16 Nervous System 2 Physiology

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Nervous System 2

Physiology, Reflex Arc

LO 2 &3

Chapter 7
Figure 11.2
Neurophysiology
• Neurons have 2 functional properties:
1. Neurons are highly irritable (irritability):
Respond to a stimulus and convert it into a nerve impulse
2. Conductivity:
Ability to transmit impulse to other neurons, muscles and
glands

• Action potentials, or nerve impulses, are:


– Electrical impulses carried along the length of axons
– Always the same regardless of stimulus
– The underlying functional feature of the nervous
system
Electricity Definitions
• Voltage (V) – measure of potential energy
generated by separated charge
• Potential difference – voltage measured between
two points
• Current (I) – the flow of electrical charge between
two points
• Resistance (R) – hindrance to charge flow
• Insulator – substance with high electrical resistance
• Conductor – substance with low electrical
resistance
Electrical Current and the Body
• Reflects the flow of ions rather than
electrons
• There is a potential on either side of
membranes when:
– The number of ions is different across the
membrane
– The membrane provides a resistance to ion
flow
Role of Ion Channels
• Types of plasma membrane ion channels:
– Passive, or leakage, channels – always open
– Chemically gated channels – open with binding
of a specific neurotransmitter
– Voltage-gated channels – open and close in
response to membrane potential
– Mechanically gated channels – open and close
in response to physical deformation of receptors
Operation of a Gated Channel
• Example: Na+-K+ gated channel
• Closed when a neurotransmitter is not bound to the
extracellular receptor
– Na+ cannot enter the cell and K+ cannot exit the cell
• Open when a neurotransmitter is attached to the receptor
– Na+ enters the cell and K+ exits the cell
Operation of a Voltage-Gated Channel
• Example: Na+ channel
• Closed when the intracellular environment is negative
– Na+ cannot enter the cell
• Open when the intracellular environment is positive
– Na+ can enter the cell
Gated Channels and Gradients
• When gated channels are open:
– Ions move quickly across the membrane
– Movement is along their electrochemical gradients
– An electrical current is created
– Voltage changes across the membrane

• Ions flow along their chemical gradient when they move


from an area of high concentration to an area of low
concentration
• Ions flow along their electrical gradient when they move
toward an area of opposite charge
• Electrochemical gradient – the electrical and chemical
gradients taken together
Resting Membrane Potential (Vr)
• The potential difference (–70 mV) across the membrane of
a resting neuron
• It is generated by different concentrations of Na+, K+, Cl−,
and protein anions (A−)
• Ionic differences are the consequence of:
– Differential permeability of the neurilemma to Na+ and K+
– Operation of the sodium-potassium pump
Membrane Potentials: Signals

• Used to integrate, send, and receive information


• Membrane potential changes are produced by:
– Changes in membrane permeability to ions
– Alterations of ion concentrations across the
membrane
• Types of signals – graded potentials and action
potentials
Changes in Membrane Potential
• Changes are caused by three events
– Depolarization – the inside of the membrane
becomes less negative

– Repolarization – the membrane returns to its resting


membrane potential

– Hyperpolarization – the inside of the membrane


becomes more negative than the resting potential
Conduction Velocities of Axons
• Conduction velocities vary widely among
neurons
• Rate of impulse propagation is determined
by:
– Axon diameter – the larger the diameter, the
faster the impulse
– Presence of a myelin sheath – myelination
dramatically increases impulse speed
Saltatory Conduction
• Current passes through a myelinated axon only at the
nodes of Ranvier
• Voltage-gated Na+ channels are concentrated at these
nodes
• Action potentials are triggered only at the nodes and jump
from one node to the next
• Much faster than conduction along unmyelinated axons
Threshold and Action Potentials
• Threshold – membrane is depolarized by 15 to 20 mV
• Established by the total amount of current flowing
through the membrane
• Weak (subthreshold) stimuli are not relayed into action
potentials
• Strong (threshold) stimuli are relayed into action
potentials
• All-or-none phenomenon – action potentials either
happen completely, or not at all

