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
When the density of receptive fields is much higher…
It is possible to get unstimulated receptive fields in the middle much more easily when compared to densities that aren’t great (back) and the size of the receptor is also different
Primary somatosensory cortex
Processing occurs in the somatosensory cortex and the decision of what needs to be done as a result of that is then transmitted to the primary motor cortex.
Leg, Hip, Trunk, Neck, Head, Upper arm, Elbow, Forearm, Hand, Fingers, Thumb, Eye, Nose, Face, Lips, Teeth, Gums, Jaw, Tongue, Pharynx, Abdominal organs, Genitalia
Primary motor cortex
Can send a message from the brain to the target organ (very likely a muscle) to induce a particular movement
Toes, knee, hip, trunk, shoulder, elbow, forearm, wrist, hand, finger, thumb, neck, jaw, lips, tongue, eye, brow, face
How is a sensory signal sent through the primary somatosensory and motor cortex?
Sensory signals arriving at the somatosensory cortex are processed to make a decision and are sent to the motor cortex to induce an action after the processing has been done
Touch circuits in the CNS pt1
- Receptors in the fingertips affect the mechanosensory afferent fibers and pain and temperature afferent fiber
- Then the neuron cell bodies in the dorsal root ganglion cells have the neuron (or information) enter the spinal cord
- As it moves into the medulla, it gets sharpened by an interneuron, the location is called the Gracile Nucleus or the Cuneate Nucleus
- Then the flow of information is relayed through a region called the thalamus before it actually leads to the somatosensory cortex
First order of transmission
The receptor ending (in fingertips) to the nuclei (gracile and cuneate nucleus)
Second order of transmission
From the nuclei to the thalamus
Third order of transmission
From the thalamus to the somatosensory cortex
Touch circuits in the CNS pt2
- Individual signals are in discrete tracts (means that signals could be in the same nerve but they are different axons that are taking individual information from each receptive field)
- Flow to the opposite side of the brain
- Almost all information relays in the thalamus
- Each signal can differ in conduction velocity (so the types of neurons can be different in the thickness of the myelin and also the thickness of the axon, therefore affecting the speed)
- Differ in activity (due to what kind of mechanosensation it is and also the other type of sensory systems are going to send action potentials to different regions of the brain
Lateral Inhibition
Can sharpen spatial decoding
When there is a high frequency of action potential coming from a neuron, it stimulates a inhibitory neuron like GABA that connects to the signal arriving from the adjacent neurons.
This inhibition can eliminate or minimize what is transmitted because of the singular high frequency
Overall, the frequency of the stimulated neuron (with a lot of action potentials) activates the inhibitory neuron which drives the chloride out of the presynaptic area, therefore, the Na+ current flowing in will neutralize the action potential. Therefore, little to no stimulus travels to the 2nd order neuron except for the signal going through the main neuron. After the 3rd order transmission, the brain will only see the area of the high frequency action potential and won’t recognize the adjacent neurons.
Conduction velocity of sensory fibers differ due to…
Change in axon diameter
Extent of myelination
Creates different rates of action potential flow or the speed of transmission of axons
Another organ that uses mechanosensing is ___ because _________________
Hearing because vibrations are picked up by mechanosensors and are interpreted as sounds
Invertebrate hearing
In invertebrates, there’s a region in the forelimb that has a membrane that can pick up these vibrations and sensory elements associated with the membrane to transmit the signals to the nervous system
Hearing: the mammalian cochlea
- Sound waves travel through the auditory canal and vibrate the tympanic membrane to provide mechanical stimuli
- The vibrations are carried through 3 small bones called the auditory ossicles (mallues, incus, stapes)
- These vibrations are transferred to the inner ear and the cochlea which has the mechanoreceptors necessary for producing or detecting the sound vibrations
- The vibrations from the stapes is transferred into the fluid compartment of the cochlea (perilymph)
- Waves travel towards the top, then back. In that process, they vibrate the basilar membrane
- The basilar membrane is what contains the mechanoreceptors for sound
- The particular mechanosensing setup is called the organ or corti
Organ of Corti
Sound waves beating on eardrum vibrate the basilar membrane which bends hairs
- There is one row of inner hair cells and there are 3 rows of outer hair cells
- Sitting on top is the tectorial membrane in the endolymph region
- When the basilar membrane vibrates, we have the hair cells being bent in one direction or the other
- The bending of the hair cells trigger action potentials that reflect the degree of the vibrations
Inner hair cells
Sensory in the sense that when the hair bends, there are some graded potentials established that fire action potentials that travel to the auditory nerve and CNS
Outer hair cells
Motor signals in that they are able to contract or relax or control the vibrations of the tectorial membrane
It’s likely that the outer hair cells help to sharpen the frequency resolving power of the cochlea by actively doing this contraction and relaxation
Endolymph is high in __
K+
The endolymph compartment is high in K+ due to a group of specialized cells called marginal cells which secrete K+ into the endolymph. Therefore, K+ entering results in depolarization
Mechanotransduction by the hair cells
Mechanosensation by the hair cell occurs by the direct opening of K+ channels.
