Glial cells
-support neurons structurally and metabolically (regulate pH, ion concentrations) e.g. Schwann cells and oligodendrites
-remove excess K+ from the extracellular fluid, prevent accumulation of extracellular K+ which would otherwise depolarize neurons
Neurons
-use a mixture of electrical and chemical signals to transmit information
-Excitable, i.e. electrical signals can be generated across plasma membrane
-Have passive and active electrical properties
Efferent neurons
carry signals from CNS to effector regions
Afferent neurons
carry signals towards CNS
Interneurons
complete neural circuit
The neural circuit
is the basic unit with which all animal nervous systems are built
anucleate neurons & ex.
-neurons with no nuclei
-Fairy wasps
Electric charge (q)
-measured in coulombs (C)
�The charge on a single electron is -1.6x10-19 C
�1 mol of electrons has a charge of -96,487 C, or 1 Faraday
Flow of electric charge
-current measured in amperes (A)
�A current of 1 C/sec is one Ampere
Electric potential or electromotive force
voltage measured in volts (V)
�Can be thought of as a measure of tendency for charges to flow
Resistance
measure of the impediment to current flow, measured in ohms (?)
�A resistance of 1 ? allows 1A of current to flow when a voltage of 1V exists
Ohm's law:
V=IR
Conductance
reciprocal of resistance (ease of current flow) measured in siemens (S)
Capacitance
measures ability of a nonconductor to store electric charge. Unit is the farad (F)
� a potential difference can build up across two plates separated by an insulator.
�No charges move across an insulator, but they can nonetheless interact with each other
membrane potential
-All neurons have a stable voltage or potential difference across their cell membrane
-measured by placing microelectrode inside cell and outside
-Voltage diff bt in and out ( -20 -100 mV)
-Cell interiors tend to be negatively charged
threshold potential
-critical number of Na+ channels open; Na+ floods into the neuron down its concentration gradient
- cell becomes rapidly positively charged / depolarized
-Ranges from -30mV to -50mV, but exact value depends on previous electrical activity inside the cell
Application of current in neurons can
-depolarize or hyperpolarize neurons depending on the direction of (+) current flow
-Na+ transport channels are voltage gated, and linked to the membrane potential - so as a cell becomes depolarized (i.e. less negative), those channels begin to open
action potential
- sudden spike in voltage
-Shortly after Na+ channels open, voltage-gated K+ channels open up
K+ rushes out of cell down its concentration gradient; cell becomes repolarized
delayed rectification
-repolarization of the cell after Na+ channels open
-Ion channels can be blocked by various drugs, e.g. tetrodotoxin
overshoot & undershoots
-Brief period of positivity in cell during AP
- After peaking, Vm goes back to resting value or even below
refractory period
During this period, impossible to generate another AP
insulator
-Lipid bilayer is impermeable to ions
- Consequently has properties of a capacitor, and can store charges on either side
-Ion channels that allow some particles to cross the membrane give it conductance/resistance
For a given transmembrane voltage (Vm)
-the lower the membrane resistance the more ions can cross the membrane through open ion channels per unit time
Membranes can act as ____?
capacitors by separating charges when a voltage is applied across the membrane
Ions can act _____?
-electrostatically with ions on the opposite side of the membrane
Because cell membrane is thin, charges can interact quite strongly
Capacitance of a membrane limits _____?
how fast the voltage across a membrane can change (because it takes time for charged particles to move)
electrochemical potential
is a Voltage difference across cell membranes
(Donnan equilibrium)
The charges of ions on either side of a membrane can maintain unequal concentrations by opposing the movement of similarly charged ions across the membrane
electromotive force (emf).
The force applied by the charges. is a measure of the work expended per unit of charge to produce an electric potential difference across a membrane
equilibrium potential
The potential difference maintained in this way (specifically for the ion which is able to cross the membrane)
Goldman equation
-takes into account all ion species and their relative permeabilities
-Probability that an ion will cross a membrane is proportional to the product of the concentration of the ion on one side and the permeability of the membrane to that type of ion
-This
Contribution of an individual ion to the overall membrane potential is?
proportional to its own concentration gradient across the membrane
-Vm is close to EK because the permeability of cell membranes to K+ is high
Electrogenic pump
asymmetrical exchange of Na+ and K+ ions gives rise to a potential difference across the cell membrane
relative refractory period
AP can be generated, but require much more intense stimulation than normal. Also, the amplitude of the AP will be less than normal
accomodation
If several stimuli are delivered in sequence, the membrane becomes progressively less excitable (i.e. threshold potential rises).
