Power Point Lecture Slides prepared by Barbara Heard

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Power. Point® Lecture Slides prepared by Barbara Heard, Atlantic Cape Community Ninth Edition College

Power. Point® Lecture Slides prepared by Barbara Heard, Atlantic Cape Community Ninth Edition College Human Anatomy & Physiology CHAPTER 11 Fundamentals of the Nervous System and Nervous Tissue: Part C © Annie Leibovitz/Contact Press Images © 2013 Pearson Education, Inc.

The Synapse • Nervous system works because information flows from neuron to neuron •

The Synapse • Nervous system works because information flows from neuron to neuron • Neurons functionally connected by synapses – Junctions that mediate information transfer • From one neuron to another neuron • Or from one neuron to an effector cell © 2013 Pearson Education, Inc.

Synapse Classification • Axodendritic—between axon terminals of one neuron and dendrites of others •

Synapse Classification • Axodendritic—between axon terminals of one neuron and dendrites of others • Axosomatic—between axon terminals of one neuron and soma of others • Less common types: – Axoaxonal (axon to axon) – Dendrodendritic (dendrite to dendrite) – Somatodendritic (dendrite to soma) © 2013 Pearson Education, Inc.

Important Terminology • Presynaptic neuron – Neuron conducting impulses toward synapse – Sends the

Important Terminology • Presynaptic neuron – Neuron conducting impulses toward synapse – Sends the information • Postsynaptic neuron (in Pns may be a neuron, muscle cell, or gland cell) – Neuron transmitting electrical signal away from synapse – Receives the information • Most function as both PLAY Animation: Synapses © 2013 Pearson Education, Inc.

Figure 11. 16 Synapses. Axodendritic synapses Dendrites Axosomatic synapses Cell body Axoaxonal synapses Axon

Figure 11. 16 Synapses. Axodendritic synapses Dendrites Axosomatic synapses Cell body Axoaxonal synapses Axon Axosomatic synapses Cell body (soma) of postsynaptic neuron © 2013 Pearson Education, Inc.

Varieties of Synapses: Electrical Synapses • Less common than chemical synapses – Neurons electrically

Varieties of Synapses: Electrical Synapses • Less common than chemical synapses – Neurons electrically coupled (joined by gap junctions that connect cytoplasm of adjacent neurons) • Communication very rapid • May be unidirectional or bidirectional • Synchronize activity – More abundant in: • Embryonic nervous tissue • Nerve impulse remains electrical © 2013 Pearson Education, Inc.

Varieties of Synapses: Chemical Synapses • Specialized for release and reception of chemical neurotransmitters

Varieties of Synapses: Chemical Synapses • Specialized for release and reception of chemical neurotransmitters • Typically composed of two parts – Axon terminal of presynaptic neuron • Contains synaptic vesicles filled with neurotransmitter – Neurotransmitter receptor region on postsynaptic neuron's membrane • Usually on dendrite or cell body • Two parts separated by synaptic cleft – Fluid-filled space • Electrical impulse changed to chemical across synapse, then back into electrical © 2013 Pearson Education, Inc.

Synaptic Cleft • 30 – 50 nm wide (~1/1, 000 th of an inch)

Synaptic Cleft • 30 – 50 nm wide (~1/1, 000 th of an inch) • Prevents nerve impulses from directly passing from one neuron to next © 2013 Pearson Education, Inc.

Synaptic Cleft • Transmission across synaptic cleft – Chemical event (as opposed to an

Synaptic Cleft • Transmission across synaptic cleft – Chemical event (as opposed to an electrical one) – Depends on release, diffusion, and receptor binding of neurotransmitters – Ensures unidirectional communication between neurons PLAY Animation: Neurotransmitters © 2013 Pearson Education, Inc.

Information Transfer Across Chemical Synapses • AP arrives at axon terminal of presynaptic neuron

Information Transfer Across Chemical Synapses • AP arrives at axon terminal of presynaptic neuron • Causes voltage-gated Ca 2+ channels to open – Ca 2+ floods into cell • Synaptotagmin protein binds Ca 2+ and promotes fusion of synaptic vesicles with axon membrane • Exocytosis of neurotransmitter into synaptic cleft occurs – Higher impulse frequency more released © 2013 Pearson Education, Inc.

Information Transfer Across Chemical Synapses • Neurotransmitter diffuses across synapse • Binds to receptors

Information Transfer Across Chemical Synapses • Neurotransmitter diffuses across synapse • Binds to receptors on postsynaptic neuron – Often chemically gated ion channels • Ion channels are opened • Causes an excitatory or inhibitory event (graded potential) • Neurotransmitter effects terminated © 2013 Pearson Education, Inc.