- If the hair is deflected to one side (like the left for instance), there is hyperpolarization
- If the hairs are moved to the opposite side )like the right), they are depolarized and the channels are pulled open by protein elements
- The channels are tethered by small protein elements so that when the hair moves, the channels could open or close
- This depolarization results in Ca2+ influx, fusion of the vesicles that include neurotransmitters (glutamate) into the synaptic cleft, activating an afferent nerve that signals to the auditory nerve in the brain
Receptor potential magnitude encodes stimulus magnitude and transmits by regulating action potential frequency
As the sound gets louder & quieter, by the deflection of the hair cells either depolarization or repolarization (everytime it depolarizes it releases glutamate) which increases the number of spokes that is transmitted through the auditory nerve
Smell is a ___ sense.
Chemical sense.
Odorants
Chemicals that are detected by the olfactory system to attribute particular smells
Smell in mammals
- Within the nasal cavity, there’s a specialized region that contains olfactory neurons that can detect the sense of smell
- In the olfactory epithelium, there are olfactory receptor cells, which are neurons that fire their own action potentials
- They have these protrusions (cilia) within the mucus layer and contain receptors that would detect various odorants that are coming into the nasal passage
- Once an odorant binds to its receptor on the cilia of a neuron, it fires an action potential that reaches the olfactory bulb of the brain where it interprets the smell
Important olfactory receptor characteristics
- Olfactory receptor cells are neurons (not epithelial cells)
- Receptors are GPCRs
- Each cell has only one receptor type - this is how the brain can tell what smell its sensing. Each olfactory receptor cell has only a specific type of receptor in the cilia that can respond
How does the olfactory receptor GPCR work?
- Odorant attaches to the GPCR which activates the G Protein to Adenylate cyclase
- Adenylate cyclase uses ATP to make cAMP which binds to a cAMP gated ion channel which ends up in Na+ or Ca2+ influx
- Causes depolarization of a cell and the ability to transmit an action potential
Combinatorial population coding
Uses information from different neurons, quantity of activation, diversity of activated neurons, and property of the chemical itself to activate different neurons in combination to create an array of olfactory senses that can be detected by humans
1. A single olfactory receptor can respond to several different compounds. They transmit action potentials that are frequency coded based on odorant.
2. One compound can stimulate multiple olfactory receptors
3. Smell is interpreted by the combined measures of stimulated olfactory receptor types and their action potential frequencies
This creates a combination which is then decoded by the brain
Tongue
The organ that detects taste which has a distribution of different papillae
Papillae
Epithelial eruptions that have taste buds
These papillae contain a variety of taste receptors, modified epithelial cells, and they signal to nerve endings when they encounter a particular chemical or tastant
5 major taste that can be detected by receptors in taste buds
Sweet Sour Salty Umami Bitter
Taste receptors
Each cell has only one receptor type - so certain cells can only detect a certain type of taste so that they could create graded potentials that will signal to a particular sensory neuron which code the information using the frequency of the action potential
Sweet, Umami, Bitter (draw diagram)
Recognized by GPCR
- Tastant binds to GPCR which activates IP3 which binds to its receptor that is in the ER which is a Ca2+ store. When it binds it releases Ca2+
- This Ca2+ activates the TRPm5 channel which is a Na+ channel that would result in an influx of Na+, depolarizing the cell
- This depolarization signal results in presynaptic transmission by fusion of the vesicles containing neurotransmitters to a neuron that would fire an action potential (epithelial cell signaling to a neuron to fire an action potential)
- The graded potentials that can occur in this epithelial cell would result in changes to frequency of action potential firing of the neuron (reflects on the intensity of the tastant )
Salty (draw diagram)
Channels involved is a Na+ channel (ENac)
- The external concentration of Na+ allows for Na+ influx
- Na+ influx would result in the depolarization of the cell
- Graded potentials and release of neurotransmitters at the presynaptic junction cause action potentials being fired by neurons.
Sour (draw diagram)
A proton channel
- There’s a proton channel called OTOP1 which transports protons and results in depolarization.
- Creates graded potentials and that would have neurotransmitter release and action potential frequency depending on the degree of depolarization
Neurotransmitters released
Acetylcholine
Serotonin
Norepinephrine
All involved in transmitting the greater depolarization event to the neurons that travel to the sensory parts of the brain where taste is interpreted
What was discovered through the PBDG experiment?
It is not the tastant that codes for bitter and sweetness. but it’s actually the cell
The brain doesn’t know what the trigger is, but it only knows that a particular cell is being activates and codes for what that cell is normally responsible of.
