lecture 2 - neurobiology

NEUROBIOLOGY

CH.6

1 Biol340 - Mammalian Physiology

UNIT OUTLINE:

2 Biol340 - Mammalian Physiology

I.  INTRODUCTION i.  General Functions of Nervous System

II.  LEVELS OF ORGANIZATION

i.  Nervous System Divisions ii.  Protective Structures/Tissues iii.  Cell Types iv.  Classes of Neurons

III.  STRUCTURE & FUNCTION

i.  Membrane Potential ii.  Graded & Action Potentials iii.  Myelination iv.  Synapses

IV.  HOMEOSTASIS

i.  Regulation of Ion Channels ii.  Neurotransmitter Recycling iii.  Autonomic Division

V.  INTEGRATION

i.  Summation ii.  Circuits iii.  Clinical

UNIT LEARNING OUTCOMES: Student will be able to…

1.  Label the basic structural features of a generic neuron

2.  Compare & contrast the basic characteristics of the 3 functional classes of neurons

3.  Differentiate between the function and location of glial cell types.

4.  Compare the somatic and autonomic nervous systems.

5.  Contrast the characteristics (e.g. anatomy & neurotransmitters) of the parasympathetic and sympathetic systems.

6.  Explain the roles of CSF, meninges, and the blood brain barrier.

7.  Contrast the relative concentrations of ions in body solutions inside and outside of a cell (sodium, potassium, calcium and chloride ions).

8.  Explain how four factors determine a neuron’s resting membrane potential.

9.  Interpret a graph showing the voltage vs. time relationship of an action potential, and align this representation with the physical events in cell.

10.  Explain temporal and spatial summation of synaptic potentials and discuss how action potentials differ from synaptic potentials.

11.  List the events inside a neuron from activating input to neurotransmitter release.

12.  Classify simply neuronal circuits based on their characteristics and functional role.

13.  Describe how the nervous system maintains the environment around the neurons.

Biol340 - Mammalian Physiology 3

Remember that these Learning Outcomes make for a great basis for your studying. (Try turning the statements into questions.)

I. INTRODUCTION:

Functions of the Nervous System

•  Body’s primary communication and control system •  Integrates and regulates body functions •  Uses electrical activity

•  transmitted along specialized nervous system cells


I. INTRODUCTION: Nervous System Activities

•  Collects information •  specialized nervous structures, receptors •  monitor changes in external and internal environment, stimuli •  e.g., receptors in the skin detecting information about touch

•  Processes and evaluates information •  then determines if response required

•  Initiates response to information •  initiate response via nerves to effectors •  include muscle tissue and glands •  e.g., muscle contraction or change in gland secretion



II. LEVELS OF ORGANIZATION

General Topics – i.  Cells ii.  Divisions of Nervous System

i.  Afferent vs Efferent ii.  Autonomic Divisions

iii.  Brain & Spinal Cord Structure iv.  Barriers


STRUCTURE OF A NEURON II. LEVELS OF ORGANIZATION



FUNCTIONAL CLASSES OF NEURONS

Afferent neurons A.  Transmit info to the CNS from receptors at their peripheral endings. B.  Single processes from the cell body splits into a long peripheral

process (axon) that is in the PNS and a short central process (axon) that enters the CNS

Efferent neurons A.  Transmit out of the CNS to effector cells. B.  Cell body with multiple dendrites and a small segment of

the axon are in the CNS; most of the axon is in the PNS.

Interneurons A.  Function as

integrators and signal changers

B.  Integrate groups of afferent & efferent neurons into reflex circuits.

C.  Lie entirely within the CNS

D.  Account for >99% of all neurons



GLIAL CELLS MOST NUMEROUS CELLS IN THE CNS

Neurolemmocyte in the PNS •  Can myelinate only 1 mm

of single axon •  Takes many to myelinate

entire axon •  Gaps between

neurolemmocytes •  neurofibril nodes, or

nodes of Ranvier

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

PNS

Neurolemmocytes

Axon

(a) Myelination by neurolemmocytes

Neurofibril node

Myelin sheath Neurilemma

Neuron cell body



Oligodendrocyte in the CNS

•  Can myelinate 1 mm of many axons

•  Extensions wrapping around axons

•  No neurilemma formed •  Neurofibril nodes between

adjacent“wraps”

CNS

Oligodendrocytes

(b) Myelination by oligodendrocytes

Myelin sheath

Neurofibril node

Axons





The Nervous System has two major divisions:

•  The Central Nervous System (CNS), which is composed of the brain and spinal cord.