Termination of Neurotransmitter Effects • Within a few milliseconds neurotransmitter effect terminated in one

Termination of Neurotransmitter Effects • Within a few milliseconds neurotransmitter effect terminated in one of three ways – Reuptake • By astrocytes or axon terminal – Degradation • By enzymes – Diffusion • Away from synaptic cleft © 2013 Pearson Education, Inc.

Figure 11. 17 Chemical synapses transmit signals from one neuron to another using neurotransmitters.

Figure 11. 17 Chemical synapses transmit signals from one neuron to another using neurotransmitters. Presynaptic neuron Postsynaptic neuron 1 Action potential arrives at axon terminal. 2 Voltage-gated Ca 2+ channels open and Ca 2+ enters the axon terminal. 3 Ca 2+ entry causes synaptic vesicles to release neurotransmitter by exocytosis Axon terminal Mitochondrion Synaptic cleft Synaptic vesicles 4 Neurotransmitter diffuses across the synaptic cleft and binds to specific receptors on the postsynaptic membrane. Postsynaptic neuron Ion movement Graded potential Reuptake Enzymatic degradation Diffusion away from synapse 5 Binding of neurotransmitter opens ion channels, resulting in graded potentials. 6 Neurotransmitter effects are terminated by reuptake through transport proteins, enzymatic degradation, or diffusion away from the synapse. © 2013 Pearson Education, Inc.

Figure 11. 17 Chemical synapses transmit signals from one neuron to another using neurotransmitters.

Figure 11. 17 Chemical synapses transmit signals from one neuron to another using neurotransmitters. Presynaptic neuron Postsynaptic neuron 1 Action potential arrives at axon terminal. Mitochondrion Axon terminal Synaptic cleft Synaptic vesicles Postsynaptic neuron © 2013 Pearson Education, Inc.

Figure 11. 17 Chemical synapses transmit signals from one neuron to another using neurotransmitters.

Figure 11. 17 Chemical synapses transmit signals from one neuron to another using neurotransmitters. Presynaptic neuron Postsynaptic neuron 1 Action potential arrives at axon terminal. 2 Voltage-gated Ca 2+ channels open and Ca 2+ enters the axon terminal. Axon terminal Mitochondrion Synaptic cleft Synaptic vesicles Postsynaptic neuron © 2013 Pearson Education, Inc.

Figure 11. 17 Chemical synapses transmit signals from one neuron to another using neurotransmitters.

Figure 11. 17 Chemical synapses transmit signals from one neuron to another using neurotransmitters. Presynaptic neuron Postsynaptic neuron 1 Action potential arrives at axon terminal. 2 Voltage-gated Ca 2+ channels open and Ca 2+ enters the axon terminal. 3 Ca 2+ entry causes synaptic vesicles to release neurotransmitter by exocytosis Axon terminal Mitochondrion Synaptic cleft Synaptic vesicles Postsynaptic neuron © 2013 Pearson Education, Inc.

Figure 11. 17 Chemical synapses transmit signals from one neuron to another using neurotransmitters.

Figure 11. 17 Chemical synapses transmit signals from one neuron to another using neurotransmitters. Presynaptic neuron Postsynaptic neuron 1 Action potential arrives at axon terminal. 2 Voltage-gated Ca 2+ channels open and Ca 2+ enters the axon terminal. 3 Ca 2+ entry causes synaptic vesicles to release neurotransmitter by exocytosis 4 Neurotransmitter diffuses across the synaptic cleft and binds to specific receptors on the postsynaptic membrane. © 2013 Pearson Education, Inc. Axon terminal Mitochondrion Synaptic cleft Synaptic vesicles Postsynaptic neuron

Figure 11. 17 Chemical synapses transmit signals from one neuron to another using neurotransmitters.

Figure 11. 17 Chemical synapses transmit signals from one neuron to another using neurotransmitters. Ion movement Graded potential 5 Binding of neurotransmitter opens ion channels, resulting in graded potentials. © 2013 Pearson Education, Inc.

Figure 11. 17 Chemical synapses transmit signals from one neuron to another using neurotransmitters.

Figure 11. 17 Chemical synapses transmit signals from one neuron to another using neurotransmitters. Reuptake Enzymatic degradation Diffusion away from synapse 6 Neurotransmitter effects are terminated by reuptake through transport proteins, enzymatic degradation, or diffusion away from the synapse. © 2013 Pearson Education, Inc.

Figure 11. 17 Chemical synapses transmit signals from one neuron to another using neurotransmitters.

