Prelim 4 Biog1440 Flashcards
Types of Neurons
- Model Neuron
- Sensory Neuron (sensory nerve responds to chemical or physical stimuli)
- Motor neuron (originates from the central nervous system)
- Local interneurons (communicate between 2 neurons)
- Project interneuron
- Neuroendocrine cell (responsible for producing hormones and released into circulation)
Excitation
The cells are able to respond to a certain number or stimuli
Membrane Potential
The difference in charges between inside and outside a cell
Resting membrane potential
At resting state of a neuron, this membrane potential is negative (-65 millivolts)
When is the cell polarized?
The cell is polarized when anything that changes the resting membrane potential resulting from ion flow brings the resting membrane potential towards 0 or the positive side. Then the cell is capable of responding to a stimulus.
–> basis of excitation in the neuron
Sodium Potassium ATPase
For every 3 molecules of Na+ that moves outside, 2 molecules of K+ is brought into the cell through active transport
Intercellular and Extracellular values for K+, Na+, Cl-, and A-
K+ Intracellular: 140 Extracellular: 5 Na+ Intracellular: 15 Extracellular: 150 Cl- Intracellular: 10 Extracellular: 120 Large anions (A-) Intracellular: 100 Extracellular: Not applicable
Why is the overall charge negative?
The large anions give it the negative charge and thus, the negative membrane potential
Potassium channels (leak channels)
They are known as leak channels because they have a random switching rate between open and closed states to allow potassium to flow out of the cell
Sodium channels
Most of which are not really open, allow sodium to flow into the cell
Chemical force
The differentials in concentration between the extracellular and intracellular environment for the Na+ & K+ creates a concentration gradient. Diffusion would favor the neutralization of the number of molecules on both sides of the membrane, however, this asymmetry exists and this chemical force exist in parallel with electrical forces.
Electrical force
Attraction between opposite charges in an effort to remain neutral
ex. Works to keep K+ inside the cell. The net flow of K+ out of the neuron (which is natural because it wants to reach a state of equilibrium) should be kept in to stay neutralized. They do not want K+ to escape to the outside of the cell despite the K+ channels
ex. Na+ and Cl- are oppositely charged so they’re at equilibrium
The result of the electric force
No net flow across the membrane (able to maintain resting membrane potential at around -60). Also called the equilibrium potential
Nernst equation
E ion = 62(log [ion]out/[ion]in)
units in mV
For each ion, given that the concentration differs from outside vs. inside the cell…
There will be an electrical force that exactly balances the chemical force
Permeability of K+, Na+, and Cl-
K+>Na+>Cl-
Graded hyperpolarization
If the resting potential was to decrease or become more negative, the cells can become more resistant to stimuli. These are called the graded hyperpolarization and can occur if certain stimulus produces and increased membrane permeability to K+.
Graded depolarization
If the resting potential was to increase, then the cell can be more easily excited than these transient temporal shifts. These are called the graded depolarization that are produced by stimuli that increase membrane permeability to sodium (called graded potentials)
If the graded depolarization that brings an increase in sodium into the cell reaches a particular threshold…
The voltage-gated sodium channels will open and will result in an action potential. There is a huge influx of sodium.
What is the threshold in mV?
Voltage gated channels open when the resting membrane potential reaches the threshold, -55 mV
Steps of an Action Potential
Resting state: The gated Na+ and K+ channels are closed, Ungated channels maintain the resting potential (ligand gated channels and the Na+ K+ ATPase)
- A stimulus is necessary to trigger an action potential and the stimulus brings a change to the resting membrane potential
Depolarization: A stimulus opens some Na+ channels. Na+ inflow through those channels depolarizes the membrane. If the depolarization reaches the threshold, it triggers an action potential
Rising phase of the action potential: Depolarization opens most sodium channels while potassium channels remain closed. Na+ influx makes the inside of the membrane positive with respect to the outside
-Peak of the curve is when the Na+ channels begin to close and K+ channels open. There is a small delay even though they are activated at the same threshold.