Phasic neurons _____?
exhibit accommodation
e.g. Pacinian corpuscles (mechanoreceptors in skin that sense vibration and pressure)
Tonic neurons
fire repeatedly, albeit with gradually reduced frequency
e.g. some olfactory neurons
adaptation
Reduction in frequency
Action potentials are an example of?
Limited by what 2 things?
-positive feedback
-1. the driving force (emf) on Na+ is reduced as Vm approaches ENa
-2. Na+ channels become automatically deactivated (closed) after a certain period of time
Hodgkins cycle
-cycle of channel opening and closing and flow of Na+ ions
Voltage clamping allowed Hodgkin and Huxley to?
-to depolarize a cell to a specific voltage and hold it there
-By bringing the cells to the equilibrium potential of the individual ions, able to measured the conductance of those ions across the membrane
- work out the charges on each membrane surface by
Patch clamping
allowed researchers to record the currents passing through individual ion channels
Tetrodotoxin (TTX)
enabled researchers to estimate the density of ion channels on a given membrane surface (because TTX binds to Na+ channels, so they radioactively labeled it)
Voltage gating is driven by
a conformational change in the ion channels themselves in response to the change in Vm, and the change in charge in particular
Molecular structure of K+ channels
Four alpha protein subunits, 4 beta protein subunits for channel modulation
Molecular structure of Na+ channels
Single large alpha protein with 4 membrane-linked domains
Ca2+ channels
-extremely similar to Na+
-Ca2+ important in crustacean neurons, vertebrate smooth muscle and cardiac muscle, embryonic neurons, synapses and dendrites
-Ca2+ channels are so ubiquitous, it is thought that APs were originally driven by Ca2+ rather than Na+
Passive signals are ?
electrotonic (degrade over distance)
For long-distance conduction, graded sensory
Graded signals must ?
- make it to the spike-initiating zone to become APs
Alternate APs and passive signals along the length of a neuronal circuit
synapses
Between neurons, signals are transferred across
Chemical synapses:
APs propagated along axons prompt release of neurotransmitters. These in turn cause a change in Vm in the postsynaptic membrane (dendrites and soma of the next neuron in the circuit). This is called a post-synaptic potential. This response is graded, but
Electrical synapses:
-Much faster than chemical synapses, but subject to signal attenuation
-Current can flow in either direction through an electrical synapse
-In rectifying synapses, current flows more readily in one direction
- Electrical synapse activity can be recorded b
Passive spread of signals depends on what 2 things?
-1.movement of positive charges (ions) along the two faces of the plasma membrane
-2. resistance and capacitance of the cell - called cable properties
-These properties affect the distance of signal conduction
Why plasma membranes are insulator?
-The cytoplasm generally has less resistance than plasma membranes
-Signals decrease because current (ions) leaks out of cell through plasma membrane
Distance of propagation depends on_____?
leakiness of plasma membrane, as well as cell and membrane resistance and capacitance
length constant
How far a signal can spread
non-spiking neurons
-neurons so small that generation of APs isn't possible
-Transmit signals entirely via passive, electrotonic potentials
-Must still rely on APs to ensure signal propagation
-Signals must still be large enough to elicit release of neurotransmitters
Short or absent axons
-high membrane resistance, and hence very high length constants.
-Highly efficient and undecremented spread of signals through these neurons.
- Found in places like the vertebrate retina
APs must be
- regenerated
- Vm in one region is transmitted electrotonically (i.e. passively) to a neighboring region
-Current produced by Na+ crossing the membrane spreads longitudinally through the axon, because entering positive charge pushes charges in cytosol aw
Electrotonic transmission is not directional, yet APs travel in one direction only - why?
Because of the refractory period following AP generation - remember that neurons become temporarily hyperpolarized because of K+ conductance, and that the Na+ channels become temporarily deactivated.
Consequently, membrane that has just produced an AP can
safety factor
-to ensure the AP signal makes it to the next site of AP generation even if signal decreases because of electrotonic transmission
- Total depolarization during AP is around 100mV
- Typical threshold potential about 20mV
AP produces signal boost of around
Speed of AP propagation depends on?
cable properties of cells
Speed increases under two conditions:
(1) Internal cell resistance decreases/cross sectional area increases. Many fast-conducting invertebrate neurons are very large e.g. squid giant axons
(2) Membrane resistance increases (i.e. greater insulation). Prevents current leaking out of cell. This
Myelinated cells wrapped in what? Explain two consequences of this.
- 200 layers of the cell membranes of glial cells (oligodendrites and Schwann cells)
-1. extra lipid layers increase resistance of the neuron membrane, enhance speed and efficiency of electronic signal transmission
- 2. decrease membrane capacitance (i.e.
