Fundamentals of the Nervous System and Nervous Tissue: Part E 11 Fundamentals of the Nervous System and Nervous Tissue: Part E

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

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)

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

Important Terminology Animation: Synapses Right-click slide / select “play”

Figure 11.16 Synapses. Axodendritic synapses Dendrites Axosomatic Cell body Axoaxonal synapses Axon Axon Axosomatic synapses Cell body (soma) of postsynaptic neuron

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

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

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

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

Synaptic Cleft Animation: Neurotransmitters Right-click slide / select “play”

Information Transfer Across Chemical Synapses AP arrives at axon terminal of presynaptic neuron Causes voltage-gated Ca2+ channels to open Ca2+ floods into cell Synaptotagmin protein binds Ca2+ and promotes fusion of synaptic vesicles with axon membrane Exocytosis of neurotransmitter into synaptic cleft occurs Higher impulse frequency  more released

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

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

Figure 11.17 Chemical synapses transmit signals from one neuron to another using neurotransmitters. Slide 1 Presynaptic neuron Presynaptic neuron Postsynaptic neuron Action potential arrives at axon terminal. 1 Voltage-gated Ca2+ channels open and Ca2+ enters the axon terminal. 2 Mitochondrion Ca2+ entry causes synaptic vesicles to release neurotransmitter by exocytosis 3 Synaptic cleft Axon terminal Synaptic vesicles Neurotransmitter diffuses across the synaptic cleft and binds to specific receptors on the postsynaptic membrane. 4 Postsynaptic neuron Ion movement Enzymatic degradation Graded potential Reuptake Diffusion away from synapse Binding of neurotransmitter opens ion channels, resulting in graded potentials. 5 Neurotransmitter effects are terminated by reuptake through transport proteins, enzymatic degradation, or diffusion away from the synapse. 6

Figure 11.17 Chemical synapses transmit signals from one neuron to another using neurotransmitters. Slide 2 Presynaptic neuron Presynaptic neuron Postsynaptic neuron Action potential arrives at axon terminal. 1 Mitochondrion Synaptic cleft Axon terminal Synaptic vesicles Postsynaptic neuron

Figure 11.17 Chemical synapses transmit signals from one neuron to another using neurotransmitters. Slide 3 Presynaptic neuron Presynaptic neuron Postsynaptic neuron Action potential arrives at axon terminal. 1 Voltage-gated Ca2+ channels open and Ca2+ enters the axon terminal. 2 Mitochondrion Synaptic cleft Axon terminal Synaptic vesicles Postsynaptic neuron

Figure 11.17 Chemical synapses transmit signals from one neuron to another using neurotransmitters. Slide 4 Presynaptic neuron Presynaptic neuron Postsynaptic neuron Action potential arrives at axon terminal. 1 Voltage-gated Ca2+ channels open and Ca2+ enters the axon terminal. 2 Mitochondrion Ca2+ entry causes synaptic vesicles to release neurotransmitter by exocytosis 3 Synaptic cleft Axon terminal Synaptic vesicles Postsynaptic neuron

Figure 11.17 Chemical synapses transmit signals from one neuron to another using neurotransmitters. Slide 5 Presynaptic neuron Presynaptic neuron Postsynaptic neuron Action potential arrives at axon terminal. 1 Voltage-gated Ca2+ channels open and Ca2+ enters the axon terminal. 2 Mitochondrion Ca2+ entry causes synaptic vesicles to release neurotransmitter by exocytosis 3 Synaptic cleft Axon terminal Synaptic vesicles Neurotransmitter diffuses across the synaptic cleft and binds to specific receptors on the postsynaptic membrane. 4 Postsynaptic neuron

ion channels, resulting in graded potentials. Figure 11.17 Chemical synapses transmit signals from one neuron to another using neurotransmitters. Slide 6 Ion movement Graded potential 5 Binding of neurotransmitter opens ion channels, resulting in graded potentials.

terminated by reuptake through transport proteins, enzymatic Figure 11.17 Chemical synapses transmit signals from one neuron to another using neurotransmitters. Slide 7 Enzymatic degradation Reuptake Diffusion away from synapse 6 Neurotransmitter effects are terminated by reuptake through transport proteins, enzymatic degradation, or diffusion away from the synapse.