Figure 11. 17 Chemical synapses transmit signals from one neuron to another using neurotransmitters. Presynaptic neuron Postsynaptic neuron 1 Action potential arrives at axon terminal. 2 Voltage-gated Ca 2+ channels open and Ca 2+ enters the axon terminal. 3 Ca 2+ entry causes synaptic vesicles to release neurotransmitter by exocytosis Axon terminal Mitochondrion Synaptic cleft Synaptic vesicles 4 Neurotransmitter diffuses across the synaptic cleft and binds to specific receptors on the postsynaptic membrane. Postsynaptic neuron Ion movement Graded potential Reuptake Enzymatic degradation Diffusion away from synapse 5 Binding of neurotransmitter opens ion channels, resulting in graded potentials. 6 Neurotransmitter effects are terminated by reuptake through transport proteins, enzymatic degradation, or diffusion away from the synapse. © 2013 Pearson Education, Inc.

Synaptic Delay • Time needed for neurotransmitter to be released, diffuse across synapse, and

Synaptic Delay • Time needed for neurotransmitter to be released, diffuse across synapse, and bind to receptors – 0. 3– 5. 0 ms • Synaptic delay is rate-limiting step of neural transmission © 2013 Pearson Education, Inc.

Postsynaptic Potentials • Neurotransmitter receptors cause graded potentials that vary in strength with –

Postsynaptic Potentials • Neurotransmitter receptors cause graded potentials that vary in strength with – Amount of neurotransmitter released and – Time neurotransmitter stays in area © 2013 Pearson Education, Inc.

Table 11. 2 Comparison of Graded Potentials and Action Potentials (1 of 4) ©

Table 11. 2 Comparison of Graded Potentials and Action Potentials (1 of 4) © 2013 Pearson Education, Inc.

Table 11. 2 Comparison of Graded Potentials and Action Potentials (2 of 4) ©

Table 11. 2 Comparison of Graded Potentials and Action Potentials (2 of 4) © 2013 Pearson Education, Inc.

Table 11. 2 Comparison of Graded Potentials and Action Potentials (3 of 4) ©

Table 11. 2 Comparison of Graded Potentials and Action Potentials (3 of 4) © 2013 Pearson Education, Inc.

Table 11. 2 Comparison of Graded Potentials and Action Potentials (4 of 4) ©

Table 11. 2 Comparison of Graded Potentials and Action Potentials (4 of 4) © 2013 Pearson Education, Inc.

Postsynaptic Potentials • Types of postsynaptic potentials – EPSP—excitatory postsynaptic potentials – IPSP—inhibitory postsynaptic

Postsynaptic Potentials • Types of postsynaptic potentials – EPSP—excitatory postsynaptic potentials – IPSP—inhibitory postsynaptic potentials © 2013 Pearson Education, Inc.

Excitatory Synapses and EPSPs • Neurotransmitter binding opens chemically gated channels • Allows simultaneous

Excitatory Synapses and EPSPs • Neurotransmitter binding opens chemically gated channels • Allows simultaneous flow of Na+ and K+ in opposite directions • Na+ influx greater than K+ efflux net depolarization called EPSP (not AP) • EPSP help trigger AP if EPSP is of threshold strength – Can spread to axon hillock, trigger opening of voltage-gated channels, and cause AP to be generated © 2013 Pearson Education, Inc.

Membrane potential (m. V) Figure 11. 18 a Postsynaptic potentials can be excitatory or

Membrane potential (m. V) Figure 11. 18 a Postsynaptic potentials can be excitatory or inhibitory. +30 0 Threshold – 55 – 70 An EPSP is a local depolarization of the postsynaptic membrane that brings the neuron closer to AP threshold. Neurotransmitter binding opens chemically gated ion channels, allowing Na+ and K+ to pass through simultaneously. Stimulus 10 20 30 Time (ms) Excitatory postsynaptic potential (EPSP) © 2013 Pearson Education, Inc.

Inhibitory Synapses and IPSPs • Reduces postsynaptic neuron's ability to produce an action potential

Inhibitory Synapses and IPSPs • Reduces postsynaptic neuron's ability to produce an action potential – Makes membrane more permeable to K+ or Cl – • If K+ channels open, it moves out of cell • If Cl- channels open, it moves into cell – Therefore neurotransmitter hyperpolarizes cell • Inner surface of membrane becomes more negative • AP less likely to be generated © 2013 Pearson Education, Inc.

Membrane potential (m. V) Figure 11. 18 b Postsynaptic potentials can be excitatory or

Membrane potential (m. V) Figure 11. 18 b Postsynaptic potentials can be excitatory or inhibitory. +30 0 Threshold An IPSP is a local hyperpolarization of the postsynaptic membrane that drives the neuron away from AP threshold. Neurotransmitter binding opens K+ or Cl– channels. – 55 – 70 Stimulus 10 20 30 Time (ms) Inhibitory postsynaptic potential (IPSP) © 2013 Pearson Education, Inc.

Synaptic Integration: Summation • A single EPSP cannot induce an AP • EPSPs can

Synaptic Integration: Summation • A single EPSP cannot induce an AP • EPSPs can summate to influence postsynaptic neuron • IPSPs can also summate • Most neurons receive both excitatory and inhibitory inputs from thousands of other neurons – Only if EPSP's predominate and bring to threshold AP © 2013 Pearson Education, Inc.