Vision
The ability to detect photons or light
Planarian
An organism with eye spots, cup-shaped depressions that contained photoreceptors (ocellus)
- The depression has some sort of pigment that can reflect or enhance the light its seeing
- It also has photoreceptor cells that contain the ability to detect whether there’s light or dark and are able to transmit to the brain through these particular axons
Vision in Invertebrates
Insects can detect light and color
- They have numerous kinds of independent units called a ommatidium that are spread across this convex structure which forms the eye (think abt flies)
- The ommatidium has its own sensory neurons that are traveling to the brain and they task the photoreception system
- Photoreception results in signaling to the sensory system
- It has a crystalline cone which acts as a lens and has a corneea so that it is able to detect light and take it down
Benefits of insect compound eye
- Convex arrangement is good for light direction
- Very sensitive to movement
- Color vision (has different photoreceptor cells)
- Bees can see into the ultraviolet range of light (not detectable by the human eye)
- Mantis shrimp have 12 different color photoreceptors
Vision in vertebrates: Single lengs eye
- Light flows through the cornea, through the pupil, through the lens, into the vitreous humor until it hits the retina
- If you were to zoom into an area of the retina, there would be optic nerves followed by a layer of interneurons and then photoreceptors in the forms of rods and cones
- Light hits the pigmented retina and the reflected light is gathered by photoreceptor cells which communicate to the sensory neurons to take the signal back to the brain for interpretation.
- Interneuron layer ues lateral inhibition to make sure that you are seeing a specific color such as seeing red instead of a blend of red
Rods
Responsible for greyscale
Humans have 1 greyscale photoreceptor
Cones
Responsible for color
Humans have 3 color photoreceptors
Where does the photoreception take place?
The photoreceptor cell has a region called the membrane disc where the signalling actually takes place
Photon-mediated activation of GPCR
- GPCR is seen together with a molecule that can be activated by photons
ex. Inactive Rhodopsin –> Photon –> Active Rhodopsin
When the active rhodopsin is formed because of the photon in complex with the GPCR, then signaling is possible
Photoreception in the dark
- The rhodopsin molecules are actually arranged on the disk membrane. In an inactive state, rhodopsin does not signal and it is with another protein called transducin
- Transducin is capable of activating phosphodiesterase to break down cyclic GMP
- Therefore, in an inactive state, the phosphodiesterase is inactive so cGMP is high in the cytoplasm. It can bind to the cGMP gated Na+ channels and allows Na+ to influx into the cell in the dark
- Without light, cell is depolarized which releases neurotransmitters (glutamate) at the presynaptic terminal –> action potential can trigger in the interneuron layer to hyperpolarize the bipolar and ganglion cell.
- This means no action potentials are going to the brain through the optic nerve
Photoreception in light
- When there is light, rhodopsin is activated which activates transducin and results in activation of the phosphodiesterase which converts cGMP to GMP and depletes the cGMP
- Therefore, there is no more cGMP available to keep the cGMP gated Na+ channel open
- Cell becomes hyperpolarized, seizes to release glutamate, and action potentials fired in the postsynaptic cells are stopped
- Bipolar and ganglion cells are depolarized due to lack of glutamate
- Action potentials are going to the brain through the optic nerve
Different spectral sensitivity of photoreceptors is due to…
Different opsins
3 color receptors: S cone, M cone, L cone
1 grayscale rod
By having the rods and cones so close to one another….
They can work together to create a combination of colors
Lateral inhibition in the eyes (diagram)
Through lateral inhibition, the boundaries of specific colors are enhanced
- If the center is exposed to light and the surrounding is not, then we have less glutamate being released by the center. This triggers the bipolar cells to take the signal to the brain.
- The surround cells (in the dark) have higher levels of glutamate and trigger the horizontal cells that provide this negative feedback to the synaptic junction. This decreases the glutamate release in the presence of light much less
3 Types of Skeleton
Internal/Endoskeleton: Flexible joints held together by proteinaceous ligaments. Antagonistic muscles spans the joint and attach to stiff plates or bones (ex. humans)
External/Exoskeleton: Cuticle is generally hard, but has a flexible membrane at joints. Antagonistic muscles span joints and attach to stiff cuticle. (ex. insects, arthropods, mollusks, brachiopods)
Hydrostatic: Body cavity is kept under pressure by a muscle wall (antagonistic circular and longitudinal muscles) (ex. worms, insect larvae, some mollusks)
Skeletal muscle
A voluntary muscle which means it’s under conscious movement (contraction or relaxation)
A skeletal muscle consist of
- Bundle of muscle fibers
- Inside each bundle are single muscle fibers or muscle cells (multinucleated)
- In each muscle cell are myofibrils
Are skeletal muscle cells multinucleated?
Skeletal muscle cells are multinucleated. Due to the contractile elements (myofibrils) occupying the cytoplasm, the nuclei of the muscle cell are pushed to the edges.
Sarcomere (draw)
The structure behind the striations. The myofibril is composed of a repeating unit called the sarcomere.
- Myosin (thick filaments) are the region of the A band
- Actin (thin filaments) are the region of the I-band but can overlap in some regions of the A-band
- Z-line separates individual sarcomere units
- During contraction, the sarcomere reduces to 70% of their normal size
Sarco refers to
Flesh
Other structures in the skeletal muscle cell use phrases like sarcolemma (plasma membrane) and sarcoplasmic reticulum (endoplasmic reticulum)
Mitochondria in the skeletal muscle cell
There are many mitochondria distributed throughout the length of the fiber receiving O2 released from hemoglobin in the blood, and muscle myoglobin
T-tubules of the sarcolemma
The sarcoplasmic reticulum is covering each myofibril
The plasmalemma is continuous with the set of T-tubules
- The function is that when there is an action potential that is spreading on the plasma membrane of the cell, the T-tubules can take that same action potential into the depths of the cell (this is an important function because the sarcoplasmic reticulum functions as the Ca2+ store)
- The action potential traveling down the T-tubule encounters what is called the dihydropyridine receptors and there receptors can transduce the action potential signal to the opening of the Ca2+ channels –> allowing Ca2+ to exit from the sarcoplasmic reticulum
*Important first step in contraction
Z-line
- The point of separation between one sarcomere and another
- Also forms the point of anchor for the thin filaments, actin, and also the thick filament, myosin
What stabilizes the thin filament?
