Transcript Neurons

Neurons
Functional Organization of Neurons
Input zone
(dendrites)
Transmission zone
(axon)
Output zone
(synapses)
The Resting Potential
• Almost all cells have a transmembrane
electrical charge difference, with the inside
roughly 50-100 mV negative relative to the
outside.
• Voltage = electrical driving force, reflecting
the energy required to separate charges –
so charge separation is a form of stored or
potential energy.
Electrical Energy and Chemical Energy Are
Interconvertable
• At electrochemical equilibrium, the chemical driving force
of an ionic gradient is exactly counterbalanced by the
gradient’s equilibrium potential. The mathematical
statement of this is the Nernst Equation, written here for
the K+ gradient:
V=RT/zF ln ([K+]out/[K+]in )
R: universal gas constant
T: temperature in deg. K
Z: ionic charge (+1 here)
F: Faraday’s number
At mammalian body temperature, each
additional order of magnitude of the
concentration ratio term of the Nernst Eq.
adds an additional 60 mV to the total
voltage – i.e. a 1/10 gradient gives -60
mV, a 1/100 gradient gives -120 mV, etc.
Concentration Gradients and Permeability
Properties Cause the Membrane Potential
• The membrane
potential arises from
the interaction of two
factors:
• Transmembrane ionic
concentration
differences
• Selective permeability
properties of the
membrane
[K+]=4Eq/l
[Na+}=145
mEq/l
[K+]=100m
Eq/l
[Na+]=15
mEq/l
You could think of the K+ gradient as “wanting” to drive +
charge to the outside of the cell and thus make it insidenegative; the Na+ gradient “wants” to do the opposite.
Na+ gradient:, corresponding to an equilibrium potential
of about +60 mV
K+ gradient: , corresponding to an equilibrium potential of
about -90 mV
K+ permeability/Na+ permeability = about 20X
Which ion wins?
Neither K+ nor Na+ wins entirely, but since the K+
gradient and the K+ permeability are both larger,
the outcome is an inside-negative potential.
Thus, The membrane potential is determined by
the relative magnitude of the concentration
gradients for Na+ and K+, weighted by their
permeabilities.
This is expressed in mathematical form by the
Goldman Equation
+
+
(PK[K ]out + PNa [Na ]out)
V=RT/F ln
(PK[K+]in + PNa [Na+]in)
Depolarization? Hyperpolarization?
• Depolarization =less inside-negative V =action
potentials more likely
–
–
–
–
–
–
Increase in extracellular [Na+]
Increase in extracellular [K+]
Decreased K+ conductance
Increased Na+ conductance
Excitatory synaptic input
Anything that causes a net inward flow of + charge
• Hyperpolarization: action potentials less likely
– Opposites of everything that causes depolarization
Action Potentials
• rapid, brief stereotypic changes in an
excitable cell’s membrane potential
• the method of rapid transmission of
information over long distances (>1mm).
Basic Characteristics of Action
Potentials
• Initiated by depolarization due to some
stimulus
• Require a minimum intensity/duration of
stimulus to be initiated (“threshold”)
• Are followed by a period of decreased
responsiveness (“refractory period”)
• Are conducted along the axon (or muscle
cell) without a decrease in magnitude
(“non-decremental conduction”)
Factors that determine conduction velocity
• Axon diameter: larger =
faster: you could think of
the surface/volume ratio of
the axon determining how
much current leaks out of
the axon versus how much
continues down the axon
core. The larger the
diameter, the more easily
current flows down the
core and the farther ahead
of itself the AP can reach
to depolarize fresh
membrane.
Myelination = faster conduction than unmyelinated axons of similar
diameter
Myelination is the result of wrapping of the axon by glial cells (Schwann
cells in the peripheral nervous system, oligodendrocytes in the CNS) –
the wrapping is interrupted periodically by Nodes of Ranvier. This leads
to saltatory conduction.
Chemical Communication at
Synapses: Steps
• AP arrives at synaptic terminal of presynaptic cell
• Ca++ entry triggers release of some vesicles of
transmitter chemical
• Transmitter diffuses across synaptic cleft
• Transmitter binds to receptors on surface of postsynaptic
cell
• Interaction of transmitter and receptor leads to temporary
change in postsynaptic cell’s probability of undergoing
an action potential – usually this involves a change in the
cell’s membrane potential – this change is called a postsynaptic potential (PSP).
Excitatory Synaptic Transmission
Depolarizing PSP spreads
through cell body by
decremental conduction. APs
generally cannot be initiated in
the cell body
PSP arrives at axon hillock or
initial segment considerably
diminished in magnitude. An
AP (or more than one) can
result if the axon hillock is
brought to threshold.
Integration of Synaptic Inputs
• Most CNS neurons are not “follower cells”
– instead, they integrate their synaptic
inputs, or add them up over time and
space. This is because PSPs summate
within the postsynaptic cell’s input
segment. The summation is algebraic,
because some synaptic inputs are
inhibitory.
Neurons can be decision-makers
A
Inputs A and B
form an “and”
gate
B
+
+
-
C
A B and C form a
comparator,
where the neuron
becomes active
only if A and B
are more
effective than the
inhibitory
synapse from C
In principle, all of the decisions that the NS
makes can be made by single neurons
integrating their inputs, but in the
vertebrate CNS virtually all decisions are
made by the interaction of dozens to
thousands of neurons.
At the whole-system level, we could define
“integration” as processing sensory
information for an appropriate response.
Reflexes – the simplest functional
responses of the NS
• Reflex: an immediate, brief, predictable
response to a stimulus
• Reflex arc consists of an afferent (sensory)
pathway, an integrating center, and an
efferent (motor) pathway that connects to an
effector.
• Reflexes frequently are involved in protecting or
restoring physiological values to their normal
ranges. Such stabilizing responses are termed
homeostatic.
Reflexes and negative feedback
Efferent pathway
Effectors
Set point
Error signal
Environmental
perturbation
sensors
Afferent
pathway
Integrating
Center
To translate this into terms of a real system,
core body temperature is closely regulated
by a negative feedback system. The sensors
of the system are thermosensory neurons
scattered about the thorax and abdomen.
The integrating center is in the
hypothalamus of the brain. The effectors
include neuromuscular pathways involved in
behavioral responses and shivering
thermogenesis, neurovascular pathways
that regulate blood flow to the body surface,
and pathways that regulate sweating and
piloerection.
Basic Characteristics of Negative
Feedback Systems
• System is reactive – it doesn’t respond
until after the regulated variable departs
from the setpoint.
• The gain of the system is defined as
departure from the setpoint with no
feedback / departure from the setpoint with
feedback operating.
For example, if a 10o difference
between ambient temperature and core
body temperature drives a 0.01o
decrease in core body temperature, the
gain of the body’s thermostat is 10/0.01
=1000.
So, the bottom-line statement about
negative feedback control is that such
systems tolerate a small amount of
variation around the setpoint while
preventing large departures from it.