•  The Peripheral Nervous System (PNS) is composed of the nerves that connect the brain or spinal cord with the body’s muscles, glands, and sense organs.

The neuron is the basic cell type of both systems.



II. LEVELS OF ORGANIZATION Bone serves to support and to protect the structures of the CNS and PNS.

Cranium & Vertebrae Meninges are the membranes that line the structures and add additional support and protection.

Dura mater, Arachnoid mater & Pia mater

Blood-Brain Barrier

•  This is a protective mechanism that helps maintain a stable environment for the brain. •  Substances in the brain’s capillaries are separated from the extracellular space by the continuous endothelium of the capillary walls and a thick basal lamina surrounding the capillaries. The “feet” of the astrocytes surrounding the capillaries also contribute. •  These capillaries are the least permeable ones in the body. This barrier is very selective. Things that are highly lipid-soluble cross easily.





ANS VS SNS



AUTONOMIC NERVOUS SYSTEM Parasympathetic Sympathetic

Short pre-ganglionic & long post-ganglionic fibers. ACh at the pre-ganglionic synapse NE and Epi at the post-ganglionic synapse. “Flight or Fight” system.

Long pre-ganglionic & short post-ganglionic fibers. ACh at both pre- and post-ganglionic synapses. “Rest and Digest”system.

FIGURE 15.9


Sympathetic Pathways Parasympathetic Pathway

Preganglionic axon releases ACh.

Ganglionic neuron cell body and dendrites always contain receptors for ACh. Postganglionic axon releases ACh or NE.

Target cells contain either ACh receptors (bind ACh) or NE receptors (bind NE).

Target cell Target cell

(e.g., sweat glands and blood vessels in skeletal muscle)

Target cell (e.g., most other body structures)

Adrenergic receptors

NE

Nicotinic receptors

ACh ACh ACh

Nicotinic receptors

Nicotinic receptors

Muscarinic receptors

Muscarinic receptors

ACh ACh




If you were to prevent nicotinic acetylcholine receptors from functioning, what branch of the autonomic nervous system would be affected? A. Sympathetic B. Parasympathetic C. Both D. Neither

QUESTION



III. STRUCTURE & FUNCTION

General Topics – i.  Ionic concentrations ii.  Membrane potentials iii.  Ion channels iv.  Changes in membrane potentials v.  Myelination vi.  Synapses



BASIC PRINCIPLES OF ELECTRICITY


III. STRUCTURE & FUNCTION Don’t memorize the numbers, but do memorize the relationship!

[Na+] [Ca2+] [Cl-]

[K+] [protein-]

[Na+] [Cl-] [Ca2+]

[K+] [protein-]



In a resting neuron, A. The plasma membrane is freely permeable to sodium ion B. The concentration of sodium ion is greater inside the cell than outside C. The permeability of the plasma membrane to potassium ion is about 50 times greater than its permeability to sodium ion D. The plasma membrane is completely impermeable to sodium ion E. None of the choices are true

QUESTION



THE RESTING MEMBRANE POTENTIAL



ESTABLISHING THE RESTING MEMBRANE POTENTIAL There is a greater flux of K+ out of the cell than Na+ into the cell. •  This is because in a resting membrane there are a greater

number of open K+ channels than there are Na+ channels. Because there is greater net efflux than influx of positive ions during this step, a significant negative membrane potential develops, with the value approaching that of the K+ equilibrium potential.

In the steady-state, the flux of ions across the membrane reaches a dynamic balance. •  Because the membrane potential is not equal to the

equilibrium potential for either ion, there is a small but steady leak of Na+ into the cell and K+ out of the cell.

The concentration gradients do not dissipate over time, however, because ion movement by the Na+/K+-ATPase pump exactly balances the rate at which the ions leak through open channels.

28


Terminology

Biol340 - Mammalian Physiology



QUESTION In your work for a pharmaceutical company, you have just created a chemical that opens K+ channels in neurons. A neuron under the influence of this chemical will _____.

a.  be more likely to fire an action potential b.  be less likely to fire an action potential c.  The drug will have no effect on action potential firing.



DEPOLARIZATION



Graded potentials are changes in membrane potential that are confined to a relatively small region of the plasma membrane.

They are called graded potentials simply because the magnitude of the potential change can vary (is “graded”).

Graded potentials are given various names related to the location of the potential or the function they perform; for instance, receptor potential, synaptic potential, and pacemaker potential.

GRADED POTENTIALS

PROPAGATION OF ACTION POTENTIAL: DEPOLARIZATION Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Depolarization: Consecutive voltage-gated Na+ channels go through the following stages: open, closed (inactivation state), closed (resting state)

As threshold is reached Na+ channels open and Na+

diffuses in; polarity reversed

+ + + + + + + + + + + + + + – – – – – – – + + + + + + + + +

– – – – – – – – – – – – – – – – – – – + + +

Closed (resting state)

Cytosol

Interstitial fluid Na+

Closed (resting state)

Closed (inactivation

state)

Open (activation state)

–70 mv

–55 mv

+30 mv



PROPAGATION OF ACTION POTENTIAL: REPOLARIZATION Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

K+

Repolarization: Consecutive voltage-gated K+ channels go through the following stages: open and closed

K+ channels open and K+ diffuses out; RMP (–70 mv) is reestablished

–70 mv

+ + + + + + + + + + + + + + – – – – – – – – – + + + + + + + +

– – – – – – – – – – – + + + + + + + – – – – – – – – +30 mv

Closed Closed Open





MECHANISM OF AN ACTION POTENTIAL



REFRACTORY PERIOD



ACTION POTENTIAL PROPAGATION

VELOCITY OF A NERVE SIGNAL

Factors influencing velocity of nerve signal •  Diameter of axon

•  larger diameter, faster the velocity of the signal •  Myelination of axon

•  more important factor •  faster velocity in myelinated axons



VELOCITY OF A NERVE SIGNAL: PROPAGATION

Continuous conduction •  Occurs in unmyelinated axons •  Sequential opening of voltage-gated Na+ and K+ channels

Saltatory conduction •  Occurs in myelinated axons •  Action potentials propagated only at neurofibril nodes •  Myelinated regions

•  with limited numbers of voltage gated Na+ and K+ channels •  well insulated, preventing ion movement

•  Neurofibril nodes •  with large number of voltage-gated Na+ and K+ channels •  lack myelin insulation





SALTATORY CONDUCTION

Myelination •  Process by which part of an axon wrapped in myelin •  Myelin, insulating covering around axon

•  consists of repeating layers of glial cell plasma membrane

•  has high proportion of lipids •  gives glossy appearance and insulates axon

•  Completed by neurolemmocytes (PNS) •  Completed by oligodendrocytes (CNS)



(2) Neurolemmocyte cytoplasm and plasma membrane begin to form consecutive layers around the axon as wrapping continues.

(1) Neurolemmocyte starts to wrap around a portion of an axon.

Axon Neurolemmocyte

Direction of wrapping

Nucleus

(3) The overlapping inner layers of the neurolemmocyte plasma membrane form the myelin sheath.

Cytoplasm of the neurolemmocyte

Myelin sheath

Neurilemma

Neurolemmocyte nucleus

Myelin sheath

(4) Eventually, the neurolemmocyte cytoplasm and nucleus are pushed to the periphery of the cell as the myelin sheath is formed.



Myelination Process


1

2

TE

M 6

0,00

0x

Neurolemmocyte Unmyelinated axons

Neurolemmocyte

(a) (b)

Neurilemma

Myelinated axon

Myelin sheath

Unmyelinated axons Neurolemmocyte starts

to envelop multiple axons.

The unmyelinated axons are enveloped by the neurolemmocyte, but there are no myelin sheath wraps around each axon.

Unmyelinated axon

Axons

Neurolemmocyte nucleus

b: © Donald Fawcett/Visuals Unlimited Unmyelinated axons Associated with neurolemmocytes No myelin sheath covers them Axon in depressed portion of neurolemmocyte Not wrapped in repeated layers In CNS, unmyelinated axons not associated with oligodendrocytes





Synapses are junctions between two neurons.

Type:

•  Chemical

•  Pre-synaptic neurons release neurotransmitter from their axon terminals. The neurotransmitter binds to receptors on post-synaptic neurons.

•  Electrical.

•  Pre- and post-synaptic cells are connected by gap junctions, and the electrical activity of the “pre” effects the “post”.



Which of the following is the most common type of synapse?

A.  presynaptic dendrite to postsynaptic axon

B.  presynaptic axon to postsynaptic dendrite

C.  presynaptic axon to postsynaptic soma

D.  postsynaptic axon to presynaptic dendrite

QUESTION



MECHANISMS OF NEUROTRANSMITTER RELEASE

PHYSIOLOGIC EVENTS IN THE NEURON SEGMENTS: RECEPTIVE SEGMENT

Generation of EPSPs • Sequence of events

1)  Excitatory neurotransmitter crosses synaptic cleft. •  binds to receptor •  opens a chemically gated cation channel

2) More Na+ moves into neuron than K+ moves out. 3) Inside becomes slightly more positive.

•  less negative state called excitatory postsynaptic potential (EPSP)

4)  Local current of Na+ becomes weaker •  decreases in intensity with distance traveled



RELEASE OF EXCITATORY NEUROTRANSMITTER & GENERATION OF EPSP Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Release of excitatory neurotransmitter and generation of EPSP

Excitatory neurotransmitter released from presynaptic neuron binds to receptors, which are chemically gated cation channels, causing them to open.

1

2

Inside of neuron becomes more positive (less negative); called EPSP (e.g., –68 mV).

3

EPSP propagates toward axon hillock.

4

Excitatory neurotransmitter Postsynaptic neuron

Volt

age

(mV

)

Axons of presynaptic neuron

Postsynaptic neuron


Synaptic knob

Synaptic vesicles containing excitatory neurotransmitter

Time (msec)

Chemically gated cation channel

Na+ flows into neuron.

Na+

–80

–70

–60

–40

–20

0

EPSP Threshold

Resting membrane potential

Stimulus

Synaptic cleft (a) Biol340 - Mammalian Physiology 51


PHYSIOLOGIC EVENTS IN THE NEURON SEGMENTS: RECEPTIVE SEGMENT

Generation of IPSPs • Sequence of events

1)  Inhibitory neurotransmitter crosses synaptic cleft. •  binds to chemically gated K+ channel or Cl- channel •  depends on neurotransmitter and channels present

2)  If neurotransmitter binds K+ channel, K+ moves out of neuron. If neurotransmitter binds Cl-channel, Cl- flows into neuron.

3) Inside of the cell becomes slightly more negative •  more negative state termed inhibitory postsynaptic potential

(IPSP) 4) Local current of ions becomes weaker.

•  decreases in intensity with distance traveled toward initial segment



RELEASE OF INHIBITORY NEUROTRANSMITTER & GENERATION OF IPSP Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Release of inhibitory neurotransmitter and generation of IPSP

Inside of neuron becomes more negative; called IPSP (e.g., –72 mV).

3

2 Either K+ flows out of, or Cl–

flows into, the neuron, depending on the type of channel stimulated.

Inhibitory neurotransmitter binds to either chemically gated K+

channels or chemically gated Cl– channels, causing them to open. 1

K+

4


Synaptic vesicles containing inhibitory neurotransmitter

Inhibitory neurotransmitter Postsynaptic neuron

Chemically gated K+ channel

Chemically gated Cl– channel

Volt

age

(mV

)

Time (msec)

–80

–70

–60

–40

–20

IPSP

Threshold

Resting membrane potential

Stimulus

0

IPSP propagates toward axon hillock.

Cl–

Cl–

(b)




IV. HOMEOSTASIS

General Topics – i.  Control of Ion Channels ii.  Neurotransmitter Recycling iii.  Autonomic Division


IV. HOMEOSTASIS

Control Mechanisms of an Action Potential


IV. HOMEOSTASIS

Neurotransmitter Recycling

AUTONOMIC TONE

Most organs innervated by both divisions of ANS •  Termed dual innervation •  Stimulating continuously to varying degrees

•  referred to as autonomic tone •  E.g., diameter of most blood vessels in a partially constricted state

•  due to sympathetic tone •  Decrease in stimulation below tone

•  causes vessel dilation •  Increase above sympathetic tone

•  causes greater vessel constriction


IV. HOMEOSTASIS

DUAL INNERVATION Antagonistic Effects

•  Parasympathetic and sympathetic effects usually antagonistic •  E.g., control of heart rate

•  parasympathetic stimulation slowing heart rate •  sympathetic stimulation increasing heart rate •  same cells with both muscarinic and adrenergic receptors

•  E.g., control of muscular activity in GI tract •  parasympathetic stimulation accelerating rate of contraction and motility •  sympathetic stimulation decreasing motility •  same cells with both types of receptors

•  E.g., control of pupil diameter in the eye •  parasympathetic stimulation of circular muscle layer of iris

•  causes pupil constriction •  sympathetic stimulation of radial muscle layer of iris

•  causes pupil dilation •  different effectors innervated


IV. HOMEOSTASIS

SYSTEMS CONTROLLED ONLY BY SYMPATHETIC DIVISION

Opposing effects without dual innervation •  E.g., blood vessels innervated by sympathetic axons only

•  cause increased smooth muscle contraction and blood pressure •  vasodilation achieved by decreasing stimulation below

autonomic tone •  E.g., sweat glands in the trunk and arrector pili muscles in the

skin •  cause sweating and “goosebumps”

•  E.g., neurosecretory cells of adrenal medulla •  release epinephrine and norepinephrine, prolonging fight-or-

flight effects


IV. HOMEOSTASIS


V. INTEGRATION

General Topics – i.  Summation of Inputs ii.  Basic Circuits iii.  Clinical Applications

SEVERAL PRESYNAPTIC NEURONS WITH A POSTSYNAPTIC NEURON Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

SEM

80,

000x

IPSP EPSP Presynaptic

axons Synaptic

knob Postsynaptic

neuron


Dendrites


Myelin sheath

Cell body of postsynaptic neuron

Axon Simultaneous release Excitatory and inhibitory neurotransmitters may be simultaneously released from different neurons Varied frequency of releasing neurotransmitter Result: many EPSPs, many IPSPs, or both Biol340 - Mammalian Physiology 61

V. INTEGRATION

SPATIAL SUMMATION AT THE AXON HILLOCK


Initial segment

Axon hillock

Axons of presynaptic neurons (P), (P1–P5)

EPSPs

P2

P3

P4 P5

P1

Dendrites M

emb

ran

e p

oten

tial

(mV

)

Spatial summation

Action potential

Threshold

+30

0

–55

–70

Time (m sec)

P1 P2 P3 P4 P5

Myelin sheath

Axon

Cell body of postsynaptic neuron


V. INTEGRATION

TEMPORAL SUMMATION AT THE AXON HILLOCK


Axon of presynaptic neuron (P2)

P2

Axon EPSPs

Temporal summation

P2

Mem

bra

ne

pot

enti

al (m

V)

Action potential

Threshold

+30

0

–55

–70 Time (m sec)

Postsynaptic neuron


V. INTEGRATION

SYNAPTIC INTEGRATION


V. INTEGRATION


V. INTEGRATION


V. INTEGRATION

Simple circuits

Clinical View: Nervous System Disorders Affecting Myelin

•  Multiple Sclerosis •  progressive demyelination of neurons in CNS

•  autoimmune disorder •  oligodendrocytes attacked by immune cells •  repeated inflammatory events causing scarring and permanent loss of function •  vision problems, muscle weakness and spasms, urinary and bladder problems, mood

problems

•  Guillain-Barre syndrome •  loss of myelin from peripheral nerves due to inflammation •  muscle weakness that begins in distal limbs •  advances to involve proximal muscles •  no specific infectious agent identified

•  most function recovered with little medical intervention


V. INTEGRATION

Clinical View: Autonomic Dysreflexia •  Causes blood pressure to rise profoundly •  Stimulates a sympathetic reflex

•  causes systemic vasoconstriction •  marked increase in blood pressure

•  Caused by hyperactivity of ANS after a spinal cord injury •  Initial response to injury is spinal shock, with loss of autonomic reflexes •  Abnormal response to lack of innervation, denervation hypersensitivity

•  e.g., involuntary relaxation of internal urethral sphincter •  due to spinal cord reflex


V. INTEGRATION

lecture 2 - neurobiology

Documents

nervous system divisions

divisions of nervous

nervous system activities

nervous structures

autonomic nervous systems

control system

autonomic divisions

information initiate