• The CNS determines stimulus intensity by the frequency


of impulse transmission
Absolute Refractory Period
• Time from the opening of the Na+
activation gates until the closing of
inactivation gates
• The absolute refractory period:
– Prevents the neuron from generating an
action potential
– Ensures that each action potential is separate
– Enforces one-way transmission of nerve
impulses
Nerve Fiber Classification
• Nerve fibers are classified according to:
– Diameter
– Degree of myelination
– Speed of conduction
Synapses
• A junction that mediates information transfer from
one neuron:
– To another neuron
– To an effector cell
• Presynaptic neuron – conducts impulses toward
the synapse
• Postsynaptic neuron – transmits impulses away
from the synapse
Synapses

Figure 11.17
Types of Synapses
• Axodendritic – synapses between the axon
of one neuron and the dendrite of another
• Axosomatic – synapses between the axon
of one neuron and the soma of another
• Other types of synapses include:
– Axoaxonic (axon to axon)
– Dendrodendritic (dendrite to dendrite)
– Dendrosomatic (dendrites to soma)
Electrical Synapses

• Electrical synapses:
– Are less common than chemical synapses
– Correspond to gap junctions found in other
cell types
– Are important in the CNS in:
• Arousal from sleep
• Mental attention
• Emotions and memory
• Ion and water homeostasis
Chemical Synapses
• Specialized for the release and reception of
neurotransmitters
• Typically composed of two parts:
– Axonal terminal of the presynaptic neuron, which
contains synaptic vesicles
– Receptor region on the dendrite(s) or soma of
the postsynaptic neuron
Synaptic Cleft
• Fluid-filled space separating the presynaptic and
postsynaptic neurons
• Prevents nerve impulses from directly passing
from one neuron to the next
• Transmission across the synaptic cleft:
– Is a chemical event (as opposed to an electrical one)
– Ensures unidirectional communication between
neurons
Synaptic Cleft: Information Transfer
• Nerve impulses reach the axonal terminal of the
presynaptic neuron and open Ca2+ channels
• Neurotransmitter is released into the synaptic cleft via
exocytosis
• Neurotransmitter crosses the synaptic cleft and binds to
receptors on the postsynaptic neuron
• Postsynaptic membrane permeability changes, causing
an excitatory or inhibitory effect
Synaptic Cleft: Information Transfer

Figure 11.19
Termination of Neurotransmitter Effects
• Neurotransmitter bound to a postsynaptic neuron:
– Produces a continuous postsynaptic effect
– Blocks reception of additional “messages”
– Must be removed from its receptor
• Removal of neurotransmitters occurs when they:
– Are degraded by enzymes
– Are reabsorbed by astrocytes or the presynaptic
terminals
– Diffuse from the synaptic cleft
Postsynaptic Potentials
Synaptic Delay
• Neurotransmitter must be released, diffuse across the
synapse, and bind to receptors
• Synaptic delay – time needed to do this (0.3-5.0 ms)
• Synaptic delay is the rate-limiting step of neural
transmission
Postsynaptic Potentials
• Neurotransmitter receptors mediate changes in
membrane potential according to:
– The amount of neurotransmitter released
– The amount of time the neurotransmitter is bound to
receptors
• The two types of postsynaptic potentials are:
– EPSP – excitatory postsynaptic potentials
– IPSP – inhibitory postsynaptic potentials
Excitatory Postsynaptic
Potentials
• EPSPs are graded potentials that can
initiate an action potential in an axon
– Use only chemically gated channels
– Na+ and K+ flow in opposite directions at the
same time
• Postsynaptic membranes do not generate
action potentials
Neurotransmitters
• Chemicals used for neuronal
communication with the body and the
brain
• 50 different neurotransmitters have been
identified falling into 3 major categories
and 10 to 12 general types

• Classified chemically and functionally


Chemical Neurotransmitters
• Acetylcholine (ACh)
• Biogenic amines
• Amino acids
• Peptides
• Novel messengers: ATP and dissolved
gases NO and CO
Neurotransmitters: Acetylcholine
• First neurotransmitter identified, and best
understood
• Released at the neuromuscular junction
• Synthesized and enclosed in synaptic vesicles
• Degraded by the enzyme acetylcholinesterase
(AChE)
• Released by:
– All neurons that stimulate skeletal muscle
– Some neurons in the autonomic nervous
system
Neurotransmitters: Biogenic
Amines
• Include:
– Catecholamines – dopamine, norepinephrine
(NE), and epinephrine
– Indolamines – serotonin and histamine
• Broadly distributed in the brain
• Play roles in emotional behaviors and our
biological clock
Synthesis of Catecholamines
• Enzymes present in the
cell determine length of
biosynthetic pathway

