion channels return to resting state and repolarization continues. 5. Axolemma may hyperpolarize before potassium ion channels return to resting state; then axolemma returns to resting membrane potential. Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Figure 11.13 Events of an action potential. Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Figure 11.13 Events of an action potential. Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Refractory Period Refractory period – period after neuron has generated action potential; cannot be stimulated to generate another action potential; divided into two phases(Figure 11.14): Absolute refractory period – when no additional stimulus (no matter how strong) is able to produce additional action potential – Coincides with voltage-gated sodium channels being activated and inactivated – Sodium channels may not be activated until they return to resting states (activation gates closed and inactivation gates open) Relative refractory period – follows immediately after absolute refractory period; only strong stimulus can produce action potential – Voltage-gated sodium channels returned to resting state; able to open again – Potassium channels are activated, and membrane is repolarizing or hyperpolarizing; takes much larger stimulus to trigger action potential Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Figure 11.14 Refractory periods of an action potential. Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Local and Action Potentials Compared Graded local potentials produce variable changes in membrane potentials while actions potentials cause maximum depolarization to +30 mV All-or-none principle refers to event (action potential) that either happens completely or does not occur at all – If neuron does not depolarize to threshold, then no action potential will occur – Action potentials are not dependent on strength, frequency, or length of stimulus like local potentials Local potentials are reversible; when stimulus ends neuron returns to resting membrane potential; action potentials are irreversible; once threshold is reached it cannot be stopped; will proceed to completion (all-or-none) Signal distance is greater for action potentials versus “local” potentials: Local potentials are decremental; decrease in strength over short distance/ Action potentials are nondecremental; signal strength does not decrease despite traveling long distances Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Propagation of Action Potentials Action potentials must be conducted (propagated) along entire length of axon to serve as long-distance signaling service (Figures 11.15, 11.16): Action potentials – self-propagating; travel in only one direction: – Each action potential triggers another in next section of axon, usually starting at trigger zone and ending at axon terminals (like dominoes) – Action potentials travel in one direction as sodium ion channels of each successive section of axon go into refractory period as next section depolarizes – Action potential propagation down axon is nerve impulse Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Figure 11.15 Propagation of an action potential. Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Figure 11.15 Propagation of an action potential. Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Propagation of AP/ Conduction speed Conduction speed – rate of propagation; influenced by both axon diameter and myelination; determines how rapidly signaling can occur within nervous system – Axons with larger diameter have faster conduction speeds because larger axons have lower resistance to conduction (current flows through them more easily) – Presence of absence of myelination gives rise to two types of conduction: saltatory and continuous conduction (next) Continuous conduction – in unmyelinated axons; every section of axolemma from trigger zone to axon terminal must propagate action potential; slows conduction speed as each successive section of axon must depolarize Saltatory conduction – in myelinated axons where insulating properties of myelin sheath increase efficiency and speed of signal conduction; action potentials only depolarize nodes of Ranvier; “jumps” from node to node Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Propagation of Action Potentials Figure 11.16 Comparison of saltatory and continuous conduction. Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Propagation of Action Potentials Classification of Axons by Conduction Speed: – Type A fibers – fastest conduction speeds (120 m/sec or 250 mi/h); largest diameter (5–20 m) and myelinated; sensory and motor axons associated with skeletal muscle and joints – Type B fibers – slower conduction speeds (15 m/sec or 32 mi/hr); mostly myelinated with intermediate diameter axons (2–3 m); efferent fibers of autonomic nervous system (ANS) and some sensory axons – Type C fibers – slowest conduction speeds (0.5–2 m/sec or 1–5 mi/hr); smallest diameter fibers (0.5–1.5 m); unmyelinated axons include efferent fibers of ANS and sensory axons; transmit pain, temperature, and certain pressure sensations Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Multiple Sclerosis Multiple sclerosis (MS) – certain cells of immune system attack myelin sheaths within CNS; type of autoimmune disorder (patient’s own immune system attacks part of body) Causes progressive loss of myelin sheath; in turn causes loss of current from neurons Symptoms – result from progressive slowing of action potential propagation; depend on region of CNS affected; most exhibit changes in sensation (e.g., numbness), alterations in behavior and cognitive abilities, and motor dysfunction, including paralysis Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Putting It All Together: The Big Picture of Action Potentials Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved MODULE 11.4 NEURONAL SYNAPSES Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved  Overview of Neuronal Synapses Neurons must communicate with other cells, including other neurons, in order to carry out their functions – Cell–Cell Communication Core Principle Synapse – where neuron meets target cell (neuronal synapse if another neuron); can be electrical or chemical (Figure 11.21): Neuronal synapses can occur between axon of one neuron and another part of another neuron (next slide) – Axodendritic synapse – between axon of one neuron and dendrite of another – Axosomatic synapse – between axon of one neuron and cell body of another – Axoaxonic synapse – between axon of one neuron and axon of another Terms used to describe which neuron is sending and which is receiving message, regardless of type of synapse: – Presynaptic neuron – neuron sending message from its axon terminals – Postsynaptic neuron – neuron receiving message from presynaptic neuron at its cell body, axon, or dendrites Synaptic transmission – transfer of chemical or electrical signals between neurons at synapse; fundamental process for most functions of nervous system – Allows for voluntary movement, cognition, sensation, and emotions – Average presynaptic neuron forms synapses with about 1000 postsynaptic neurons – Postsynaptic neuron can have as many as 10,000 synaptic connections with different presynaptic neurons Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Figure 11.18 Structural types of synapses. Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Electrical Synapses Electrical synapse – occurs between cells electrically coupled via gap junctions (Figure 11.19a): – Axolemmas of each cell in synapse are nearly touching; gap junctions align channels forming pores that ions or other small substances can flow through – In areas of brain responsible for programmed, automatic behaviors (breathing) – In cardiac and visceral smooth muscle to allow for coordinated muscle activity – Electrical current can flow directly from axoplasm of one neuron to next; creates two unique features of electrical synapses:  Transmission is bidirectional – either neuron can be pre or postsynaptic; depends on direction current flows between them  Transmission is nearly instantaneous – only delay is time for presynaptic neuron to depolarize (less than 0.1 milliseconds); much faster than chemical synapses (1 or more milliseconds) Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Figure 11.19a The structures of electrical synapse Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Chemical Synapses Chemical Synapses (Figures 11.19, 11.20): – Make up majority of synapses in nervous system/ More efficient than electrical synapses; convert electrical signals into chemical signals; no signal strength is lost (as at electrical synapses) Events at Chemical Synapse – more complicated than neuromuscular junctions; multiple neurons secreting many different types of excitatory or inhibitory neurotransmitters (Figure 11.20): 1. Action potential in presynaptic neuron triggers opening of voltage-gated calcium ion channels in axon terminal 2. Influx of calcium ions causes synaptic vesicles to release neurotransmitter into synaptic cleft 3. Neurotransmitters bind to receptors on postsynaptic neuron 4. Ion channels open, leading to local potential and possibly action potential if threshold reached Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Electrical and Chemical Synapses Comparison Electrical and Chemical Synapses Compared –structural differences between chemical and electrical synapses (Figure 11.19b): – Synaptic vesicles – filled with chemical messengers (neurotransmitters); transmit signals from presynaptic to postsynaptic neurons at chemical synapses – Synaptic cleft – small ECF-filled space; separates presynaptic and postsynaptic neurons in chemical synapses (gap junctions connect neurons in electrical synapses) – Postsynaptic neuron has neurotransmitter receptors; bind neurotransmitter secreted from presynaptic neuron – Synaptic delay – time gap between arrival of action potential at axon terminal and effect on postsynaptic membrane – Chemical synapses are unidirectional (unlike electrical); allow for variable signal intensities; more neurotransmitter released from presynaptic neuron leads to stronger response at postsynaptic neuron Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved  Figure 11.19b The structures of chemical synapse. Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Figure 11.20 Events at a chemical synapse: synaptic transmission. Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Chemical Synapses/ Postsynaptic potentials Postsynaptic potentials – local potentials in membranes of postsynaptic neuron (Figure 11.21): – Membrane potential of postsynaptic neuron moves closer to threshold; caused by small local depolarization (sodium or calcium channels open) called excitatory postsynaptic potential (EPSP) – Membrane potential of postsynaptic neuron moves farther away from threshold; caused by small local hyperpolarization (potassium or chloride ion channels open) called inhibitory postsynaptic potential (IPSP) Neurons receive input, both inhibitory and excitatory, from multiple neurons, each of which influences whether action potential is generated/ Neural integration – process in which postsynaptic neuron integrates all incoming information into single effect Summation – all input from several postsynaptic potentials are added together (EPSPs + IPSPs) to affect membrane potential at trigger zone/ Action potential will only be generated if threshold is reached; sum of EPSPs must be enough to overcome sum of IPSPs/ If sum of IPSPs is greater than EPSPs, membrane will hyperpolarize; threshold will not be reached and action potential will not be generated Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Chemical Synapses/ Postsynaptic potentials Figure 11.21 Postsynaptic potentials. Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Neural Integration/ Types of summation Types of summation: – Temporal summation – neurotransmitter released repeatedly from axon terminal of single presynaptic neuron; each local potential (EPSP) is short-lived; must be generated quickly to reach threshold and create action potential (Figure 11.22a) – Spatial summation – simultaneous release of neurotransmitters from axon terminals of many presynaptic neurons (Figure 11.22b) IPSPs are also subject to both temporal and spatial summation but have inhibitory effects; make it less likely to reach threshold with subsequent action potential generation Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved  Neural Integration/ Temporal and spatial summation Figure 11.22 Temporal and spatial summation of excitatory postsynaptic potentials (EPSPs). Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Chemical Synapses/ Synaptic transmission Synaptic transmission may be terminated by ending effects of neurotransmitter (Figure 11.23): – Neurotransmitters diffuse away from synaptic cleft in ECF; can be reabsorbed into neuron or astrocyte – Neurotransmitter broken down in synaptic cleft by enzymes; by-products of reaction reabsorbed by presynaptic membrane for reassembly – Some neurotransmitters are reabsorbed into presynaptic neuron (reuptake) Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Figure 11.23 Methods of termination of synaptic transmission. Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Sorting out Different Types of Channels and Pumps in Membrane of a Neuron Distribution of protein channels and pumps is predictable if functions are considered: Ligand-gated ion channels bind neurotransmitters from another neuron (to receive signals); so ligand-gated ion channels will be located on receptive regions of neuron (dendrites and cell body) Voltage-gated sodium and potassium ion channels open or close during action potential to send signal to another cell; located on part of neuron that sends signals to other cells via action potentials (axon) Voltage-gated calcium ion channels trigger exocytosis of synaptic vesicles; only one place in neuron where synaptic vesicles are located (axon terminal) Leak channels and Na+/K+ pump generate and maintain resting membrane potential; RMP applies to entire neuron, so leak channels and Na+/K+ pumps are located throughout every part of neuron’s membrane Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Figure 11.24 Types of channels and pumps in different parts of the neuron membrane. Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Arthropod Venom Venomous arthropods (in US) include spiders and scorpions; many venoms affect neuronal synapses; termed neurotoxins – Female black widow (Latrodectus mactans) – toxin causes massive release of neurotransmitter; causes repetitive stimulation of postsynaptic neuron – Bark scorpion – most lethal of 40 species in US; venom prevents postsynaptic sodium channels from closing; membrane remains polarized; continues to fire action potentials Common symptoms – muscle hyperexcitability, sweating, nausea and vomiting, and difficulty breathing Treatment and prognosis – depends on amount of venom received and availability of medical care; severe cases usually require antivenin to block effects of toxin Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Putting It All Together: The Big Picture of Chemical Synaptic Transmission Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved  MODULE 11.5 NEUROTRANSMITTERS Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Neurotransmitters Nearly all neurotransmitters undergo similar pattern of use despite that there are over 100 known; share similar features: – Made in cell body or axon terminal and packaged into synaptic vesicles – Released from axon terminals of presynaptic neurons; cross synaptic cleft; bind to specific receptors on postsynaptic membrane – Effects are often rapidly terminated through removal and/or degradation Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Neurotransmitter Receptor Type of neurotransmitter receptor on postsynaptic membrane determines response: – Ionotropic receptors – components of ligand-gated ion channels; directly control movement of ions into or out of neuron when bind to neurotransmitter (Figure 11.26a) – Metabotropic receptors – within plasma membrane; associated with separate ion channel; connected to metabolic processes initiated when neurotransmitter binds (Figure 11.26b)  G-proteins – group of intracellular enzymes associated with many metabotropic receptors; activate cascade of enzyme-catalyzed reactions; form intracellular chemical messenger molecules called second messengers (neurotransmitter is “first messenger”)  Second messengers – open or close ion channels in postsynaptic membrane – Cyclic adenosine monophosphate (cAMP) – common second messenger derived from ATP; multiple functions in neurons – cAMP binds to group of enzymes; add phosphate groups to ion channels; triggers channel to open or close Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved  Neurotransmitter Receptor Figure 11.26 Types of neurotransmitter receptors (Ionotropic and Metabotropic receptors) Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Major Neurotransmitters Binding of neurotransmitter to receptor leads to an EPSP (excitatory effects) or an IPSP (inhibitory effects) Most neurotransmitters can have both effects; depends on which postsynaptic neuron receptors they bind; single neurotransmitter may have several receptor types Major neurotransmitters are classified into four groups based on chemical structure Acetylcholine (ACh) Biogenic amines amino acid neurotransmitters Neuropeptides Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Table 11.3 4 Major Neurotransmitters Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Major Neurotransmitters/ ACh Acetylcholine (ACh) – small molecule neurotransmitter widely used by nervous system – Cholinergic synapses bind ACh; in neuromuscular junction, within brain and spinal cord and within autonomic nervous system – Largely excitatory; does exhibit some inhibitory effects in PNS – Synthesized from choline and acetyl-CoA; packed into synaptic vesicles – Quickly degraded by acetylcholinesterase (AChE); enzyme in synaptic cleft; by-products taken back into presynaptic neuron for recycling and reuse Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Major Neurotransmitters/ Biogenic amines Biogenic amines (monoamines); five neurotransmitters synthesized from amino acids; used throughout CNS and PNS for regulation of homeostasis and cognition; first three form catecholamine subgroup (made from amino acid tyrosine); mostly excitatory: – Norepinephrine (catecholamine; noradrenalin) – mainly in ANS; influences heart rate, blood pressure, and digestion; in CNS regulates sleep/wake cycle, attention, and feeding behaviors – Epinephrine (catecholamine; adrenalin) – also in ANS; similar functions as norepinephrine; more widely used as hormone by endocrine system. – Dopamine (catecholamine) – used extensively by CNS; movement coordination, emotion and motivation – Serotonin – synthesized from amino acid tryptophan; most serotonin-secreting neurons are in brainstem; axons project into multiple areas of brain; functions include mood regulation, emotions, attention, feeding behaviors, and daily rhythms – Histamine – synthesized from amino acid histidine; regulation of arousal and attention Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Major Neurotransmitters/ Monoamines Three main Aminoacid neurotransmitters (Monoamines): – Glutamate – most important excitatory neurotransmitter in CNS; binds to ionotropic postsynaptic receptors; opens channels that allow flow of both sodium and calcium ions; generate EPSPs in postsynaptic neuron – Glycine