Nebulin. Does this so actin does not unwind
What stabilizes the thick filament?
Titin
The polarity of actin and myosin…
Reverse at the M line (two halves contract or pull in the opposite direction)
Myosin
Acts as the motor to move or walk across the binding sites
The Power Stroke for an individual myosin head (draw out if needed)
- In the low energy configuration, the myosin head group is angled backward until it binds with ATP
- When ATP binds to the myosin head group, it moves to a high energy configuration, which is the more perpendicular angle of the head group. During this process, the ATP is hydrolyzed to ADP and P but it is still anchored to the binding site in the head group
- With high energy configuration, the head group can actually cross-bridge to and bind to the actin filament
- When this is successful, the ADP and P depart from the myosin head group
- Once it departs, the myosin is forced to head back to the low energy configuration
- The angular positioning returns and the thin filament moves towards the center of the sarcomere
* With each stroke, we have a small movement to the center of the sarcomere of the actin filament. This allows the myosin to slide to the right and actin to slide in the reverse direction so that the sarcomere contracts
Troponin
Made up of 3 proteins, one of which binds Ca2+
Tropomyosin
Binds actin end-to-end as a polymer
Troponin-tropomyosin complex
- In the resting state, the troponin-tropomyosin complex hides the myosin binding sites
- Once Ca2+ molecules are released by the sarcoplasmic reticulum, it binds to troponin, shifting the whole protein so that the myosin binding sites on the actin filament are exposed
- Now, myosin can bind to actin and complete its power stroke
Steps in skeletal muscle contraction
- Acetylcholine is released from synaptic cleft
- Action potential travels on its surface of the cell and dives into the T-tubule network
- Activates the dihydropyridine receptors on the sarcoplasmic reticulum –> Ca2+
- This Ca2+ from the SR binds to the troponin which exposes the myosin binding sites on the actin filament
- Myosin binds, burns ATP, and slides across the actin which results in contraction
How do you reverse contraction?
Ca2+ must be pumped back into the sarcoplasmic reticulum, reducing the free Ca2+, and hiding the myosin binding sites on the actin filament
Ca2+ pump requires energy, however, relaxation will passively allow the actin to slide back.
Skeletal muscle relaxation
- Acetylcholine removed by acetylcholine esterase
- No action potential being sent down the T-tubule
- Ca2+ reuptake
- No Ca2+ can bind to troponin exposing the binding sites
- Contraction ends and actin slides back into place
Does contraction or relaxation use energy?
Both
Contraction uses energy for the Myosin head group
Relaxation uses energy for the reuptake of calcium through active transport
Each individual cell in a muscle is innervated by…
One, and only one, motor neuron
Twitch
A muscle twitch or contraction event, results from one action potential arriving from a single motor neuron
Motor unit
The number of cells that particular motor neurons innervate is called the motor unit
If you have the arrival of two action potentials,
they can combine te twitches and strengthen the contraction (temporal summation)
Recruitment of motor units
- Every muscle can have multiple motor units and the CNS determines the number of motor units that are triggered to contract the muscle
CNS affect on contraction strength
- The CNS can choose to activate more motor units that will result in a higher strength of contraction. Once all the muscle cells are activated, then we have the maximal contraction
Electric organ
A modified muscle cell that allows species to transmit small pulses of currents to determine what is getting reflected. This allows it to locate where things are moving.
Can also detect other organisms’ electrical currents
Importance of Cl- channels
Ca2+ needs to go back into the sarcoplasmic reticulum but this process may be too slow and cause residual contractions
- The Cl- channels prevent these residual contractions from happening because it can rapidly neutralize the environment of any positive charges and prevents Ca2+ (free) from binding with troponin
Myotonia congenita
Dysfunction in the Cl- channel where you have residual contractions that exist before the muscle is able to completely relax (ex. fainting goats)
Cardiac muscle
Only found in the heart, consists of striated cells electrically connected by gap junctions called “intercalated disks”
- The action potentials in cardiac muscle cells are rapidly transmitted from cell to cell because of the presence of gap junctions
- Electrical synapses exists between the cardiac muscle itself (do not have T-tubules) which allows for cell-cell contact and ion flow allowing for depolarization signals and calcium to flow through these particular gap junctions
Contraction of the heart
- A single cardiomyocyte being activated can result in the whole heart contracting and there are junctions and desmosomes. The actin-myosin complex exists in the heart.
Smooth muscle
Found in tissues that have. alumen such as the urinary bladder, blood vessels, lung airways, or the digestive tract.