Falling phase of the action potential: Most Na+ channels become inactivated, blocking Na+ inflow. Most K+ channels open, permitting K+ outflow, which makes the inside of the cell negative again.
Undershoot: The sodium channels close, but some potassium channels are still open. As these potassium channels close and the sodium channels become unlocked (though still closed), the membrane returns to its resting state (with the help of ligand-gated channels and the sodium potassium ATPase)
Speed of voltage gated channels
Voltage gated Na+ channels are quick to open and quick to close.
Voltage gated K+ channels are slow to open and slow to close
Importance of the undershoot and propagation of action potential
Due to a depolarization event occuring in one location, the location right adjacent to that is also activated. When the adjacent region is activated, the region that was previously excited is undergoing the undershoot so it is not able to activate again. This provides the directionality for the flow across an axon up the nerves
* Not possible for an action potential to go backwards
Structure of typical neurons and communication networks
The signal is received in the neuronal cell body, integrated in the axon hillock, communicated or transmitted through the axon, and then ends in the synaptic terminals, which might stimulate elicit specific function
Decay of an action potential
Depolarization across the membrane in one location can propagate passively along the axon, but the extent of depolarization decays with distance.
Two factors that dictate the decay of a depolarization event
1) Resistance across the membrane (depends on other open ion channels) - rm
2) Axial resistance within the cell (diameter) - ri
The larger the diameter, the lower the axial resistance, The larger the axon, the quicker the action potential
The depolarization that occurs in one membrane location can flow…
passively along the axon, but the extent of the decay that occurs to that signal across a particular distance because if it does not meet another voltage gated channel where the depolarization is still above the threshold, then it will fail to activate the next channel –> excitation is terminated
What continues the excitation?
The voltage-gated channels across the surface of the membrane
Calculated by lambda (the length constant)
Lambda
Corresponds to the distance where the potential has decreased to 37% & is calculated by:
the sqr root of rm/ri
Adaptations to continue the flow of the action potential
- Myelin sheath: insulation of the axonal regions by lipid bilayers
Myelination
Jump of action potentials from node to node
Insulation is done by the glial cells (there are two types)
Peripheral nervous system: Schwann cell
Central Nervous system: Oligodendrocytes
Insulation is when the axon is wrapped around by layers of lipid bilayer
Purposes of myelination
1) The wrapping of bilayer around the axon do not allow the flow of an action potential across that region, by doing this, they force the action potential to jump from node to node (nodes of Ranvier). This makes the action potential faster.
2) Increases membrane resistance so that ions do not flow out of the membrane (because of insulation). This allows you to carry the charge further.
Difference between Schwann and Oligodendrocyte
Schwann cells are in the peripheral nervous system and a single schwann cell will wrap around 1 axon, however, oligodendrocytes are in the CNS and wrap around multiple axons from different neurons in the same location
Nodes of Ranvier
Nodes are the regions that are rich in the voltage-gated K+ and Na+ channels that are fairly excitable
Saltatory Conduction
Jumping from node to node. It accelerates the nerve transmission in myelinated neurons.
*Since the myelinated neurons in mammalian cells are fairly thin, the conduction velocities increase by this adaptation because now we’re not expecting that every micron of axon is covered with the voltage-gated channels to propagate an action potential.
Conduction velocity in mammals
70-120 m/sec
Forebrain
Has activities that include processing of olfactory input (smells), regulation of sleep, learning, and any complex processing, including learning and other complex processes/decision-making
Contains the cerebrum
Midbrain
Coordinates routing of sensory input that is coming into brain
Hindbrain
Controls involuntary activities such as blood circulation, & coordinates motor activities, such as locomotion (also respiration rate)
Variations in the regional specialization of the vertebrate brain
- In ray-finned fish that are free swimming, there’s a demand for control of movement in open water which is why the hindbrain is larger
- In birds and mammals that process higher levels of learning, memory, and decision making, the largest portion of the brain is the forebrain (cerebrum)
Central Nervous System
Brain and Spinal Cord
Peripheral Nervous System
All the nerves that emerge from the brain, cranial nerves, and spinal cord/nerves
Includes ganglia, neuronal cell bodies that are present outside the brain & spinal cord
How do messages move around the system ?
Internal & external stimuli –> Sensory receptors –> Afferent neurons –> CNS –> Efferent neurons –> (either) Autonomic nervous system or motor system
Autonomic nervous system —> (either) sympathetic or parasympathetic division
Motor system –> Control of skeletal muscles
Afferent neurons
Neurons going towards the brain and spinal cord
Efferent neurons
Nerves that are emerging from the brain and spinal cord
Autonomic nervous system
Free of voluntary control. The autonomic nervous system functions by maintaining parasympathetic & sympathetic actions and balance.
Sympathetic
Associated with fight or flight, severe state of excitation
Parasympathetic
Rest and digest phase
Increase in parasympathetic activity will…
Decrease sympathetic activity & vice versa so that there is a dynamic balance between the two autonomic branches
Sympathetic division as the neuronal outflow from…
The thoracic and lumbar region
Parasympathetic division as the neuronal outflow fro
The cranial and sacral region of the nervous system
The Sympathetic Division
Wants to prepare the animal to be highly sensitive due to flight or fight. Therefore:
- Dilates pupil to allow more light
- Inhibits salivary gland secretion
- Relaxes bronchi in lungs and allows for higher oxygenation levels
- Accelerates heart so circulation improves
- Inhibits activity of stomach and intestines
- Inhibits activity of the pancreas
- Stimulates glucose release from liver; inhibits gallbladder for higher level of activity
- Inhibits emptying of bladder
Promotes ejaculation and vaginal constriction
The Parasympathetic Division
- Constricts pupil of eye for less light
- Induces salivary gland secretion
- Constricts bronchi in lungs
- Slows heart
- Stimulates activity of stomach & intestines
- Stimulates activity of pancreas
- Stimulates gallbladder
- Promotes emptying of bladder
- Promotes erection of genitalia
Loewl’s Experiment
An experiment where they shocked vagus nerve of a frog heart with a stimuli which stopped the heartbeat. When they took the liquid secreted (acetylcholine) and put it in another heart, it also stopped
–> Shows that acetylcholine inhibits cardiac rate
Synapse
A connection or communication between a neuron & another neuron or a neuron and another cell type
Chemical synapse
Consist of a presynaptic cell, which is the neuron, and the postsynaptic cell, which is the target neuron or the cell type
There is a small space between the two called the synaptic cleft
How does a chemical synapse work?
- Presynaptic cell has vesicles inside which contain the chemical which is the neurotransmitter
- The presynaptic terminal has voltage-gated calcium channels that allow for Ca2+ flow into the cell
- When this cell is stimulated, there is fusion of these vesicles to the membrane of the presynaptic cell, releasing the chemical to the synaptic cleft
- In the synaptic cleft, these neurotransmitters can bind to ionotropic or metabotropic receptors
- The chemical acts on the postsynaptic cell to bring a response in the postsynaptic cell. It leads to gene expression, biochemical cascades, and membrane potential which leads to responses in the postsynaptic cell.
Importance of Ca2+ in cell
Calcium influx triggers the synaptic vesicle to fuse and release their neurotransmitters into the synaptic cleft
In the synaptic cleft, these neurotransmitters can bind to ionotropic & metabotropic receptors.
Electrical synapse
In electrical synapses, two cells are connected by gap junctions
Gap junctions
Two transmembrane complexes that are sitting aligned in such a way that they form a channel in between them
There are two hexameric connexin hemichannels that have a conduit for passage of ions and small molecules that can happen in both directions
This means that any action potential traveling down the axon with an influx of Na+ can directly be transmitted to the next cell and cause a potential in the postsynaptic
Why are gap junctions a typical feature of escape response networks in both vertebrates and invertebrates?