Two Types of Summation • Temporal summation – One or more presynaptic neurons transmit

Two Types of Summation • Temporal summation – One or more presynaptic neurons transmit impulses in rapid-fire order • Spatial summation – Postsynaptic neuron stimulated simultaneously by large number of terminals at same time © 2013 Pearson Education, Inc.

Figure 11. 19 a Neural integration of EPSPs and IPSPs. Membrane potential (m. V)

Figure 11. 19 a Neural integration of EPSPs and IPSPs. Membrane potential (m. V) E 1 0 Threshold of axon of postsynaptic neuron Resting potential – 55 – 70 E 1 Time No summation: 2 stimuli separated in time cause EPSPs that do not add together. Excitatory synapse 1 (E 1) Excitatory synapse 2 (E 2) © 2013 Pearson Education, Inc. Inhibitory synapse (I 1)

Figure 11. 19 b Neural integration of EPSPs and IPSPs. Membrane potential (m. V)

Figure 11. 19 b Neural integration of EPSPs and IPSPs. Membrane potential (m. V) E 1 0 Resting potential Threshold of axon of postsynaptic neuron – 55 – 70 E 1 Time Temporal summation: 2 excitatory stimuli close in time cause EPSPs that add together. Excitatory synapse 1 (E 1) Excitatory synapse 2 (E 2) © 2013 Pearson Education, Inc. Inhibitory synapse (I 1)

Figure 11. 19 c Neural integration of EPSPs and IPSPs. E 1 Membrane potential

Figure 11. 19 c Neural integration of EPSPs and IPSPs. E 1 Membrane potential (m. V) E 2 0 Resting potential Threshold of axon of postsynaptic neuron – 55 – 70 E 1 + E 2 Time Spatial summation: 2 simultaneous stimuli at different locations cause EPSPs that add together. Excitatory synapse 1 (E 1) Excitatory synapse 2 (E 2) © 2013 Pearson Education, Inc. Inhibitory synapse (I 1)

Figure 11. 19 d Neural integration of EPSPs and IPSPs. E 1 Membrane potential

Figure 11. 19 d Neural integration of EPSPs and IPSPs. E 1 Membrane potential (m. V) l 1 0 – 55 – 70 l 1 E 1 + l 1 Time Spatial summation of EPSPs and IPSPs: Changes in membrane potential cancel each other out. Excitatory synapse 1 (E 1) Excitatory synapse 2 (E 2) © 2013 Pearson Education, Inc. Inhibitory synapse (I 1)

Integration: Synaptic Potentiation • Repeated use of synapse increases ability of presynaptic cell to

Integration: Synaptic Potentiation • Repeated use of synapse increases ability of presynaptic cell to excite postsynaptic neuron – Ca 2+ concentration increases in presynaptic terminal and postsynaptic neuron • Brief high-frequency stimulation partially depolarizes postsynaptic neuron – Chemically gated channels (NMDA receptors) allow Ca 2+ entry – Ca 2+ activates kinase enzymes that promote more effective responses to subsequent stimuli © 2013 Pearson Education, Inc.

Integration: Presynaptic Inhibition • Excitatory neurotransmitter release by one neuron inhibited by another neuron

Integration: Presynaptic Inhibition • Excitatory neurotransmitter release by one neuron inhibited by another neuron via an axoaxonal synapse • Less neurotransmitter released • Smaller EPSPs formed © 2013 Pearson Education, Inc.

Neurotransmitters • Language of nervous system • 50 or more neurotransmitters have been identified

Neurotransmitters • Language of nervous system • 50 or more neurotransmitters have been identified • Most neurons make two or more neurotransmitters – Neurons can exert several influences • Usually released at different stimulation frequencies • Classified by chemical structure and by function © 2013 Pearson Education, Inc.

Classification of Neurotransmitters: Chemical Structure • Acetylcholine (ACh) – First identified; best understood –

Classification of Neurotransmitters: Chemical Structure • Acetylcholine (ACh) – First identified; best understood – Released at neuromuscular junctions , by some ANS neurons, by some CNS neurons – Synthesized from acetic acid and choline by enzyme choline acetyltransferase – Degraded by enzyme acetylcholinesterase (ACh. E) © 2013 Pearson Education, Inc.

Classification of Neurotransmitters: Chemical Structure • Biogenic amines • Catecholamines – Dopamine, norepinephrine (NE),

Classification of Neurotransmitters: Chemical Structure • Biogenic amines • Catecholamines – Dopamine, norepinephrine (NE), and epinephrine – Synthesized from amino acid tyrosine • Indolamines – Serotonin and histamine – Serotonin synthesized from amino acid tryptophan; histamine synthesized from amino acid histidine • Broadly distributed in brain – Play roles in emotional behaviors and biological clock • Some ANS motor neurons (especially NE) • Imbalances associated with mental illness © 2013 Pearson Education, Inc.

Classification of Neurotransmitters: Chemical Structure • Amino acids • Glutamate • Aspartate • Glycine

Classification of Neurotransmitters: Chemical Structure • Amino acids • Glutamate • Aspartate • Glycine • GABA—gamma ( )-aminobutyric acid © 2013 Pearson Education, Inc.

Classification of Neurotransmitters: Chemical Structure • Peptides (neuropeptides) • Substance P – Mediator of

Classification of Neurotransmitters: Chemical Structure • Peptides (neuropeptides) • Substance P – Mediator of pain signals • Endorphins – Beta endorphin, dynorphin and enkephalins – Act as natural opiates; reduce pain perception • Gut-brain peptides – Somatostatin and cholecystokinin © 2013 Pearson Education, Inc.

Classification of Neurotransmitters: Chemical Structure • Purines – ATP! – Adenosine • Potent inhibitor

Classification of Neurotransmitters: Chemical Structure • Purines – ATP! – Adenosine • Potent inhibitor in brain • Caffeine blocks adenosine receptors – Act in both CNS and PNS – Produce fast or slow responses – Induce Ca 2+ influx in astrocytes © 2013 Pearson Education, Inc.

Classification of Neurotransmitters: Chemical Structure • Gases and lipids - gasotransmitters • Nitric oxide

Classification of Neurotransmitters: Chemical Structure • Gases and lipids - gasotransmitters • Nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide gases (H 2 S) • Bind with G protein–coupled receptors in the brain • Lipid soluble • Synthesized on demand • NO involved in learning and formation of new memories; brain damage in stroke patients, smooth muscle relaxation in intestine • H 2 S acts directly on ion channels to alter function © 2013 Pearson Education, Inc.

Classification of Neurotransmitters: Chemical Structure – Endocannabinoids • Act at same receptors as THC

Classification of Neurotransmitters: Chemical Structure – Endocannabinoids • Act at same receptors as THC (active ingredient in marijuana) – Most common G protein-linked receptors in brain • • Lipid soluble Synthesized on demand Believed involved in learning and memory May be involved in neuronal development, controlling appetite, and suppressing nausea © 2013 Pearson Education, Inc.

Classification of Neurotransmitters: Function • Great diversity of functions • Can classify by –

Classification of Neurotransmitters: Function • Great diversity of functions • Can classify by – Effects – excitatory versus inhibitory – Actions – direct versus indirect © 2013 Pearson Education, Inc.

Classification of Neurotransmitters: Function • Effects - excitatory versus inhibitory – Neurotransmitter effects can

Classification of Neurotransmitters: Function • Effects - excitatory versus inhibitory – Neurotransmitter effects can be excitatory (depolarizing) and/or inhibitory (hyperpolarizing) – Effect determined by receptor to which it binds • GABA and glycine usually inhibitory • Glutamate usually excitatory • Acetylcholine and NE bind to at least two receptor types with opposite effects – ACh excitatory at neuromuscular junctions in skeletal muscle – ACh inhibitory in cardiac muscle © 2013 Pearson Education, Inc.

Classification of Neurotransmitters: Direct versus Indirect Actions • Direct action – Neurotransmitter binds to

Classification of Neurotransmitters: Direct versus Indirect Actions • Direct action – Neurotransmitter binds to and opens ion channels – Promotes rapid responses by altering membrane potential – Examples: ACh and amino acids © 2013 Pearson Education, Inc.

Figure 11. 20 Direct neurotransmitter receptor mechanism: Channel-linked receptors. Ion flow blocked Ions flow

Figure 11. 20 Direct neurotransmitter receptor mechanism: Channel-linked receptors. Ion flow blocked Ions flow Ligand Closed ion channel © 2013 Pearson Education, Inc. Open ion channel

Classification of Neurotransmitters: Direct versus Indirect Actions • Indirect action – Neurotransmitter acts through

Classification of Neurotransmitters: Direct versus Indirect Actions • Indirect action – Neurotransmitter acts through intracellular second messengers, usually G protein pathways – Broader, longer-lasting effects similar to hormones – Biogenic amines, neuropeptides, and dissolved gases © 2013 Pearson Education, Inc.

Figure 11. 21 Indirect neurotransmitter receptor mechanism: G protein-inked receptors. Recall from Chapter 3

Figure 11. 21 Indirect neurotransmitter receptor mechanism: G protein-inked receptors. Recall from Chapter 3 that G protein signaling mechanisms are like a molecular relay race. Ligand (1 st Receptor messenger) G protein Enzyme 1 Neurotransmitter (1 st messenger) binds and activates receptor. 2 nd messenger Adenylate cyclase Closed ion channel Open ion channel Receptor G protein 5 a c. AMP changes membrane permeability by opening or closing ion channels. GDP 2 Receptor activates G protein. © 2013 Pearson Education, Inc. 3 G protein activates adenylate cyclase. 4 Adenylate cyclase converts ATP to c. AMP (2 nd messenger). 5 c c. AMP activates specific genes. 5 b c. AMP activates enzymes. Active enzyme Nucleus

Neurotransmitter Receptors • Types – Channel-linked receptors • Mediate fast synaptic transmission – G

Neurotransmitter Receptors • Types – Channel-linked receptors • Mediate fast synaptic transmission – G protein-linked receptor • Oversee slow synaptic responses © 2013 Pearson Education, Inc.

Channel-Linked (Ionotropic) Receptors: Mechanism of Action • Ligand-gated ion channels • Action is immediate

Channel-Linked (Ionotropic) Receptors: Mechanism of Action • Ligand-gated ion channels • Action is immediate and brief • Excitatory receptors are channels for small cations – Na+ influx contributes most to depolarization • Inhibitory receptors allow Cl– influx that causes hyperpolarization © 2013 Pearson Education, Inc.

Figure 11. 20 Direct neurotransmitter receptor mechanism: Channel-linked receptors. Ion flow blocked Ions flow

Figure 11. 20 Direct neurotransmitter receptor mechanism: Channel-linked receptors. Ion flow blocked Ions flow Ligand Closed ion channel © 2013 Pearson Education, Inc. Open ion channel

G Protein-Linked (Metabotropic) Receptors: Mechanism of Action • Responses are indirect, complex, slow, and

G Protein-Linked (Metabotropic) Receptors: Mechanism of Action • Responses are indirect, complex, slow, and often prolonged • Transmembrane protein complexes • Cause widespread metabolic changes • Examples: muscarinic ACh receptors, receptors that bind biogenic amines and neuropeptides © 2013 Pearson Education, Inc.

G Protein-Linked Receptors: Mechanism • Neurotransmitter binds to G protein–linked receptor • G protein

G Protein-Linked Receptors: Mechanism • Neurotransmitter binds to G protein–linked receptor • G protein is activated • Activated G protein controls production of second messengers, e. g. , Cyclic AMP, cyclic GMP, diacylglycerol, or Ca 2+ © 2013 Pearson Education, Inc.

G Protein-Linked Receptors: Mechanism • Second messengers – Open or close ion channels –

G Protein-Linked Receptors: Mechanism • Second messengers – Open or close ion channels – Activate kinase enzymes – Phosphorylate channel proteins – Activate genes and induce protein synthesis © 2013 Pearson Education, Inc.

Figure 11. 21 Indirect neurotransmitter receptor mechanism: G protein–linked receptors. Slide 1 Recall from

Figure 11. 21 Indirect neurotransmitter receptor mechanism: G protein–linked receptors. Slide 1 Recall from Chapter 3 that G protein signaling mechanisms are like a molecular relay race. Ligand (1 st Receptor messenger) G protein Enzyme 1 Neurotransmitter (1 st messenger) binds and activates receptor. 2 nd messenger Adenylate cyclase Closed ion channel Open ion channel Receptor G protein 5 a c. AMP changes membrane permeability by opening or closing ion channels. 5 c c. AMP activates specific genes. 5 b c. AMP activates GDP 2 Receptor activates G protein. © 2013 Pearson Education, Inc. 3 G protein activates adenylate cyclase. 4 Adenylate cyclase converts ATP to c. AMP (2 nd messenger). enzymes. Active enzyme Nucleus

Figure 11. 21 Indirect neurotransmitter receptor mechanism: G protein–linked receptors. Slide 2 Recall from

Figure 11. 21 Indirect neurotransmitter receptor mechanism: G protein–linked receptors. Slide 2 Recall from Chapter 3 that G protein signaling mechanisms are like a molecular relay race. Ligand (1 st Receptor messenger) G protein Enzyme 2 nd messenger 1 Neurotransmitter (1 st messenger) binds and activates receptor. Receptor Nucleus © 2013 Pearson Education, Inc.