The wall of tubular structures contain smooth muscles which aren’t multinucleated cells like the skeletal muscle, but they’re just spindle-shaped cells that can contract individually and bring about smaller size of the cell itself
Peristalsis
The idea that we move the material inside the lumen towards the region that would either eliminate or move it to the next compartment.
The tubular organs have 2 layers of the muscle
Inner circular muscle
Outer longitudinal muscle
Inner circular muscle
Contraction of the circular muscle causes tightening behind the food mass. This is the orientation of how the muscle is going to contract
Outer longitudinal muscle
Contraction of longitudinal muscle moves the food mass ahead
How does food move down a smooth muscle system?
- Contraction of inner circular muscles behind food mass
- Contraction of longitudinal muscles brings about sharpening of the entire tubular organ itself
- Contraction of the inner circular muscle in certain undulations pushing the bolus of food in one direction
Smooth muscle structure
No myofibrils but they have actin and myosin (not organized in sarcomere)
No troponin-tropomyosin complex but the Ca2+ is mediated by a regulatory protein called calmodulin
Dense bodies
Similar to the Z-discs but are anchored to the sarcolemma. Actin and myosin are attached to dense bodies.
Where is calcium released from in smooth muscle?
The L-type Ca2+ channel and sarcoplasmic reticulum
Smooth muscle contraction
- Dense bodies which have tethered actin and myosin can pull on the plasma membrane to effect a smaller size of the cell
- When myosin walks on actin, the dense bodies are pulled, which then pulls on the plasma membrane –> contracted cell
Ca2+ in smooth muscle contraction (draw)
- When Ca2+ arrives in the cytoplasm, its main function is to bind to calmodulin and Ca2+ bound calmodulin activates myosin light chain kinase (from inactive to active using ATP) and this kinase is able to phosphorylate the myosin head group
Smooth muscle relaxation
Brought about by the:
- Removal of Ca2+ from the cytoplasm (uses ATP) removing the chance for Ca2+ to bind to calmodulin
- Therefore, the myosin light chain kinase is not going to activate anymore
- The activated phosphorylated forms of myosin that are already present have to be dephosphorylated by a myosin phosphatase making them inactive and unable to bind to actin
Are smooth muscles voluntary?
No, smooth muscles contraction aren’t in our control. Unlike the skeletal muscles, a stimulus can relax or contract them
ex. asthma pumps leads to dilation which is relaxation
Proprioception
Perception of body position
Effect of gravitational force
Spindle organ of muscles
The external forces on the muscle are reported by the muscle spindle organ which is a sensory system that lives within the muscle
What does the spindle organ do?
- Signals change to muscle length (stretch)
- Signals rate of change of length (speed of stretch)
Draw a diagram of the muscle spindle organ
Slide 6 Sensory-Motor Intergration
Which motor innervates the extrafusal fibers?
Alpha motor neuron
Which motor innervates the intrafusal fibers?
Gamma motor neuron
When the alpha motor neuron contracts the extrafusal muscle fibers…
The gamma neuron innervates the intrafusal muscle fibers.
They contract in unison
Afferent axons (Primary Ia and Secondary II)
Provide sensory input about the contraction of this particular muscle and innervate the muscle spindle organ
Primary sensory ending 1a innervates towards the cener of the intrafusal fibers
Secondary sensory ending II innervates towards the peripheral of the intrafusal fibers
If there are external forces on stretch acting on a particular muscle, then…
There is an increase in discharge rate, therefore, it is a linear response
Whenever there is a stretch, the muscle spindle organ
fires an action potential and the rate of the action potential will indicate to the brain what the strength and speed of the stretch is
Primary sensory ending 1a (Dynamic phase)
- At a static phase, there is a series of action potential that is reporting no stretch
- When there is stretch, the dynamic phase (stretch), the frequency of action potential increase
- In the stretched state, it goes back into the static phase, which means that the stretch continues but does not change
- In the dynamic shortening phase, there aren’t any action potentials being fired from the spindle
- Lastly, you regain another static phase and rest at a certain frequency of action potentials
Secondary sensory ending II (Dynamic phase)
Similar pattern to the primary sensory ending 1a, but the only difference is that during the dynamic phase of the stretch, the acceleration of the action potential is not as dramatic
How does the muscle only report external forces?
The co-activation of the Alpha motor neuron (extrafusal muscle fibers) and gamma motor neuron (intrafusal fibers) prevents voluntary contraction from being reported by the spindle
Muscle condition at rest
Intrafusal and Extrafusal at rest are sending a normal rate of action potentials
Muscle condition stretched
Action potential frequency increases due to stretch
Voluntary contraction at rest
Intrafusal and Extrafusal at rest are sending a normal rate of action potentials
Voluntary contraction stretched
Action potential frequency increases because when there is coactivation, there is still sensitivity to external forces
Failure of coactivation
Let’s say there is no coatviation and only the extrafusal fibers contract, the it is insensitive and cannot report any action potentials
Golgi tendon organ
Important so the CNS knows what tension is in the muscle
Uses the 1b afferent neuron fiber
Tendon
A connection between a muscle and bone which is mainly composed of collagen fibers
How does the 1b afferent neuron pick up tension?