- Reliable
2. Instantaneous, no synaptic delay
Drawback to electrical synapses
Does not have the level of amplification of signal for it to propagate over multiple interneurons (like chemical signals do)
Inhibitory postsynaptic potential (IPSP)
Cause hyperpolarization through the release of K+
- Acetylcholine acts on the muscarinic cholinergic receptor and triggers G-proteins that result in the opening of the K+ channel
- This opening of K+ channels results in hyperpolarization of this particular plasma membrane because K+ is being sent out of the cell and this hyperpolarization would prevent the triggering of an action potential
Excitatory postsynaptic potential
Causes depolarization through the release of Na+
- Norepinephrine binds to Beta-1 adrenergic receptor which triggers G-protein-coupled action. In activating Adenylate cyclase, which converts ATP to cyclic AMP, which is a second messenger, it activates protein kinases which in turn phosphorylates specific channels like the Funny channel (Na+) and the T-type calcium channel that allows for Ca2+ influx
- Causes depolarization which triggers the action potential
Parasympathetic makes the postsynaptic neuron…
LESS likely to fire an action potential
Sympathetic makes the postsynaptic neuron…
MORE likely to fire an action potential
Metabotropic Receptors
Require a second messenger to trigger the opening of a channel
Use GCPRs
Ionotropic Receptors
Require the molecule alone to trigger the opening of a channel
Transmembrane ion channels
Antagonist
A substance that blocks the particular action (ex. atropine suppresses the parasympathetic event to increase the sympathetic and dilate the eyes)
Agonist
Promotes the particular action (ex. muscarine increases the parasympathetic)
Acetylcholine
Inhibitory: Binds to muscarinic acetylcholine receptor (GPCR) coupled with K+ channel that causes hyperpolarization
Excitatory: Binds to nicotinic acetylcholine receptor (ligand-gated Na+ channel)
How to remove the neurotransmitter after you have activated the post-synaptic cleft?
1) Enzymatic breakdown where inactivating enzymes in the postsynaptic neuron would break down the neurotransmitter (ex. acetylcholine esterase)
2) Reuptake of the neurotransmitter that is released. There are neurotransmitter transport channels to take neurotransmitters back into the presynaptic cell. (ex. norepinephrine transporters)
Effects of Novichok drug (you can probably skip this one)
- Acetylcholine that is not removed from the synaptic cleft results in persistent stimulation of both muscarinic and nicotinic acetylcholine receptor stimulation
- Inactivating enzyme breaks down acetylcholine but it sticks around in the synaptic cleft and continues to activate the receptor
- Persistent postsynaptic activity and the acetylcholine released will slow down the heart and lead to death
Norepinephrine
Inhibitory: Binds to alpha 2 adrenergic receptor (GPCR)
Excitatory: Binds to alpha 1, beta 1, beta 2, beta 3 adrenergic receptors (GPCRs)
Inhibitory neurotransmitters:
GABA and Glycine
GABA (draw)
Binds GABA receptors (ligand-gated chloride channel)
Glycine
Binds glycine receptors (ligand-gated chloride channel)
Why do GABA and Glycine release chloride to inhibit?