Entire axon must be?
unmyelinated spaces (Nodes of Ranvier) where charges can move across the membrane so that APs can be regenerated
saltatory conduction
-APs "jump" from one node of Ranvier to the next
- Electrotonic signals spread rapidly through internodes which lack voltage-gated ion channels entirely
-Conduction speed of myelinated fibres ranges from a few meters per second to more than 120 m.s-1
-Unm
chemical synapses:(1) Fast or direct chemical transmission
- found in the neuromuscular junction and other places in the central nervous system.
-Release of synaptic vesicles via exocytosis into the synaptic cleft.
-Neurotransmitter molecules are very small.
chemical synapses:(2) Slow or indirect chemical transmission
-neurotransmitter release is the first of several steps that result in a change in Vm.
-Neurotransmitter molecules here are large, and synthesized from amino acids. Biogenic amines (single aa), neuropeptides (several aa).
-Postsynaptic response is slow, a
neuromuscular junction
- Where fast chemical synapses occur. Also called motor endplates or motor terminals
junctional folds
- Where Axons terminals lie in the muscle membrane
- Clusters of active zones above the folds in each membrane
Axon terminals innervating a single muscle fibre contain around
1 000 000 synaptic vesicles
Acetylcholine (ACh)
- diffuses into synaptic cleft down concentration gradient towards active zones
- Binds to ACh-specific receptors in the postsynaptic membrane of the neuromuscular junction, causing Na+ and K+ selective channels to open
ACh is then hydrolyzed by
acetylcholinesterase (AChE). This limits time during which ACh is active
endplate potential (epp)
Depolarization of motor endplate associated with ACh
Application of curare to neuromuscular junction
-prevents muscle from contracting
- binds ACh receptors
- reduces the magnitude of the epp to below threshold potential so no AP can be generated
postsynaptic current
The change in rate of ion flow across the postsynaptic membrane
miniature endplate potentials (mepps)
Spontaneous "miniature" depolarizations are found to occur near postsynaptic membrane at motor endplates,
quanta or individual vesicles
represent "units" of transmitter release
Quantal release
100-300 vesicles each containing around 10,000 neurotransmitter molecules typically released from axon terminals, which activate around 2000 postsynaptic channels.
Readily releasable pool
fraction of vesicles in axon terminal that are able to be released at a given time
Synaptic delay -
time taken for neurotransmitters to cross synaptic cleft and bind with active zones
Non-spiking release
some neurons which do not generate APs are nonetheless able to release neurotransmitter
SNAREs
Binding to postsynaptic membrane is mediated by proteins called
Fast direct:
-acetylcholine is excitatory at the sympathetic neuromuscular junction; gamma-aminobutyric acid (GABA) and glycine are inhibitory in the central nervous system; glutamate is excitatory in CNS. Neurons releasing ACh are called cholinergic
Slow indirect:
-act via secondary messengers within the cell called G-proteins. Biogenic amines (amino acid derivatives) include epinephrine, norepinephrine, dopamine, catecholamines and serotonin.
- Neurons releasing norepinephrine are called adrenergic. Neuropeptides
Nicotinic ACh receptors
-bind nicotine, are responsible for fast, direct neurotransmission
-Nicotinic receptors occur in neuromuscular junction.
-Permeable to both Na+ and K+; Erev somewhere in between ENa and EK
Antagonists
bind receptors and inhibit their action (e.g. curare).
Muscarinic ACh receptors
-bind muscarin (mushroom toxin)
- responsible for slow, indirect neurotransmission
electroplax organs
Muscarinic ACh is studied through theses organs of teleost fish
G-protein alpha subunit
Alpha portion binds guanosine diphosphate and guanosine triphosphate
-GDP bonds= inactive
- GTP bonds=active
Receptor binding causes GDP to be replaced with GTP
muscarinic receptors & G-proteins
tend to open K+ channels which hyperpolarize the cell and are thus inhibitory
Neuromodulation
-Slow indirect transmission takes longer, but much longer-lasting
- slow transmission can modulate effects of fast synaptic transmission
- slow transmitter neuromodulation can affect more than one target neuron
Presynaptic inhibition
1.reduces the amount of neurotransmitter released from excitatory neuron terminal
2.May increase conductance of K+ or Cl+ or render Ca2+ channels less responsive to depolarization
3.Net effect postsynaptic membrane receives less neurotransmitter
Alpha-motoneurons
any one signal is extremely small and often not enough to generate an AP by itself
Integration at synapses
-Each neuron integrates all input it receives (excitatory, inhibitory, slow and fast) from hundreds or thousands and will either fire to produce an AP or not
-Processes linking synaptic potentials are complex
-Depends on electrotonic spread of postsynapti
Inhibitory neurons tend to?
lie close to spike-initiating zone; are able to block excitatory signals effectively and ensure APs only fire when needed
Signals in dendrites and soma spread ? & Why is it important?