and GABA – both major inhibitory neurotransmitters; induce IPSPs on postsynaptic neurons by opening chloride ion channels; hyperpolarize axolemma Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Major Neurotransmitters/ Neuropeptide Neuropeptides – group of neurotransmitters with wide variety of functions; must be synthesized in cell body and transported to axon – Substance P – released from type C sensory afferents that carry information about pain and temperature; also released by other neurons in brain, spinal cord, and gut – Opioids – group of more than 20 neuropeptides; include endorphins, enkephalins, and dynorphins; all elicit pain relief; nervous system depressants – Neuropeptide Y – feeding behaviors; may mediate hunger or feeling full Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Psychiatric Disorders and Treatments Psychopharmacology (study of drugs that affect higher brain functions) targets either action potential generation or some aspect of neurotransmitter physiology Psychiatric disorders affect thought processes; generally treated by modifying synaptic transmission to change how neurons communicate – Schizophrenia – repetitive psychotic episodes (periods during which patient is unable to appropriately test beliefs and perceptions against reality); thought to result from excessive release of dopamine; management involves blocking postsynaptic dopamine receptors – Depressive disorders – disturbances in mood; thought to result from deficiency in synaptic transmission of serotonin, norepinephrine, and/or dopamine; most widely used antidepressants are selective serotonin reuptake inhibitors (SSRIs); block serotonin transporter (only), preventing reuptake by presynaptic neuron – Anxiety disorders – exaggerated and inappropriate fear responses; believed to stem from abnormalities in norepinephrine, serotonin, and GABA transmission; treated with antidepressants, GABA activity enhancers, and others that modulate norepinephrine transmission – Bipolar disorders – characterized by episodes of abnormal elevated mood (mania) followed by depression; treatments involve decreasing ease of action potential generation; generally block sodium channels in axolemma Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved MODULE 11.6 FUNCTIONAL GROUPS OF NEURONS Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Neuronal Pools Neuronal pools – groups of interneurons within CNS (Figure 11.27): Composed of neuroglial cells, dendrites, and axons in one location and cell bodies in another location/ Type of information processed by pool is defined by synaptic connections of pool/ Connections between pools allow for complex mental activity (planned movement, cognition, and personality)/ Input neurons initiate series of signals that starts activity of pool Neural circuits – patterns of synaptic connection between neural pools; two basic types of neural circuits (Figure 11.28): – Diverging circuits begin with single input neuron axon; branches out to make contact with multiple postsynaptic neurons that follow same pattern (Figure 11.28a)  Allow single neuron to communicate with multiple parts of brain and/or body/ Characteristic of those transmitting incoming sensory information sent from spinal cord to different neuronal pools in brain for processing – Converging circuits – opposite configuration of diverging circuits; axon terminals from multiple input neurons converge onto single postsynaptic neuron (Figure 11.28b)  Control of skeletal muscle movement/ Allow nervous system to respond to sensory information that it collects and processes CNS has two mechanisms that stabilize neural circuits; prevent electrical activity from becoming chaotic: – Inhibitory circuits provide negative feedback mechanism to control activity of other neural circuits – Synaptic fatigue – synaptic transmission becomes progressively weaker with prolonged and intense excitation Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Figure 11.27 A neuronal pool. Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Neuronal Converging circuits Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved Epileptic Seizures Epilepsy – recurrent episodes of abnormal, disorganized electrical activity in brain (seizures) Result from sudden bursts of excitatory electrical activity within neuronal pool; may be triggered by instability in membrane potential of single neuron Excess excitation overwhelms inhibitory circuits that normally prevent overexcitation Continuous wave of excitation spreads over part of brain (partial seizure) or entire brain (generalized seizure); no meaningful signals can be transmitted; ends due to synaptic fatigue Symptoms – mild sensory disturbances to loss of consciousness to characteristic jerking movements Therapy – medications aimed at preventing seizures and allowing inhibitory circuits to function properly Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved