1. Non-neuronal cells in the CNS (glia):
10-100x more abundant
Macroglia: large non-neuronal cells
1. astrocytes (star shaped) –
mostly located near axons and dendrites
WHY ???
Functions: a. insulate axons/dendrites (non-myelin sheath)
b. Provide many nutrients for neurons
c. “Astrogliosis”: engulf damaged neurons,
degrade them. “glial scar” at injury site
d. Help neurons become “excited” by
releasing potassium (K+) under certain
conditions

2. Oligodendrocytes: “oligo”… (few dendrites)
- found everywhere near neurons
Main functions: INSULATION !!
form myelin sheath
called “Schwann cells” in peripheral NS
called oligodendrocytes in CNS
Radial Glia:
Radial glial cells act as guide wires for the migration of neurons
- long processes,
very important for
development of brain
in embryos/fetuses
Targets of many substances (ex. alcohol)
that are “teratogens”
Nature Reviews:
Neuroscience, 2,

3. 4. Ependymal Cells:
- line walls of cerebral ventricles, make/secrete CSF
- projections (flagella) extend into ventricles and “flutter”
to produce motion of CSF so it will leave ventricle
Rabbit lateral ventricl
Adapted from Haines, D.E. Neuroanatomy: An atlas of structures, sections, and systems, 5th ed. Lippincott Williams & Wilkins, Baltimore, 2000

4. WHY DO WE NEED TO KNOW THIS ?!!!!!!!!!!!!!
Neural activity: how a neuron works
(1) physical properties of neuronal membrane
(2) presence of ion channels (or receptors) in membrane
(3) electrical potential across the membrane
WHY DO WE NEED TO KNOW THIS ?!!!!!!!!!!!!!
(1) neurophysiology correlates with behavior
for many clinical disorders
(2) neurophysiology can produce treatments
cell body - axon - dendrites
Definitions:
“Ion”: a molecule that unequal # of electrons and protons?
- molecule has positive (+) or negative (-) charge
“Electrical Potential”: difference in concentration of “+” and
“-” charged moleculars inside vs outside neuron
Important Ions: Sodium (Na+), Calcium (Ca2+), Potassium (K+),
chloride (Cl-)

5. How neurons communicate:
Neurons communicate by means of an electrical signal called the “Action Potential”
Action Potentials are based on movements of ions between the outside and inside of the cell
When an Action Potential occurs a chemical message is sent to neighboring neurons
Action potential is an electrical event inside of a single neuron
-involves movement of ions in or out of neuron
“Neurotransmission” is chemical communication between 2 or more
- involves a neuron release a “neurotransmitter” to contact
a nearby neuron(s)

6. The Neuron Membrane

7. Neurotransmitter receptors
Physical Properties of Membrane
Outside
Inside
* lipid bilayer- provides control of what gets in
not permeable to water or most
anything else.
-exceptions ?
2. non-rigid
ion channels
Neurotransmitter receptors

8. open only in specific situations
Properties of Ion Channels and Receptors:
1) proteins
extend from extracellular to intracelluar
2) highly specific for particular ions
3) opening and closing are tightly regulated
open only in specific situations
Electrical Potential Across Membrane:
* difference in + vs - charge from
outside to inside of cell
recording electrode
reference electrode
axon
extracellular fluid

9. Cell Membrane “at rest”
Outside of Neuron K+
Na+
Cl-
Ca2+
Cell Membrane “at rest” K+
Na+
Cl- -
Ca2+
Inside of Neuron
Potassium: more inside than outside
Sodium: more outside than inside
Chloride: more outside than inside
Calcium: more outside than inside
Negatively (-) charged
Proteins
- Lots of these !!!

10. ***** Negative Resting Potential *****
Expressed in “milliVolts (mV)”
what is the potential ?
- 70 mV
Large negatively charged
proteins
why is it negative ?
resting potential is close to
potential needed to “fire” = neurotransmitter release
How does it stay near the resting potential ?
Potassium equilibrium potential
Na-K+ exchanger
Inward rectifying K+ channels and Ca2+ channels ?
Most ions only get into a neuron if a membrane receptor or ion
channel open, don’t flow across neuron membrane freely…
1 ion does flow in and out of neuron along its
“concentration gradient” : ion easily crosses membrane according

11. Neurons don’t want most ions to flow across the concentration
gradient because that would cause constant electrical activity and
eventual neuron death…

12. 1. K+ equilibrium potential: only K+ flows across membrane
according to the concentration
gradient
*** Other ions only get in when receptors
or channels are forced open
At rest, more K+ outside of cell – so K+ wants to flow out to equalize intra- and extracellular concentrations.
But, as K+ flows out of cell, inside becomes more negative (because of large intracellular proteins). This negative charge attracts K+
remember, opposites attract !!
So, the resting membrane potential represents the balance between
1. K+ wanting to flow out of cell because of concentration gradient
2. negative proteins attracting K+ to stay in cell

13. So, why doesn’t this Na outflow make inside even more negative ??
2. Na-K+ exchanger: some sodium (Na) does leak into the cell, at all times.
So, neurons have a “pump” that pushes Na+ back out of the cell when concentrations get too high (which can happen in a matter of minutes)
So, why doesn’t this Na outflow make inside even more
negative ??
K+ comes in through the same pump that ejects Na
3. Inward “rectification” of K+ levels:
“K+ channels that primarily allow K+ in cells only under specific conditions…”
-serve a very specific function, maintaining the membrane at rest.

14. A neuron either is more or less likely to fire
What Happens when the potential is changed ?
A neuron either is more or less likely to fire
(1) Depolarizing stimulus - reduced potential
at -50 mV, Action Potential
what drives the action potential ?
Na+ channels open for milliseconds
at +40 mV, these close
K+ outflow repolarizes the potential * small undershoot

15. How does the action potential have an effect ?
where does this occur ??
cell body
axon
dendrites
Axon hillock
How does the action potential have an effect ?
propagation- action potential progresses down
the cell membrane by segments.
one region is stimulated, then the region next to it is, etc.
electrical current changes shape of
channels in adjacent regions
* Na+ channels

16. Axonal properties of propagation: (1) voltage-sensitive Na+ channels
(2) where are these Na+ channels ?
Axon (magnified)
myelin
nodes of Ranvier
saltatory conduction- “jumping”

17. At rest the inside of the cell is at -70 mV
With inputs to dendrites inside becomes more positive
if resting potential rises above threshold an action potential starts to travel from cell body down the axon
Figure shows resting axon being approached by an AP
Dr. Wayne Shebilske
Wright State University

18. Depolarization ahead of AP
AP opens cell membrane to allow sodium (NA+) in
inside of cell rapidly becomes more positive than outside
this depolarization travels down the axon as leading edge of the AP
Dr. Wayne Shebilske
Wright State University

19. Repolarization follows
After depolarization potassium (K+) moves out restoring the inside to a negative voltage
This is called repolarization
Dr. Wayne Shebilske
Wright State University

20. Finally, Hyperpolarization
Repolarization leads to a voltage below the resting potential, called hyperpolarization
Now neuron cannot produce a new action potential
This is the refractory period
What else might cause a “hyperpolarization” ?
Dr. Wayne Shebilske
Wright State University

21. What happens when the current gets to the end of axon ?
electrical vs. chemical communication between neurons
Otto Loewi-
using isolated frog heart in physiological fluid
electric stimulation slowed it down
applied fluid to another frog heart
slowed it down A. B. C.
Ca2+
Ca2+
A. nerve impulse arrives at terminal
deforms voltage gates Ca2+ channels
B. Ca2+ flows in
microtubules attached to vesicles contract
vesicle fuse with terminal membrane
C. vesicles burst, release neurotransmitter in synaptic cleft

22. How does neurotransmitter release change membrane
potential of another cell ?
cell body
axon
dendrites
Presynaptic terminal ends at a body, axon or dendrite
a receptor protein for NT must be present
1. excitatory post-synaptic potential (EPSP)
NT-receptor interaction causes small depolarization
Spatial Summation
Temporal Summation
-70 mV
-50

23. 2. inhibitory post-synaptic potential (IPSP)
NT-receptor interaction causes hyperpolarization
-70 mV
-50
Why an EPSP or an IPSP ?
1. neurotransmitter.
acetylcholine, dopamine, serotonin,
norepinephrine, glutamate, GABA
2. specific type of receptor
one neurotransmitter can produce
an EPSP or an IPSP, depending on receptor
EPSP IPSP
Na+ , Ca2+ or K Cl-

24. Either excitatory or inhibitory
Receptor can be an ion channel
binding site
Ionotropic Receptors are comprised of:
1. multiple subunits
different proteins link together
2. a core which is permeable to
one or a few ions
3. binding site on extracellular portion
characteristics:
fast acting
brief in duration
Either excitatory or inhibitory

25. Inhibitory Ionotropic Receptors: IPSP, Cl-
Drugs of abuse ???
ethanol - barbiturates - benzodiazepines
Excitatory Ionotropic Receptors : Na+, K+ ,Ca2+
- nicotine ?

26. Either excitatory or inhibitory
II. Metabotropic Receptors
G proteins
(guanine nucleotide binding)
Metabotropic Receptors are comprised of:
1. a single polypeptide binds to G proteins
3. binding site
1. G proteins “α” subunit “breaks off when NT binds”
activate second messengers , binds to other receptors,
binds to ion channels
Either excitatory or inhibitory
Characteristics:
slow acting
longer in duration

27. What happens to Neurotransmitter after Acting at Postsynaptic Site ?
1. enzymatic
breakdown
used to make
more NT
2. re-uptake by
transporter
reabsorbed by
vesicles
efficient - takes more energy to start over
essential amino acids
enzymatic processes
Serotonin (5-hydroxytryptamine or 5-HT)
reuptake is a major focus of drug development effort
WHY ??

28. Some peculiarities of actions potentials
Not all neurons “fire” at same potential ( -50 mV)
1. neurons with larger axons require less depolarization
-specialized to carry information more rapidly ??
2. some granule cells release small amounts of transmitter without having action potentials (do have small depolarization)
3. in some neurons, Na doesn’t drive the “spike” of the action potential- it’s Ca2+
Most action potentials last for less than ½ of a msec , but some action potentials are slow to develop and last minutes

29. 6. “Gap Junctions”- exceptions to the “chemical synapse”
Close physical contact
Electrical current decays
in cell 2
Current bi-directional
(usually)
4. Speed of transmission ?
Speed of response “
5. Where do you see these ?

30. Acetylcholine Serotonin Norepinephrine Dopamine Endorphins GABA
Neurotransmitters
Acetylcholine
Serotonin
Norepinephrine
Dopamine
Endorphins
GABA
Glutamate
Synthesized in neurons, stored in synaptic vesicles
Release by an Action Potential
Activate receptors on another neuron
on dendrites, soma, or axons

31. Acetylcholine (ACh) Found in “neuromuscular junction”
- here motor nerves touch muscle
Involved in muscle movements and
function of involuntary muscles
- breathing, heart muscle activity
Curare - blocks ACh receptors
paralysis results
Nerve gases and Black Widow spider venom - too much ACh leads to severe muscle spasms and possible death
Why are acetylcholine receptors important ??

32. Cigarettes - nicotine works on ACh receptors
can artificially stimulate skeletal muscles, leading to slight, trembling movements
Can also increase heart rate, breathing rate
Alzheimer’s Disease
Deterioration of memory, reasoning and language skills
Symptoms may be due to loss of ACh neurons

33. Where is it ? midbrain Basal forebrain pons medulla
Basal forebrain– sends axons to cortex, hippocampus
Cognition, judgement,
Reflexes, sensory processes

34. Serotonin (5-HT) Involved in sleep cause drowsiness
Involved in depression
SSRI’s (selective serotonin reuptake inhibitors) works by keeping serotonin in the synapse longer, giving it more time to exert an effect
Involved in sexual behavior
increasing serotonin in one
brainstem nucleus = loss of sexual
sensation

35. Where is it ? Raphe nuclei Raphe nuclei: project to thalamus
basal ganglia
hippocampus
cortex
Cognition, motor function, mood, sensory processing

36. Norepinephrine (NE) “Fight or flight” response
(aka. “adrenaline” )
“Fight or flight” response
released from adrenal gland
AND made by neurons
both a neurotransmitter and
a hormone
- any substance released by a gland into the bloodstream
Arousal = a brain stem nucleus
in “reticular formation” influences
your cogntive arousal

37. Where is it ? Locus coeruleus
Locus coeruleus – projects to basal ganglia
hippocampus
cortex
Cognition, memory, motor function…

38. Dopamine (DA) Involved in movement, attention and learning
Loss of dopamine- producing neurons is cause of Parkinson’s Disease
Dopamine imbalance also involved in schizophrenia
Required to experience “pleasure”
- “meso-limbic” DA system
Neurons in midbrain, send axons to forebrain (limbic system), release DA
Midbrain limbic system

39. Where is it ? Meso-limbo-cortical Mes-striatal
Meso-limbo-cortical: projects to nucleus accumbes
cortex
hippocampus
Drug reward, cognition, memory, sensory processes…
Meso-striatal: projects to striatum
Movement

40. - part of brains normal response to pain
Endorphins
- part of brains normal response to pain
Control pain and pleasure
Released in response to pain
Morphine and codeine work on endorphin receptors Involved in healing effects of acupuncture
Everywhere in the brain !!!

41. Gamma-Aminobutyric Acid (GABA)
Main inhibitory neurotransmitter
Benzodiazepines (which include tranquilizers such as Valium) and alcohol work on GABA receptor complexes
Everywhere in the brain !!

42. Glutamate Major excitatory neurotransmitter
Too much glutamate (and too little GABA) associated with epileptic seizures
Everywhere in the brain !!!
Very important for learning/memory

43. Hormones Chemical messengers secreted into bloodstream
Hormonal communication
Endocrine
cells
Blood-
stream
Target

44. Hormones vs. Neurotransmitters
Distance traveled between release and target sites
hormones travel longer distances (feet)
neurotransmitters - travel across a synaptic cleft (20 nm)
Speed of communication
hormones - slower communication
neurotransmitters - rapid, specific action

45. Hormones
Released by organs, including the stomach, intestines, kidneys and the even neurons
Also released by a set of glands called the endocrine system
Includes:
hypothalamus
pituitary gland
adrenal glands
thyroid gland
parathyroid glands
pineal gland
pancreas
ovaries and testes

46. Hypothalamus and Hormones
Hypothalamus releases releasing factors which in turn cause pituitary gland to release trophic hormones
“releasing hormone” = always from hypothalamus
“trophic hormone” = always from pituitary gland, causes
other glands to release hormones
- adrenal, ovaries, testes, thyroid, …
sexual maturation, sexual behavior, growth
of bones and soft tissue, water/salt balance, metabolism, breast feeding…