- electrotonically
- size of signal decreases with distance
-Location of synapses therefore important
-synapses further away from spike-initiating zone are less effective
summation
When several postsynaptic potentials add together to affect postsynaptic Vm,
spatial summation
when signals come from two or more different locations
Temporal summation
when high-frequency inputs occur at a specific rate. Successive potentials can "piggy-back" onto each other
Nervous system
-Nervous systems present in all animals
-Basic principles of neural function are the same in all taxa
central nervous system
-As nervous systems become more complex, neurons are compacted
- Within the CNS, cell bodies of neurons are placed in close proximity with each other, increasing opportunities for interconnections
reflex arc & 3 types
Basic pathway for information flow in the nervous system. Single cell, monosynaptic reflex, polysynaptic reflex
single cell
may be both receptor and effector neuron
Monosynaptic reflex arc
comprises a sensory nerve synapsing onto an effector
Polysynaptic reflex arc
includes one or more interneurons
Increasing number of interneurons ?
presents greater potential for behavioral complexity via intergration and neuromodulation
parallel processing & route of information
-permits the system to analyze information more rapidly than a linear fashion.
- convergence of information into clusters of neurons allows comparison and integration of information from various kinds of sensory input and from multiple processing areas of
comparative method
-method used to understand nervous system evolution, cannot be studied through the fossil record
Nervous system evolution based on____ ? & what trends?
- elaboration of the basic reflex arc
-Trend towards collection of neurons into CNS and ganglia
-Trend towards cephalization - grouping together of similar functional neurons in anterior part of body
-Relative size of brain regions in each species reflect
Spinal cord def. & segment regions
-major dorsal nerve cord in all vertebrates
1.cervical 2.thoracic 3. lumbar 4.sacral
a) white matter b) gray matter
a) after shiny white color of myelin sheaths on axons
b)contains soma and dendrites of interneurons and motor neurons
spinal canal
Fluid-filled central cavity in spinal cord
cerebrospinal fluid
continuous with that of the cerebral ventricles in the brain
Afferent neurons enter
CNS through dorsal roots
Efferent neurons carry information
out via ventral roots
1.ventral horn
2. dorsal horn
3.dorsal root ganglia
1. Soma of spinal motor neurons located in ventral gray matter
2. Soma of afferent neurons in dorsal gray matter
3. where sensory neurons synapse onto afferent interneurons
neural tube
-Forerunner of nervous system
-develops during gastrula-stage
-From this, three vesicles (precursors of fore-, mid- and hindbrain) develop,regions later subdivide further
Medulla oblongata
-where the brain joins spinal cord
-Contains centers controlling respiration and autonomic function
-Relays messages from sensory system (e.g. equilibrium and hearing)
- relays messages to motor centers
Cerebellum
-dorsal to medulla oblongata
-Pair of smooth (in lower vertebrates) or convoluted (in higher vertebrates) hemispheres
-Contributes to coordination of output
-Compares and integrates information from semi-circular canals and proprioceptors
-Controls postur
Pons
- a relay station
- consists of fiber tracts connecting different regions of the brain
-Contains tectum or optic lobe
Tectum
-receives and integrates visual input, but also auditory and tactile
-Information organized into "maps" from different modalities
Synaesthesia
modalities become confused (e.g. can see sounds as colors)
Thalamus
-a major coordinating center for both sensory and motor signalling
-Sensory information sent from thalamus to sensory regions of cerebral cortex
-Motor information received by thalamus from cortex as well
Amygdala
-processes information and organizes output relating to emotions
-It is linked to hypothalamus
hypothalamus
-includes centers controlling temperature regulation, thirst and appetite
- also involved in emotional responses such as excitement, pleasure and rage
Neuroendocrine cells
-inside hypothalamus control water and electrolyte balance, pituitary gland action
Olfactory region
- Anterior of brain
-especially large in those vertebrates that rely heavily on smell
- only sensory modality that is not processed through the hypothalamus in mammals, but rather travels directly to the cerebrum
Cerebral cortex
-Surface highly convoluted - increases surface area for neurons
-Surface gray matter organized into sublayers
-organized into functional regions (e.g. sensory, motor)
-In "higher" vertebrates, association regions are neither clearly sensory nor clearly mo
Autonomic nervous system
-sympathetic and parasympathetic
- When animal is relaxed or asleep, parasympathetic pathway is dominant
-When excited or frightened, sympathetic is dominant
Autonomic reflex arc
-processed in brain - otherwise afferent automatic reflexes identical to somatic
Efferent reflex arc
- motor output carried by chains of neurons