Transcript on micro principles

Micro-Neuroscience
Daniel Ohngemach and Michael Putman
Neurons and Glia

Cells of the Nervous
System are divided into
two types:
Neurons are specialized
to transmit information in
the form of electrical
signals.
 Glia serve more diverse
roles:

Myelination (Schwann
Cells, Oligodendrocytes)
 Nourishment (Astrocytes)

Neuron Structure



Neurons exhibit two distinct features- the soma and
neurites.
The soma, or cell body, is functionally equivalent to
that of any other cell, but is differentiated to support
neuronal activity.
There are two major classes of neurites- dendrites,
which receive signals, and axons, which transmit
signals.
cell body
The Axon




The axon is a long and thin
extension of the cell
membrane (and cytosol).
The composition of the axonal
membrane and cytoplasm is
different than the rest of the
cell.
The Axon begins at the axon
hillock, and can branch in
multiple directions, ending at
an axon terminal.
Important molecules are
transported to the terminal
via axoplasmic transport
(along microtubules).
Biological Membranes



Cell membranes are
composed mostly of
phospholipids (bilayer).
The distinguishing feature
of a membrane are its
embedded proteins.
Many of these are integral
membrane proteins:




Channels
Receptors
Connectors
Etc.
Channel Proteins


Ungated Ion channels allow for
unregulated flow of ions down
concentration gradients.
Gated channels regulate ion flow:



Voltage Gated- controlled by
changes in membrane’s electrical
potential.
Ligand gated- controlled by
binding of a chemical.
The Sodium-Potassium Pump moves
ions against gradients.
Resting Membrane Potential
(RMP)





Various ion channels work in
concord to generate an electrical
potential across the membrane.
RMP in most human neurons: -65
mV.
The RMP is a result of Na+/K+
concentrations.
High concentration of Na+
outside the cell causes negatively
charged ions to line up alone the
inside of the membrane.
K+ concentration inside the cell is
kept high by the Na+/K+ pump
(also keeps Na+ concentration
outside the cell high).
Action Potential (AP)
1.
2.
3.
4.
5.
6.
Nearby membrane is depolarized;
voltage-gated Na+ channels open
(“Threshold”).
Na+ ions flood the local axon.
Electrical Potential across
membrane goes from RMP (-65
mV) to 32 mV.
Voltage-gated Na+ channels
inactivate; voltage-gated K+
channels activate. K+ ions flow
out of axon.
Membrane becomes
hyperpolarized (<-65 mV)- high
concentration of Na+ inside, K+
outside.
Na+/K+ pump restores RMP.
Synapses

Synapses fall into two
major categories:
 Electrical
Synapsescreated by physical
connections between
cells (Gap Junctions).
 Chemical Synapsesopen space (“synaptic
cleft”) bridged by
chemical
neurotransmitters.
Synaptic Transmission


“Presynaptic Neuron” transmits an
impulse to “Postsynaptic” Neuron
Presynaptic axon stores
neurotransmitters in vesicles in the
axon terminal. Neurotransmitter
release is triggered by an influx of
Ca++ ions, which cause
neurotransmitter-containing vesicles
to fuse with the membrane of the
axon terminal.


Postsynaptic membrane contains
receptors- proteins which bind
neurotransmitters and effect a
response.
Excess neurotransmitter release from
the presynaptic axon is either
recovered by the presynaptic cell or
degraded enzymatically.
Receptors

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Effect of a neurotransmitter
depends on the action taken by
the receptor.
Each receptor recognizes/binds
a unique neurotransmitter (only
1!).
A receptor agonist (e.g. nicotine)
mimics a neurotransmitter and a
receptor antagonist (e.g. curare)
inhibits the receptor’s behavior.
Two main types of receptor:

Ligand-gated ion channels allow
ion flow when they bind
neurotransmitters.