• Norepinephrine and
dopamine are
synthesized in axonal
terminals

• Epinephrine is released
by the adrenal medulla

Figure 11.22
Neurotransmitters: Amino Acids
• Include:
– GABA – Gamma ()-aminobutyric acid
– Glycine
– Aspartate
– Glutamate
• Found only in the CNS
Neurotransmitters: Peptides
• Include:
– Substance P – mediator of pain signals
– Beta endorphin, dynorphin, and enkephalins
• Act as natural opiates, reducing our
perception of pain
• Bind to the same receptors as opiates and
morphine
• Gut-brain peptides – somatostatin, and
cholecystokinin
Neurotransmitters: Novel
Messengers
• ATP
– Is found in both the CNS and PNS
– Produces excitatory or inhibitory responses
depending on receptor type
– Induces Ca2+ wave propagation in astrocytes
– Provokes pain sensation
Neurotransmitters: Novel
Messengers
• Nitric oxide (NO)
– Activates the intracellular receptor guanylyl
cyclase
– Is involved in learning and memory
• Carbon monoxide (CO) is a main regulator
of cGMP in the brain
Functional Classification of Neurotransmitters
• Two classifications: excitatory and inhibitory
– Excitatory neurotransmitters cause depolarizations
(e.g., glutamate)
– Inhibitory neurotransmitters cause hyperpolarizations
(e.g., GABA and glycine)

• Some neurotransmitters have both excitatory and


inhibitory effects
– Determined by the receptor type of the postsynaptic
neuron
– Example: acetylcholine
• Excitatory at neuromuscular junctions with skeletal muscle
• Inhibitory in cardiac muscle
Neurotransmitter Receptor Mechanisms
• Direct: neurotransmitters that open ion channels
– Promote rapid responses
– Examples: ACh and amino acids
• Indirect: neurotransmitters that act through
second messengers
– Promote long-lasting effects
– Examples: biogenic amines, peptides, and dissolved
gases
Acetylcholine (Ach)
Channel-Linked Receptors
• Composed of integral membrane protein
• Mediate direct neurotransmitter action
• Action is immediate, brief, simple, and highly localized
• Ligand binds the receptor, and ions enter the cells
• Excitatory receptors depolarize membranes
• Inhibitory receptors hyperpolarize membranes
G Protein-Linked Receptors
• Responses are indirect, slow, complex,
prolonged, and often diffuse
• These receptors are transmembrane protein
complexes
• Examples: muscarinic ACh receptors,
neuropeptides, and those that bind biogenic
amines
G Protein-Linked Receptors: Mechanism
• Neurotransmitter binds to G protein-linked receptor
• G protein is activated and GTP is hydrolyzed to GDP
• The activated G protein complex activates adenylate cyclase
• Adenylate cyclase catalyzes the formation of cAMP from ATP
• cAMP, a second messenger, brings about various cellular
responses
Development of Neurons
• The nervous system originates from the
neural tube and neural crest
• The neural tube becomes the CNS
• There is a three-phase process of
differentiation:
– Proliferation of cells needed for development
– Migration – cells become amitotic and move
externally
– Differentiation into neuroblasts
Axonal Growth
• Guided by:
– Scaffold laid down by older neurons
– Orienting glial fibers
– Release of nerve growth factor by astrocytes
– Neurotropins released by other neurons
– Repulsion guiding molecules
– Attractants released by target cells
Reflexes
• A reflex is a rapid, predictable motor
response to a stimulus
• Reflexes may:
– Be inborn (intrinsic) or learned (acquired)
– Involve only peripheral nerves and the spinal
cord
– Involve higher brain centers as well
Reflex Arc
• There are five components of a reflex arc
– Receptor – site of stimulus
– Sensory neuron – transmits the afferent impulse to
the CNS
– Integration center – either monosynaptic or
polysynaptic region within the CNS
– Motor neuron – conducts efferent impulses from the
integration center to an effector
– Effector – muscle fiber or gland that responds to the
efferent impulse
A simple Reflex Arc
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