The afferent fibers pick up the tension due to the intercalation between the collagen fibers so when there’s a stretch pull in one direction, there’s a squeeze of these afferent fibers and that is the trigger for the action potential
Role of the Golgi Tendon Organ
Protecting the muscle from excessive tension so it isn’t damaged. If there is an excessive load on the muscle (you are carrying too much, the tension report can be used by the CNS to trigger a quick inhibitory response to the motor neuron’s signal for contraction by stopping the action potential that’s currently going down the motor neuron.
Steps for muscle relaxation and dropping a load (Golgi Tendon Organ)
1- Neuron from Golgi Tendon Organ fires (1b)
2- Motor neuron is inhibited (by the CNS)
3- Muscle relaxes
4- Drops load
Golgi tendon organ signals for:
- muscle tension
- rate of change of tension
- high threshold, vigorous is threshold exceeded
- tonic discharges similar to group 1 (primary) muscle spindle
- only responds to active muscle contractions and not passive stretches
Kinesthesia
perception of the body or its part’s movement through space
Kinesthesia in the ear
- Above the cochlea is a fluid filled structure which consists of a saccule, utricle, and semicircular canals. At the base of these canals there exist hair cells
- These hair cells have gelatinous caps called the cupula and a fluid flowing to the right at the base of the semicircular canals which can depolarize (trigger) or hyperpolarize these hair cells and the fluid low would reflect the movement of the head
Lateral line sense organ in fish
- Fish contain the lateral line sense organ which has a set of hair cells that are able to determine the velocity and directionality of the water
- Series of pores and canals that are interconnected in such a way providing inlet for the flow of water and an exit. Positioned closely to these inlets are hair cells.
Reflex
An involuntary rapid response to a stimulus mediated by the spinal cord
Patella tendon or knee jerk reflex
- Knee hammer taps the patella and the vibrations are carried all the way through the quadriceps to the muscle spindle organ because there is an external force
- Vibrations travel through the sensory 1a afferent and to the spinal cord
- It enters the dorsal horn of the spinal cord and encounters a single synapse to a motor neuron which would get back to innervating the quadriceps, releasing acetylcholine and asking for the quadriceps to contract
- At the same time, the afferent innervation also triggers inhibitory interneuron that prevents any motor stimulation of the hamstring
- As a result, the leg moves forward
Why is the reaction so fast?
The signals are sent through a single synapse and monosynaptic reflex which allows it to be fast.
Withdrawal reflex or flexion reflex
- The cutaneous receptors (stepping on needle) submit afferent information to the spinal cord
- The leg that gets stimulated is called the ipsilateral leg and the lef that isn’t is contralateral
- Cutaneous receptor transmits info into the spinal cord and communicates with a bunch of neurons in 4 pathways
1 - Inhibitory interneuron inhibiting the motor transmission to the quadriceps
2- Interneuron reinforcing mode of transmission to the flexor with acetylcholine release so that the hamstrings contract and legs withdrawn
3- Interneuron transmission leading to inhibition of the hamstring
4- Interneuron transmission leading to excitation of quadriceps
What is considered a reflex?
Rapid and involves a minimal number of neurons
Escape behavior mediated by Mauthner neurons in fish
- Sensory systems picks up stimulus and is transmitted from the ipsilateral side to the contralateral side
- The trunk muscles on the contralateral need to contract for the bending motion to occur
- Simultaneously, we have excitation of an inhibitory system which would inhibit the trunk muscle on the ipsilateral side so that the turning can occur because we want to flex in one direction
Predatory water snake exploits fish escape behavior
- The snake positions itself in a J-shaped position, allowing for the fish to investigate this particular environment
- By inducing the fish escape response, the snake predicts direction for bite and captures
Central Pattern Generator
In the CPG system, there exists what are called cellular oscillators. These are similar to SA nodes where there’s spontaneous depolarization events that are happening
Cellular oscillators
Can oscillate between rest (repolarized ) and excited (depolarization) therefore, they can alternate a stimulus between one side and the other in the form of a small circuit
- Instead of having inhibitory neurons like in reflex chains, this would allow you to repeat a pattern like swinging your legs
- We don’t have to keep conscious input for the pattern to continue. This is rhythmic behavior.
Primary and secondary components of CPGs
Primary: cellular oscillator
Secondary: Coupling with a network for repeating patterns
Cellular oscillator coupled to an on button
- This on system would continuously fire action potentials unless it is inhibited
- The oscillator is coupled to an inhibitory neuron in such a way that whenever the oscillator is excited, it sends inhibitory signals to the on system. That way, when the oscillator is firing, it inhibits the on system and when it isn’t, the on system is activated –> alternates so a pattern develops
Reciprocal inhibition coupled
- In the reciprocal inhibitor system, we have 2 cellular oscillators and they inhibit each other. When one oscillator is activated, the other is inhibited
- This is actually effective because we want to maintain the synchrony of timing over an long period of time.
Motion at the level of single cells
- Cells move using biological machines
- Cells swim and move over surfaces
- Motility is often couples with sensory systems (chemotaxis: sensing the chemicals in the environment)
Motility allows cells
- Swim towards attractants
- Avoid adverse environments
- Escape predators
- Be a predator
Motility across the tree of life
Bacteria: flagella or Type IV pili
Archaea: Archaellum
Eukarya: Cilia or flagella
Convergent Evolution
The ability of different small cells to swim using organelles that emerge from their surface and act like propellers is an example of convergent evolution
Does the cell rotate like a propeller or in beats?