Cl- neutralizes Na+ and stops action potentials
Subthreshold, no summation (draw graph)
Stimulation is not sufficient to take the axon hillock to the threshold so the excitation terminates in the axon hillock
Temporal summation (draw graph)
If there is a summation that means the stimuli are close enough that the Na+ influx that happens in the first peak can be supplemented with the second excitation which takes it to a new peak
Spatial summation (draw graph)
Excitatory signal coming from E1 and E2 at the same time that results in a much more robust Na+ influx and reaches threshold faster
Spatial summation of EPSP and IPSP
Inhibitory neurotransmission (GABA and glycine) can result in hyperpolarization rather than depolarization
Glutamate
Binds NMDAR, AMPAR, Kainate R, mGluR (don’t need to memorize this)
Excitatory: Learning and memory
When glutamate is released into the synaptic cleft, it is by reuptake, going into the presynaptic cell; however, this reuptake involves another cell which is non-neuronal, glial cell, which first transports glutamate and then allows the presynaptic cell to take it
Neuronal plasticity at resting (draw)
The baseline impulses are traveling through a glutaminergic presynaptic terminal and glutamine is released and binds to the AMPA receptor
Sodium enters cell so it is depolarized. However, the NMDA receptor is blocked by Mg so that there is no opening of the NMDA receptor that binds to glutamate
Neuronal plasticity during postsynaptic depolarization (draw)
If the frequency of stimulation is high and there is persistent depolarization because of this synapse being extremely active, we have a voltage dependent exit of Mg from the channel and allows for rapid Ca2+ influx into the postsynaptic cell
Long-term potentiation
Ca2+ acts as a second messenger which leads to the long-term potentiation. The entry of Ca2+ activates second messengers like kinases or other signaling molecules which trigger phosphorylation events which activate specific pathways. Allows for vesicles with more AMPA receptors to be placed on this postsynaptic membrane –> Na+ influx strengthened
–> circuits are responsible for learning and memory
Dopamine
Binds dopamine receptors like (GCPR)
Anticipation of a reward (organism wants more)
Circuit for Dopamine
The LH6 Glu nucleus providing the glutaminergic nervous supply to the nucleus that would influence the GABA neuron
Glutamine release would excite the GABA neuron which will inhibit the dopaminergic neuron
HOWEVER
If the glutaminergic neuron does not get excited, the GABA neuron doesn’t get excited to release gaba and inhibit dopaminergic neuron
*Opiates (opioids) and cannabinoids also have receptors which are GPC IPSPs and can block the GABA release to increase dopamine release
Serotonin
Binds 7 different types of serotonin receptors - HT3 is a ligand-gated sodium and potassium channel (excitatory), the remaining 6 are GPCR
Known to regulate anxiety, cognition, mood, learning, thermoregulation
Selective Serotonin Reuptake Inhibition (SSRIs)
That potentiate serotonin-based effects are effective treatment for some types of depression
Sensory Processing
- Reception: receipt of a signal by sensory receptors
- Transduction: Conversion of a sensory stimulus into electrical energy in the nervous system by a change in the membrane potential
- Perception: Individual interpretation of a sensation; a brain function (is it a taste or hearing stimulus? What is the quality)
Two ways for sensory reception
- Neuronal cell: The stimulus can directly be picked up by a neuron which is acting as the receptor receptor is afferent neuron)
- Non-neuronal receptors: Specialized sensory receptor cells that respond to the stimulus by releasing some neurotransmitter that activates a neighboring neuron that takes the signal to the central nervous system
Mechano-sensing Channels
Direct:
If the membrane receptors are ion channels, there could be forces that are acting at the level of the membrane that pull them apart and allow the membrane to become permeable to ions. This depolarizes the cell
Indirect:
There could me anchors that are tethered to the extracellular matrix or the interstellar cytoskeletal elements that might pull and drag in different directions when there are mechanical forces. This opens the channel and allows ion flow.