Figure 11. 21 Indirect neurotransmitter receptor mechanism: G protein–linked receptors. Slide 3 Recall from

Figure 11. 21 Indirect neurotransmitter receptor mechanism: G protein–linked receptors. Slide 3 Recall from Chapter 3 that G protein signaling mechanisms are like a molecular relay race. Ligand (1 st Receptor messenger) G protein Enzyme 2 nd messenger 1 Neurotransmitter (1 st messenger) binds and activates receptor. Receptor G protein GDP 2 Receptor activates G protein. © 2013 Pearson Education, Inc. Nucleus

Figure 11. 21 Indirect neurotransmitter receptor mechanism: G protein–linked receptors. Slide 4 Recall from

Figure 11. 21 Indirect neurotransmitter receptor mechanism: G protein–linked receptors. Slide 4 Recall from Chapter 3 that G protein signaling mechanisms are like a molecular relay race. Ligand (1 st Receptor messenger) G protein Enzyme 1 Neurotransmitter (1 st messenger) binds and activates receptor. 2 nd messenger Adenylate cyclase Receptor G protein GDP 2 Receptor activates G protein. © 2013 Pearson Education, Inc. 3 G protein activates adenylate cyclase. Nucleus

Figure 11. 21 Indirect neurotransmitter receptor mechanism: G protein–linked receptors. Slide 5 Recall from

Figure 11. 21 Indirect neurotransmitter receptor mechanism: G protein–linked receptors. Slide 5 Recall from Chapter 3 that G protein signaling mechanisms are like a molecular relay race. Ligand (1 st Receptor messenger) G protein Enzyme 1 Neurotransmitter (1 st messenger) binds and activates receptor. 2 nd messenger Adenylate cyclase Receptor G protein GDP 2 Receptor activates G protein. © 2013 Pearson Education, Inc. 3 G protein activates adenylate cyclase. 4 Adenylate cyclase converts ATP to c. AMP (2 nd messenger). Nucleus

Figure 11. 21 Indirect neurotransmitter receptor mechanism: G protein–linked receptors. Slide 6 Recall from

Figure 11. 21 Indirect neurotransmitter receptor mechanism: G protein–linked receptors. Slide 6 Recall from Chapter 3 that G protein signaling mechanisms are like a molecular relay race. Ligand (1 st Receptor messenger) G protein Enzyme 1 Neurotransmitter (1 st messenger) binds and activates receptor. 2 nd messenger Adenylate cyclase Closed ion channel Open ion channel Receptor G protein 5 a c. AMP changes membrane permeability by opening or closing ion channels. GDP 2 Receptor activates G protein. © 2013 Pearson Education, Inc. 3 G protein activates adenylate cyclase. 4 Adenylate cyclase converts ATP to c. AMP (2 nd messenger). Nucleus

Figure 11. 21 Indirect neurotransmitter receptor mechanism: G protein–linked receptors. Slide 7 Recall from

Figure 11. 21 Indirect neurotransmitter receptor mechanism: G protein–linked receptors. Slide 7 Recall from Chapter 3 that G protein signaling mechanisms are like a molecular relay race. Ligand (1 st Receptor messenger) G protein Enzyme 1 Neurotransmitter (1 st messenger) binds and activates receptor. 2 nd messenger Adenylate cyclase Closed ion channel Open ion channel Receptor G protein 5 a c. AMP changes membrane permeability by opening or closing ion channels. 5 b c. AMP activates GDP 2 Receptor activates G protein. © 2013 Pearson Education, Inc. 3 G protein activates adenylate cyclase. 4 Adenylate cyclase converts ATP to c. AMP (2 nd messenger). enzymes. Active enzyme Nucleus

Figure 11. 21 Indirect neurotransmitter receptor mechanism: G protein–linked receptors. Slide 8 Recall from

Figure 11. 21 Indirect neurotransmitter receptor mechanism: G protein–linked receptors. Slide 8 Recall from Chapter 3 that G protein signaling mechanisms are like a molecular relay race. Ligand (1 st Receptor messenger) G protein Enzyme 1 Neurotransmitter (1 st messenger) binds and activates receptor. 2 nd messenger Adenylate cyclase Closed ion channel Open ion channel Receptor G protein 5 a c. AMP changes membrane permeability by opening or closing ion channels. 5 c c. AMP activates specific genes. 5 b c. AMP activates GDP 2 Receptor activates G protein. © 2013 Pearson Education, Inc. 3 G protein activates adenylate cyclase. 4 Adenylate cyclase converts ATP to c. AMP (2 nd messenger). enzymes. Active enzyme Nucleus

Basic Concepts of Neural Integration • Neurons function in groups • Groups contribute to

Basic Concepts of Neural Integration • Neurons function in groups • Groups contribute to broader neural functions • There are billions of neurons in CNS – Must be integration so the individual parts fuse to make a smoothly operating whole © 2013 Pearson Education, Inc.

Organization of Neurons: Neuronal Pools • Functional groups of neurons – Integrate incoming information

Organization of Neurons: Neuronal Pools • Functional groups of neurons – Integrate incoming information received from receptors or other neuronal pools – Forward processed information to other destinations • Simple neuronal pool – Single presynaptic fiber branches and synapses with several neurons in pool – Discharge zone—neurons most closely associated with incoming fiber – Facilitated zone—neurons farther away from incoming fiber © 2013 Pearson Education, Inc.