Eukarya: moves in beats
Bacteria: propeller (type IV pili uses twitching mobility)
Archaea: propeller
Archaellum
- These cells have a cell membrane and the individual subunits that are going to make up this archaellum filament are synthesized and inserted into the membrane
- The protein subunits diffuse laterally into the membrane and when they encounter the base of this structure, they are assembled into the growing filament
- Once the archaellum is assembled, it can rotate using the power of ATP. There is a motor-like structure that uses ATP which is found inside the cell and causes the entire filament to rotate. Allows for swimming
- Rotation is controlled by a signaling protein called CheyY-p, that interacts with and controls the rotation of the archaellum
Type IV pilus (Twitching Motility)
- A cell body will extend from its surface a long protein filament, the type IV pilus, which then can attach to the surface and by retraction, pull the cell body across the surface
- So this involves the extension and retraction of long protein filaments powered by two different types of ATPases, one to assemble the filament and one to retract the filament
Various functions of the Type IV pili
- Adhesion: can extend from a bacterial cell surface to interact with other molecules or cells and their environment through adhesion
- DNA uptake: They can bind DNA and allow uptake of DNA into cells
- Phase binding: Can help bacterial cells attach to a surface, such as during infection
- Secrete Proteins
- Biofilms: Help bacteria bind to each other, formuning bacterial communities that are important in nature and infection
Bacterial flagella
- Assembles by the addition of protein subunits that diffuse through a hollow central pore, a channel through the filament and each new filament that’s added (each new subunit that’s added to the growing filament) assembled at the tip. This is done with the help of chaperone proteins
- The power or motor that propels the rotation of this structure is powered by the proton motive force, or in some cases, Na+ gradients
- The secretion of protein subunits to build the structure occurs at the base with a structure called a Type 3 secretion system
Type 3 Secretion System (as its own structure)
This type 3 secretion system is not for motility but to inject proteins into the host cell. The hook’s structure is now straight instead of bent and is now referred to as a needle; however, it is still a hollow structure and proteins can be bound by the type III secretion apparatus and will travel through the needle
Bacterial flagella can change with the environment
- When viscosity increases, they add more motor proteins
- When the viscosity is even higher, they create more flagella. This is known as a swarming state
Biased Random Walk
- Bacteria move towards attractants in a biased random walk
- When the motors reverse, the cells can change direction in a tumble
During a biased random walk, cells will swim for a period of time, called a run, and will randomly reorient, a. tumble, and this is interspersed with the runs
Using information from chemoreceptors, they will compared how much attractant or repellent is in the environment and tumble less if the environment is attractive but tumble more if it is worse.
Input and output of chemotaxis
Input: Protein receptors in the cell membrane. These are chemoreceptors referred to as MCPs or methyl accepting chemotaxis proteins.
- There are different receptors specific to different chemical signals (some sense amino acids, some sense sugars) and they determine whether the environment is getting worse or better
Output: Signal is sent to the switch complex at the base of the flagella. The signal protein is called CheY. CheY-P moves from the nose of the bacterium (where chemoreception occurs) to this complex of proteins at the base of the flagellum, the basal body, that can switch the direction of the motor from clockwise to counter clockwise
Signal logic of the chemotaxis pathway (how is the signal sent from the MCP to CheY-P?)
- There’s a signal sensing by the MCPs
- MCP activates CheA, a protein kinase
- CheA phosphorylates CheyY into CheyY-P
- CheY-P diffuses to the base of the flagella
- CheY-P is dephosphorylated by a dephosphorylating protein (CheZ)
Adaptation for signaling system
Good signaling systems need adaptations, otherwise, as soon as this receptor was saturated with attractant, the cell wouldn’t tell whether things were getting better or worse
- Feedback system operating through the covalent modification of these MCPs by methylation, the addition of methyl groups. There are enzymes (CheB and CheR) that add and remove methyl groups from these MCPs to change the affinity for the signal molecules
Bacterial Motility and Chemotaxis during Infection
- Bacteria can swim through a host and they can use this to find an appropriate site to grow, attach, and cause an infection
- Bacteria will also modify their flagella as a way of hiding from the immune system
- Bacteria disperse from one site of infection to another, using flagellar motility
How does the flagella hide from the immune system?
If bacteria is recognized by the immune system, it will develop antibodies that recognize that flagellin subunit as an antigen, often called the H antigen
- Bacteria can hide by changing the sequence of their flagella which is antigenic variation
- Can covalently modify their flagellar filaments (ex. the addition of glucose residues) which makes them less visible to the immune system
Difference between how the flagella and cilia move in eukarya
Flagella moves in propeller like undulations (sperm cell)
Cilia beats back and forth
The 9+2 Axoneme
- The motion of cilia and is not powered from the base, instead, it is powered from within the organelle. The organelle extends from the surface of the cell
- The plasma membrane surrounds bundles of microtubules. There is one pair in the middle and 9 around
- Using the power of ATP, these sets of microtubules slide relative to each other to allow bending
Axoneme
Bundles of microtubules connected by proteins are called an axoneme
Dyneins
The motor proteins that connect adjacent pairs of tubules
How do motile cilia move?