Figure 11.17 Chemical synapses transmit signals from one neuron to another using neurotransmitters. Slide 8 Presynaptic neuron Presynaptic neuron Postsynaptic neuron Action potential arrives at axon terminal. 1 Voltage-gated Ca2+ channels open and Ca2+ enters the axon terminal. 2 Mitochondrion Ca2+ entry causes synaptic vesicles to release neurotransmitter by exocytosis 3 Synaptic cleft Axon terminal Synaptic vesicles Neurotransmitter diffuses across the synaptic cleft and binds to specific receptors on the postsynaptic membrane. 4 Postsynaptic neuron Ion movement Enzymatic degradation Graded potential Reuptake Diffusion away from synapse Binding of neurotransmitter opens ion channels, resulting in graded potentials. 5 Neurotransmitter effects are terminated by reuptake through transport proteins, enzymatic degradation, or diffusion away from the synapse. 6

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

Postsynaptic Potentials Neurotransmitter receptors cause graded potentials that vary in strength with Amount of neurotransmitter released and Time neurotransmitter stays in area

Table 11.2 Comparison of Graded Potentials and Action Potentials (1 of 4)

Table 11.2 Comparison of Graded Potentials and Action Potentials (2 of 4)

Table 11.2 Comparison of Graded Potentials and Action Potentials (3 of 4)

Table 11.2 Comparison of Graded Potentials and Action Potentials (4 of 4)

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

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

Figure 11.18a Postsynaptic potentials can be excitatory or inhibitory. +30 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. Membrane potential (mV) Threshold –55 –70 Stimulus 10 20 30 Time (ms) Excitatory postsynaptic potential (EPSP)

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

Figure 11.18b Postsynaptic potentials can be excitatory or inhibitory. +30 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. Membrane potential (mV) Threshold –55 –70 Stimulus 10 20 30 Time (ms) Inhibitory postsynaptic potential (IPSP)

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

Two Types of Summation Temporal summation Spatial 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

Figure 11.19a Neural integration of EPSPs and IPSPs. Threshold of axon of postsynaptic neuron Membrane potential (mV) Resting potential –55 –70 E1 E1 Time No summation: 2 stimuli separated in time cause EPSPs that do not add together. Excitatory synapse 1 (E1) Excitatory synapse 2 (E2) Inhibitory synapse (I1)

Figure 11.19b Neural integration of EPSPs and IPSPs. Threshold of axon of postsynaptic neuron Resting potential Membrane potential (mV) –55 –70 E1 E1 Time Temporal summation: 2 excitatory stimuli close in time cause EPSPs that add together. Excitatory synapse 1 (E1) Excitatory synapse 2 (E2) Inhibitory synapse (I1)

Figure 11.19c Neural integration of EPSPs and IPSPs. Threshold of axon of postsynaptic neuron Resting potential Membrane potential (mV) –55 –70 E1 + E2 Time Spatial summation: 2 simultaneous stimuli at different locations cause EPSPs that add together. Excitatory synapse 1 (E1) Excitatory synapse 2 (E2) Inhibitory synapse (I1)

Figure 11.19d Neural integration of EPSPs and IPSPs. Threshold of axon of postsynaptic neuron Membrane potential (mV) Resting potential –55 –70 l1 E1 + l1 Time Spatial summation of EPSPs and IPSPs: Changes in membane potential can cancel each other out. Excitatory synapse 1 (E1) Excitatory synapse 2 (E2) Inhibitory synapse (I1)

Integration: Synaptic Potentiation Repeated use of synapse increases ability of presynaptic cell to excite postsynaptic neuron Ca2+ concentration increases in presynaptic terminal and postsynaptic neuron Brief high-frequency stimulation partially depolarizes postsynaptic neuron Chemically gated channels (NMDA receptors) allow Ca2+ entry Ca2+ activates kinase enzymes that promote more effective responses to subsequent stimuli

Integration: Presynaptic Inhibition Excitatory neurotransmitter release by one neuron inhibited by another neuron via an axoaxonal synapse Less neurotransmitter released Smaller EPSPs formed

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

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 (AChE)

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

Classification of Neurotransmitters: Chemical Structure Amino acids Glutamate Aspartate Glycine GABA—gamma ()-aminobutyric acid

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

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 Ca2+ influx in astrocytes

Classification of Neurotransmitters: Chemical Structure Gases and lipids - gasotransmitters Nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide gases (H2S) 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 H2S acts directly on ion channels to alter function

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

Classification of Neurotransmitters: Function Great diversity of functions Can classify by Effects – excitatory versus inhibitory Actions – direct versus indirect

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

Classification of Neurotransmitters: Direct versus Indirect Actions Neurotransmitter binds to and opens ion channels Promotes rapid responses by altering membrane potential Examples: ACh and amino acids

Ion flow blocked Ions flow Ligand Closed ion channel Open ion channel Figure 11.20 Direct neurotransmitter receptor mechanism: Channel-linked receptors. Ion flow blocked Ions flow Ligand Closed ion channel Open ion channel

Classification of Neurotransmitters: Direct versus Indirect Actions Neurotransmitter acts through intracellular second messengers, usually G protein pathways Broader, longer-lasting effects similar to hormones Biogenic amines, neuropeptides, and dissolved gases

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 (1st messenger) Receptor G protein Enzyme 2nd messenger Neurotransmitter (1st messenger) binds and activates receptor. 1 Adenylate cyclase Closed ion channel Open ion channel Receptor G protein cAMP changes membrane permeability by opening or closing ion channels. 5a cAMP activates specific genes. 5c GDP cAMP activates enzymes. 5b Receptor activates G protein. 2 G protein activates adenylate cyclase. 3 Adenylate cyclase converts ATP to cAMP (2nd messenger). 4 Nucleus Active enzyme