Mechano-sensing transducers
There could be secondary transduction of the mechanosensing signals where the compartment that senses the channel is completely different from the channel itself if a way that the mechanical forces are encountered by a signaling complex which results in signaling intermediates and second messengers that then allow the binding to the mechano-sensing channel –> ion flow and depolarization
Glabrous skin
Part of skin without hair (ex. palm)
The Glabrous skin contains
- Specialized receptors called Ruffini endings. They are responsible for recognizing stretch along the skin surface
- Pacinian corpuscles allow for deep pressure detection and also vibrations
- Merkel cells sensitive to touch, pressure, indentations
- Meissner corpuscle detect vibration and some level of pressure
Hairy skin contains
3 types of hair: Guard (thicker), Zigzag, Awl
- Lanceolate endings which detect hair follicle deflection (any movement of the hair follicle or the hair circuit moving from one direction to another)
- Free nerve endings are actually HTMR which means they are high threshold mechanoreceptors so they are not activated by mild stimuli and they detect pain. They recognized noxious stimuli and respond by detecting pain
- Guard hairs contain Merkel cells
HTMR
High threshold mechanoreceptors so they are not activated by mild stimuli
LTMR
Low threshold mechanoreceptors so they are activated by mild stimuli
Sensory stimulation of hairy skin: Poke
If there is a poke on the skin surface, the Merkel cells are mostly activates because they’re very sensitive to any changes in pressure. However, if the hair is not involved, then the lanceolate endings aren’t really triggered
Sensory stimulation of hair: Stroke
The stimulus will tap on the hairs and that is going to fire up the lanceolate endings. There’ll be some activation of the Merkel cells
Sensory stimulation of hair: Breeze
Since there is no touch on the surface, the hair will be blown. The level of deflection depends on the size of the hair (guard hairs will be less deflected) so the lanceolated endings for the awl hair will be triggered. No activation of Merkel cells.
Two types of responses seen in receptors
Slowly adapting receptors
Rapidly adapting receptor
Slowly adapting receptor
(Tonic) When the stimulus is perceived, there is a higher frequency of action potential firing but if the stimulus persist over a period of time, this frequency plateau into a low rate of firing as long as the stimulus is present
Rapidly adapting action receptors
(Phasic) There’s a high rate of action potential being fired when the stimulus is turned on; however, when the stimulus is persisting, we have no action potentials being fired. When the stimulus turns off, there’s indication (single frequency) to show that the stimulus is off
Importance of slowly and rapidly adapting action receptors
Rapidly adapting receptors are known to provide information for rapidly moving stimuli (ex. rubbing finger across the skin)
Slowly adapting receptors are know to provide more info about the spatial and size of the stimulus
Which skin receptors are Tonic (slow adapting) and Phasic (rapidly adapting)?
Tonic: Merkel discs (cells), Ruffini endings
Phasic: Meissner corpuscle, Pacinian corpuscle (extremely phasic)
Since coding can be ambiguous, there isn’t a linear line for action potential frequency. So as you increase the indentation velocity…
(strength of a stimulus) the action potential is not linear, it’s sigmoidal
Threshold
The minimum intensity of a stimulus that is required to produce a response from a sensory system (the absolute threshold is the point where only half the number or receptors are able to fire action potentials for that particular stimulus)
Log-linear
This phase follows the threshold where there is a log-linear increase with the increase in the stimulus intensity
Saturation
The maximum intensity of a stimulus that produces a response from a sensory system
Dynamic range
The range of intensities that will produce a response from a receptor or sensory system (i.e. the difference between the threshold and saturation
Within a certain modality (ex. group of Meissner cells), individual receptors will have different threshold and dynamic ranges.
Different mechanoreceptors vary…
In size and structure of their receptive fields (RFs)
Receptive field
A sensory reception associated with a single sensory neuron (so if a stimulus is present in a certain space, the neuron will fire)
Each sensory neuron is associated with a specific receptor field for each type of receptor
There are both __ and ___ receptors in the palm of our hand
Superficial and deep
There are some regions that will have a ___ response even with the same intensity of stimulation (Hand)
Lower
* Same ideology for the deep receptors where the periphery is weaker and towards the center there is more of a response
Spatial discrimination
For spatial discrimination, there needs to be a receptive field in the middle that is not contacted or minimally contacted by the 2 points of stimulation
The size of your receptive field determines…
how sensitive you are in different places of your body
ex. in your fingers, the spatial discrimination may only need to be 4 mm or less spart
ex. in your back and belly, the spatial discrimination may need to be 30 mm apart