- Doublets of microtubules are aligned next to each other and are connected by these dynein arms
- One tubule can walk along another tubule. So when two pairs of tubules are active, they slide along next to each other
- Due to the cross-linking of tubules, as one tubule moves, as energy comes to allow movement, the movement of one set of tubules along the other causes a bending
The alternating active and inhabited filaments in a 9+2 axoneme…
cause wavelike undulations (sperm)
Primary cilia or 9+0 axoneme
Cilia aren’t used for mobility. 9 outer microtubule doublets and none in the center.
Unity of life in cilia
- The cilia that power the paramecium and in our trachea are the same cilia with a 9+2 axoneme
- Not all cilia are involved in. motility. It is found throughout the body
Ciliopathies
Skeletal functions, sensory systems, reproductive system etc. contain cilia and can be dysfunctional
*this is just to show how important cilia are
Reproduction
Production of offspring
Asexual reproduction
A parent copies itself to form genetically identical offspring
Sexual reproduction
Two parents contribute genetic information to form a genetically unique offspring
Why is reproduction important?
- Competitively propagating a species/genetics
- Integral for evolution (improving fitness for survival so that the most fit survives and reproduce )
List all the forms of asexual reproduction
- Binary fission
- Budding
- Gemmules
- Fragmentation
- Regeneration
- Sporulation
- Parthenogenesis
- Vegetative Propagation
- Apomixis
Binary fission
This is the simplest and most common form of reproductions seen in bacteria and archaeans (prokaryotes). In this, the parent cell duplicates its DNA to form 2 daughter cells that take a share of all cellular components
- quite rapid
- identical to parent
Binary fission can also occur in Eukaryotic like amoebae
Budding
In this form, growths that emerge from the body of the organism form offspring that can then break off
- This can happen in single celled eukaryotes such as yeast
Gemmules
In this form, gemmules (internal buds) represented by a specialized group of cells are released to develop into offspring. In certain cases, gemmules can withstand harsh environmental conditions
Fragmentation
In this form, the body of the parent can break into distinct pieces intentionally, each of which can develop into an offspring
- Planarians can reproduce by fragmentation and it can also be forced if the organism was cut in half
Regeneration
In this modified form of fragmentation, when a part becomes detached from the parent, it can grow and develop into a completely new individual
- In sea stars, lost arms can develop into new sea stars
Sporulation
In fungi, green algae, and molds, a type of reproduction is via formation of spores. These are small packages of genetic material identical to the parent surrounded by a tough coat that helps them survive harsh environmental conditions
- Releases spores that are blown into the wind
- Releases a large quantity to ensure some of them grow
Parthenogenesis
This refers to development of an egg into offspring without the need for fertilization (clonal reproduction). Most organisms that reproduce with this method can also reproduce sexualy. It normally occurs in water fleas, most kinds of wasp, bees, and ants but vertebrates rarely reproduce like this
Virgin births
As seen in the California condor has been recorded in other birds, lizard, snakes, sharks, rays and other fish species
Vegetative Propagation
This is a phenomenon by which offspring grow from a part of the plant.
- Ginger (rhizome) can grow under the soil
- Allium, tulips (bulbs)
- Crocuses
- Potatoes
- Grass (stolons) branches that appear to run along the ground level, but they are able to anchor, grow roots. When the branch is severed, they can form independent plants and spread
- Offspring from a leaf edge on the ground
Apomixis
This is a phenomenon by which there is a clonal reproduction, through seeds. This includes parthenogenesis, but can also result in haploid plants which means that these plants intended to produce sexually and underwent the gametogenesis process, but then still ended up reproducing asexually because there was no fertilization or 2 parents. There are also other vegetative methods that can be classified under this form asexual reproduction
Diploid
2n chromosome number, is a terminology used in organisms that reproduce sexually. This is contribution from the paternal (1n) and maternal (1n) gametes that form the individual
Haploid
These gametes are considered haploid because they only have 1n or half of the number of chromosomes that the diploid.
Meiosis
- We have the same diploid genome with 2 copies of the chromosome
- DNA replication
- Then, there’s the opportunity to crossover and exchange genetic material between these sister chromatids
- Then, we have the separation into 2 daughter cells
- Then, there’s a second division where we have the centrioles pull across each of these duplicated chromosomes to form 4 gametes
- Start with a diploid cell but end with 4 haploid gametes
- Because these gametes are haploid, they are able to fuse with other haploid gametes and regain their deployed status
Sexual reproduction in the sporophyte
- The plant is the mature sporophyte and under the leaves, it has these sporangium which is the site of meiosis
- When meiosis occurs, we end up with spores that are haploid that are sent out to the environment
- These spores develop into the mature gametophyte
- These gametophyte develop into the mature gametophyte
- These gametophyte develop regions that contain antheria (sperm) and archegonia (eggs)
- The sperm are released into the environment and seek out archegonia to fertilize and form a zygote
- New sporophyte –> mature sporophyte