Neurotransmitter Receptors Types Channel-linked receptors Mediate fast synaptic transmission G protein-linked receptor Oversee slow synaptic responses

Channel-Linked (Ionotropic) Receptors: Mechanism of Action Ligand-gated ion channels Action is immediate and brief Excitatory receptors are channels for small actions Na+ influx contributes most to depolarization Inhibitory receptors allow Cl– influx that causes hyperpolarization

Ion flow blocked Ions flow Ligand Closed ion channel Open ion channel Figure 11.20 Direct neurotransmitter receptor mechanism: Channel-linked receptors. Ion flow blocked Ions flow Ligand Closed ion channel Open ion channel

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

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 Ca2+

G Protein-Linked Receptors: Mechanism Second messengers Open or close ion channels Activate kinase enzymes Phosphorylate channel proteins Activate genes and induce protein synthesis

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 (1st messenger) Receptor G protein Enzyme 2nd messenger Neurotransmitter (1st messenger) binds and activates receptor. 1 Adenylate cyclase Closed ion channel Open ion channel Receptor G protein 5a cAMP changes membrane permeability by opening or closing ion channels. cAMP activates specific genes. 5c GDP cAMP activates enzymes. 5b Receptor activates G protein. 2 G protein activates adenylate cyclase. 3 Adenylate cyclase converts ATP to cAMP (2nd messenger). 4 Nucleus Active enzyme

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 (1st messenger) Receptor G protein Enzyme 2nd messenger Neurotransmitter (1st messenger) binds and activates receptor. 1 Receptor Nucleus

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 (1st messenger) Receptor G protein Enzyme 2nd messenger Neurotransmitter (1st messenger) binds and activates receptor. 1 Receptor G protein GDP Receptor activates G protein. 2 Nucleus

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 (1st messenger) Receptor G protein Enzyme 2nd messenger Neurotransmitter (1st messenger) binds and activates receptor. 1 Adenylate cyclase Receptor G protein GDP Receptor activates G protein. 2 G protein activates adenylate cyclase. 3 Nucleus

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 (1st messenger) Receptor G protein Enzyme 2nd messenger Neurotransmitter (1st messenger) binds and activates receptor. 1 Adenylate cyclase Receptor G protein GDP Receptor activates G protein. 2 G protein activates adenylate cyclase. 3 Adenylate cyclase converts ATP to cAMP (2nd messenger). 4 Nucleus

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 (1st messenger) Receptor G protein Enzyme 2nd messenger Neurotransmitter (1st messenger) binds and activates receptor. 1 Adenylate cyclase Closed ion channel Open ion channel Receptor G protein 5a cAMP changes membrane permeability by opening or closing ion channels. GDP Receptor activates G protein. 2 G protein activates adenylate cyclase. 3 Adenylate cyclase converts ATP to cAMP (2nd messenger). 4 Nucleus

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 (1st messenger) Receptor G protein Enzyme 2nd messenger Neurotransmitter (1st messenger) binds and activates receptor. 1 Adenylate cyclase Closed ion channel Open ion channel Receptor G protein 5a cAMP changes membrane permeability by opening or closing ion channels. cAMP activates enzymes. 5b GDP Receptor activates G protein. 2 G protein activates adenylate cyclase. 3 Adenylate cyclase converts ATP to cAMP (2nd messenger). 4 Nucleus Active enzyme

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 (1st messenger) Receptor G protein Enzyme 2nd messenger Neurotransmitter (1st messenger) binds and activates receptor. 1 Adenylate cyclase Closed ion channel Open ion channel Receptor G protein 5a cAMP changes membrane permeability by opening or closing ion channels. cAMP activates specific genes. 5c GDP cAMP activates enzymes. 5b Receptor activates G protein. 2 G protein activates adenylate cyclase. 3 Adenylate cyclase converts ATP to cAMP (2nd messenger). 4 Nucleus Active enzyme

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

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

Figure 11.22 Simple neuronal pool. Presynaptic (input) fiber Facilitated zone Discharge zone Facilitated zone

Types of Circuits Circuits Four types of circuits Patterns of synaptic connections in neuronal pools Four types of circuits Diverging Converging Reverberating Parallel after-discharge

Figure 11.23a Types of circuits in neuronal pools. Input 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 Many outputs

Figure 11.23b Types of circuits in neuronal pools. Input 1 Converging circuit • Many inputs, one output • A concentrating circuit • Example: Different sensory stimuli can all elicit the same memory Input 2 Input 3 Output

Figure 11.23c Types of circuits in neuronal pools. Input 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 Output

Figure 11.23d Types of circuits in neuronal pools. Input 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 Output

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

Figure 11.24 A simple reflex arc. Stimulus Interneuron 1 Receptor 2 Sensory neuron 3 Integration center 4 Motor neuron 5 Effector Spinal cord (CNS) Response

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

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