Figure 11. 22 Simple neuronal pool. Presynaptic (input) fiber Facilitated zone © 2013 Pearson

Figure 11. 22 Simple neuronal pool. Presynaptic (input) fiber Facilitated zone © 2013 Pearson Education, Inc. Discharge zone Facilitated zone

Types of Circuits • Circuits – Patterns of synaptic connections in neuronal pools •

Types of Circuits • Circuits – Patterns of synaptic connections in neuronal pools • Four types of circuits – Diverging – Converging – Reverberating – Parallel after-discharge © 2013 Pearson Education, Inc.

Figure 11. 23 a Types of circuits in neuronal pools. Input Many outputs ©

Figure 11. 23 a Types of circuits in neuronal pools. Input Many outputs © 2013 Pearson Education, Inc. Diverging circuit • One input, many outputs • An amplifying circuit • Example: A single neuron in the brain can activate 100 or more motor neurons in the spinal cord and thousands of skeletal muscle fibers

Figure 11. 23 b Types of circuits in neuronal pools. Input 1 Input 2

Figure 11. 23 b Types of circuits in neuronal pools. Input 1 Input 2 Input 3 Output © 2013 Pearson Education, Inc. Converging circuit • Many inputs, one output • A concentrating circuit • Example: Different sensory stimuli can all elicit the same memory

Figure 11. 23 c Types of circuits in neuronal pools. Input Output © 2013

Figure 11. 23 c Types of circuits in neuronal pools. Input Output © 2013 Pearson Education, Inc. Reverberating circuit • Signal travels through a chain of neurons, each feeding back to previous neurons • An oscillating circuit • Controls rhythmic activity • Example: Involved in breathing, sleep-wake cycle, and repetitive motor activities such as walking

Figure 11. 23 d Types of circuits in neuronal pools. Input Output © 2013

Figure 11. 23 d Types of circuits in neuronal pools. Input Output © 2013 Pearson Education, Inc. Parallel after-discharge circuit • Signal stimulates neurons arranged in parallel arrays that eventually converge on a single output cell • Impulses reach output cell at different times, causing a burst of impulses called an after-discharge • Example: May be involved in exacting mental processes such as mathematical calculations

Patterns of Neural Processing: Serial Processing • Input travels along one pathway to a

Patterns of Neural Processing: Serial Processing • Input travels along one pathway to a specific destination • System works in all-or-none manner to produce specific, anticipated response • Example – spinal reflexes – Rapid, automatic responses to stimuli – Particular stimulus always causes same response – Occur over pathways called reflex arcs • Five components: receptor, sensory neuron, CNS integration center, motor neuron, effector © 2013 Pearson Education, Inc.

Figure 11. 24 A simple reflex arc. Stimulus 1 Receptor Interneuron 2 Sensory neuron

Figure 11. 24 A simple reflex arc. Stimulus 1 Receptor Interneuron 2 Sensory neuron 3 Integration center 4 Motor neuron 5 Effector Spinal cord (CNS) Response © 2013 Pearson Education, Inc.

Patterns of Neural Processing: Parallel Processing • Input travels along several pathways • Different

Patterns of Neural Processing: Parallel Processing • Input travels along several pathways • Different parts of circuitry deal simultaneously with the information – One stimulus promotes numerous responses • Important for higher-level mental functioning • Example: a sensed smell may remind one of an odor and any associated experiences © 2013 Pearson Education, Inc.

Developmental Aspects of Neurons • Nervous system originates from neural tube and neural crest

Developmental Aspects of Neurons • Nervous system originates from neural tube and neural crest formed from ectoderm • The neural tube becomes CNS – Neuroepithelial cells of neural tube proliferate to form number of cells needed for development – Neuroblasts become amitotic and migrate – Neuroblasts sprout axons to connect with targets and become neurons © 2013 Pearson Education, Inc.

Axonal Growth: Finding the Target • Growth cone at tip of axon interacts with

Axonal Growth: Finding the Target • Growth cone at tip of axon interacts with its environment via: – Cell surface adhesion proteins (laminin, integrin, and nerve cell adhesion molecules or N-CAMs) which provide anchor points – Neurotropins that attract or repel the growth cone – Nerve growth factor (NGF) which keeps neuroblast alive • Once finds target must find right place to form synapse – Astrocytes provide physical support and cholesterol essential for construction of synapses © 2013 Pearson Education, Inc.

Figure 11. 25 A neuronal growth cone. © 2013 Pearson Education, Inc.

Figure 11. 25 A neuronal growth cone. © 2013 Pearson Education, Inc.

Cell Death • About 2/3 of neurons die before birth – If do not

Cell Death • About 2/3 of neurons die before birth – If do not form synapse with target – Many cells also die due to apoptosis (programmed cell death) during development © 2013 Pearson Education, Inc.