G-protein coupled receptors activate a
second messenger, which may open ion
channels or have some other effect.
Neurotransmitters
Amino Acids
Biogenic Amines
Proteins
Other
Glutamate
Dopamine
Substance P
Acetylcholine
GABA
Epinephrine
Norepinephrine
Serotonin
ATP
Amines

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Dopamine is involved in the brain’s reward
system (reinforces good behaviors), and can
lead to drug addiction.
Epinephrine release causes sympathetic
activation (“fight or flight”).
Norepinephrine is thought to increase the brain’s
responsiveness to stimuli (involved in attention,
sleep, and a host of other systems).
Serotonin is the major neurotransmitter affecting
mood and emotional behavior.
Dopamine
Epinephrine
Serotonin
Norepinephrine
Amino Acids


Glutamate is the major
excitatory neurotransmitter
of the brain- most
commonly used to trigger
Excitatory Postsynaptic
Potentials (EPSPs).
Gamma-aminobutyric acid
(GABA) is the major
inhibitory neurotransmitter
of the brain- most
commonly used to trigger
Inhibitory Postsynaptic
Potentials (IPSPs).
Proteins



Peptide
neurotransmitters are
larger than others- this is
thought to lead to
slower release time.
Many are not used for
direct neuron-neuron
communication, but have
other effects.
Substance P is a peptide
neurotransmitter that is
essential in the
regulation of pain.
Substance P
Other Neurotransmitters


Acetylcholine (Ach) is the main neurotransmitter at the
neuromuscular junction (also exhibits effects in the
brain).
Adenosine Triphosphate (ATP) is often found packaged
in vesicles with other neurotransmitters, and is thought to
enhance the effects of any given neurotransmitter.
ATP
Diffuse Modulatory Systems



Small centers within the brain
are responsible for overall
concentration of given
neurotransmitters.
Diffuse Modulatory neurons
often synapse with over
100,000 other neurons.
As an example: Raphe nuclei,
responsible for serotonin
levels, are often found to be
somewhat dysfunctional in
many patients with clinical
depression. Treatment often
involves drugs known as
Selective Serotonin Reuptake
Inhibitors (SSRIs).
Motor Control



Muscle is innervated
by alpha motor
neurons.
Alpha motor neurons
receive input directly
from the spinal cord.
Each alpha motor
neuron innervated
several muscle fibers.
The Neuromuscular Junction

Excitation-Contraction Coupling:
1.
2.
3.
4.
ACh is released from alpha
motor neuron, generating an
action potential on the
sarcolemma.
AP travels across sarcolemma
and down transverse tubules.
AP activates voltage-regulated
Ca++ channels in t-tubules.
T-tubule Ca++ channels are
linked to large Ca++ release
channels in the sarcoplasmic
reticulum (SR), which stores
large quantities of Ca++.
When depolarized, release
channels allow a large efflux
of Ca++ into the cytosol of
the muscle fibers.
Muscle Contraction
Major steps of
contraction:

1.
2.
3.
4.
5.
Ca++ binds to troponin,
exposing binding sites on
actin.
Myosin “heads” bind to
the exposed sites on
actin.
Binding causes myosin to
“pivot.”
ATP hydrolysis provides
energy to break myosinactin bonds.
Cycle repeats- myosin
“walks” down actin.
Memory



Memory is thought to be stored as neural circuitrythe path of impulse transmission.
Certain pathways are favored by increased
conductance of a neuron when activated by a
certain neurotransmitter.
Synaptic Plasticity: certain presynaptic-postsynaptic
relationships are favored, mostly by an
increased/decreased concentration of receptors in
the postsynaptic membrane.
Memory: A Closer Look

One molecular mechanism of
synaptic plasticity that is
understood very well is
AMPA/NMDA receptor
augmentation.
1.
2.
Glutamate binds to
postsynaptic receptors,
leading to both
ionotropic/metabotropic
effects.
Second messengers can
cause increased expression
of receptor protein genes.
Ions can activate protein
kinases, activating receptors
and causing them to be
incorporated into the
postsynaptic membrane.