Download doc Nerve and synapses

Nerve/Synapse
[“not a single atom that is in your body today was there when that event took place” – Steve Grand (computer scientist)]
-spinal cord=highway of processing information (relaying up to brain and down to
periphery of body) and mediates automated activities (ex. walking)
-afferent fibers or sensory neurons bring information from periphery to spinal cord (ex.
skin sensations)
-efferent fibers or motor neurons allow movement
-nervous system comprises about 100 billion neurons.
-neurons use electricity to propagate information from a place to another
-there is probably from a hundred trillion to a quadrillion of synapses in human nerv.syst.
∙soma: cell body, containing nucleus, where metabolic and
synthetic activities take place, maintaining neuron in living state
∙dendrites: “antennas” of neuron, for information to flow in
-axon: unique, for information to flow out (initial segment
inserts in cell soma, presynaptic terminal=swelling at axon’s
end)
Resting membrane potential: the inside of a neuron has a slightly negative voltage(=electrical pressure) compared to the outside (-60mV to -70mV,
tiny fraction of unpaired negatives charges, less than 1%). Neurons use it as a starting point for propagating electrical signals.
[almost all cells have a resting membrane potential]
-at rest, neurons still have great
permeability to potassium ions
(because of leak potassium channels),
but Ca&others can’t flow in nor out.
-negative voltage of neurons is then due to high
concentration of potassium ion
-When the chemical and electrical gradients are equal, the
system is at equilibrium(quickly attained). The membrane
potential at equilibrium is described by the Nernst equation.
-Nernst equation tells us exactly what the voltage is going to be
W/ the Nernst equation, we find E(Na)=+50mV and E(Cl)=-70mV
The resting membrane potential is a bit more positive than EK, because there is a small inward leak of Na+, which pushes the membrane slightly
toward ENa.
-The membrane potential is determined by concentration gradients and relative permeabilities of membrane to different physiological ions.
-The dominant permeability makes greatest contribution to the membrane potential. (At rest, the dominant permeability is to potassium, so the
membrane potential is close to EK.)
-Action potential is a jump in membrane potential, from negative to positive compared to the outside (all or none event).
-Three types of channels:
•leak potassium channels
•voltage-gated sodium channels
•voltage-gated potassium channels (accelerate falling phase, open w/ depolarization of axon, open slowly)
-These flows don’t change very much ions concentration (too small numbers), sodium-potassium pump are continuously in action (maintaining
gradients in background).
-Since the action potential always start at initial segment,
it always goes from initial segment down to presynaptic
terminal (inactivation of sodium channels).
[if you stimulate presynaptic terminal, action potential will
go up to soma, middle of axon: both directions]
-Action potential have same size and duration: differences are encoded in terms of frequency and pattern.
Sodium channels are the molecular targets for numerous naturally occurring neurotoxins:
•Puffer fish make tetrodotoxin, an extremely potent inhibitor of sodium channels.
•Phyllobates frogs secrete batrachotoxin, a powerful sodium channel activator.
•Sodium channels are also modulated by pyrethroid insecticides, as well as scorpion and anemonae toxins.
Sodium channels are blocked by therapeutically important drugs, including local anesthetics and some antiepileptic agents:
•Local anesthetics
•Antiepileptics
Lidocaine
Phenytoin (Dilantin)
Benzocaine
Carbamazepine (Tegretol)
Tetracaine
Lamotrigi
Cocaine
Rapid propagation of action potentials is important for survival, especially in situations that require rapid, reflexive responses. In squids, evolution
solved the problem of how to send fast-moving signals from one end of the body to the other by making giant axons, 1000 times fatter than our axons.
This strategy works because the propagation rate of the action potential is proportional to axon diameter.
Vertebrate neurons solve the problem of how to make a small axon with a high conduction velocity by wrapping the axon in an insulator called myelin.
Myelin is formed by Schwann cells (in the PNS) or oligodendrocytes (in the CNS).
-metaphor speed skater vs runner (push and glide
vs step by step) or people handing sandbags
(close to each other or tossing from a distance)
-Multiple sclerosis is cause by loss of myelin.
-white matter: regions of nervous system
containing large bundle of myelinated axons
-grey part is composed of cell bodies, dendrites
and synapses
-Axon is unique but has many embranchments.
-Botox & tetanus toxins chews up some of proteins
invovled in this process (so vesicle don’t fuse w/
membrane anymore), black widow venom makes vesicles
fuse spontaneously w/ membrane.
-excitatory synapses are only found on spines, inhibitory
synapses are found on dendrites shafts or soma
-The main excitatory neurotransmitter in the brain is
glutamate (amino acid), the most prevalent neurotransmitter
in nervous system.
-The EPSP is a small, transient depolarization of the
postsynaptic spine (1 to 2 mV and about 20 msec).
-From 50 to 100 EPSPs must sum at the initial segment to
initiate an action potential. These near-simultaneous EPSPs
can come from multiple synapses acting in synchrony and/or
from individual synapses, activated at high frequencies.
NMDA receptors will only conduct calcium if:
-activated by glutamate
-postsynaptic spine already depolarized
They are then coincidence receptors
-Long-term potentiation (LTP) is a model of synaptic
plasticity.
-High frequency activity depolarizes postsynaptic
spine, removing Mg2+ block of NMDA receptors and
enabling them to conduct Ca2+.
-EPSPs are larger, hours after induction of LTP. (more
AMPA receptors inserted into postsynaptic spine)
-Excitotoxicity is likely to contribute to neuronal
degeneration after stroke and in
neurodegenerative diseases.
.
-Epilepsy is caused by an imbalance of excitation
over inhibition.
-GABAA receptors are potentiated by a variety of drugs, including benzodiazepines (e.g. xanax), barbiturates (e.g. pentobarbital) and ethanol.
-Glutamate synapses have both ionotropic receptors (AMPA and NMDA receptors) and metabotropic glutamate receptors (mGluR’s)
-Glutamate makes mGluR change shape. That leads to a biochemical event inside of the cell which generates the formation of small soluble molecules
(2nd messenger).
-2nd messengers activate a range of cellular proteins, including ion channels, protein kinases and transcription factors.
-Glutamate&GABA activate both ionotropic& metabotropic receptors.
-Many types of neurotransmitters interact mainly or entirely with
metabotropic receptors. These substances, such as dopamine, serotonin
and norepinephrine, as well as neuropeptides like substance Y and
endorphins, are often referred to as neuromodulators. They are not
directly involved in the fast flow of neural information, but modulate
global neural states, influencing alertness, attention and mood.
-Neuromodulator systems are important targets for a wide range drugs.
For example, antidepressants, such as Prozac, affect serotonergic
transmission, whereas amphetamines, cocaine and other stimulants
typically affect dopamine and norepinephrine transmission.
-Axoaxonic synapses modulate neurotransmitter release from the
presynaptic terminal.
-Most of inhibitory neurons have short axons and most of excitatory have long axons.