Lecture One : Introduction to Neuroscience
- Neurons are cool. That’s the entire basis of this course!
- The mitochondria is the powerhouse of the cell
Lecture Two : The Resting Membrane Potential
- The movement of ions at their electrochemical gradient
- There are more positive charges on the outside of the membrane so the charges want to move DOWN (from areas of high to low concentration) their
concentration gradient into the cell where there is less of a positive charge. - We do this by diffusion! Diffusion occurs when concentration gradients exist across a membrane and ions channels that are permeable to specific ions are open.
- Uneven distribution of ions across the neuronal membrane
- This helps establish a concentration gradient and the membrane potential. - For example, we know that Potassium (K+) is more concentrated on the inside of the cell and Sodium (Na+), Calcium (Ca2+) and Chloride (Cl-) are more concentrated outside of the cell.
- Neuronal Membrane Proteins for Ionic Movement We also discuss several other topics like kinesiology textbook
- Three different types of channels (or ways to transport ions across the membrane) - Ion Channels
- Allow the passage of ions across the membrane DOWN their
- Highly ion selective
- Opening/gating mechanism
- Ion Pumps
- Transport ions across a membrane at the expense of metabolic
energy (ATP breakdown) which moves ions AGAINST (from
areas of low to high concentration; also called “UP” ) their
- Coupled Transporters (also called cotransporters) We also discuss several other topics like acct 2301 utd
- The energy gained from transporting one species down the
gradient is used to transport another species up the gradient
- The movement of potassium releases some sort of
energy and that is sufficient enough to allow the
movement of chloride down its concentration
- Relative Ion Permeability of the Membrane at rest determines the resting membrane potential
- The resting membrane potential is set at -70mV because it's closer to the equilibrium potential of potassium. This is because the membrane is more permeable to potassium ions, which means it moves more potassium ions across the channel. Since potassium is a positive ion and it naturally moves out of the cell, we are removing positive ions. If we remove positive ions, the inside is becoming more negative. That is why the equilibrium potential is more negative and the resting membrane potential reflects that.Don't forget about the age old question of Why have cities been connected to the development of civilization, generally?
- So, it's the ion permeability of the membrane that determines the resting membrane potential!
Lecture Three : Action Potential Generation and Propagation
- Summary : Voltage-Gated Na+ and K+ channels
- Involved with generating an action potential. It’s the movement of the opening and closing of these channels that help generate the different phases of the action potential.
- Sequential , voltage dependent changes in Na+ and K+ conductances account for action potentials
- At first, voltage gated Na+ channels open (very fast) and K+ channels open (very slow).
- The RMP depolarizes from -70mV to the threshold of -40mV.
- Once this threshold is reached, we can generate an action
potential. This causes the open voltage gated Na+ channels to
allow inward sodium movement whereas the open voltage K+
channels allow outward potassium movement.
- Voltage gated Na+ channels stay open for less than a
millisecond then inactive, whereas the voltage gated K+
channels stay open much longer as the membrane remains
- Regenerative Conduction of Action Potentials
- There’s generally one direction that action potentials will flow and it is due to the repolarization (or hyperpolarization) phase of the action potential. If you want to learn more check out motorcucles
- The A portion is where the action potential occurs. When the energy is released form that action potential, it flows both ways (backwards towards
B and forward towards Z). The reason why we don't get the backward
generation is due to the hyperpolarization. We’re making the membrane potential more negative so it’s making it harder to reach the threshold to make an action potential.
- Saltatory Conduction of Action Potentials
- The myelinated portion acts as insulation. If you want to learn more check out csu bmb
- In the myelinated portion we have passive conduction of depolarization which allow the myelin to increase the speed of conduction.
- Just enough energy to reach the next NOR
- In between each myelin sheath is an unmyelinated portion (called the Node of Ranvier).
- In the NOR, we have a lot of voltage gated NA+ channels that are
concentrated to produce the action potential generation.
Lecture Four : Synaptic Transmission I
- The presynaptic active zone is a highly organized structure
- Different parts allow the synaptic vesicle to bind to the presynaptic membrane area, allowing for neurotransmitter release. There are Ca2+ channels that allow for calcium binding. Once calcium is bound, we start this cascade on the inside where synaptotagmin, which is attached to the synaptic vesicles will bind to the SNARE complex and as they are attached to each other they pull. The pulling mechanism allows for the bringing of the synaptic vesicle to the membrane. - Neurotransmitter Reuptake
- The exocytosis of the synaptic vesicles where neurotransmitters are released in the synaptic cleft. Glia cells will take up whatever is left over. Once we have these neurotransmitters that bind to receptors, they can't stay in the synaptic cleft forever so they have to get “reuptaken” and recycled. Don't forget about the age old question of latn 1003 class notes
- Ionotropic Neurotransmitter Receptor
- Neurotransmitter-gated ion channel
- Opens when neurotransmitter binds to receptor
- Directly permeates ions in postsynaptic membrane
- Fast postsynaptic response: postsynaptic potential (PSP)
- Less ion-selective than voltage-gated ion channels
- Characteristics of Ionotropic Receptors
- More direct
- Ionotropic Glutamate Receptors and Excitatory Postsynaptic Potential (EPSP) - Help generate EPSPs
- Inotropic positive receptors use glutamate as the major excitatory
neurotransmitter. Two different types :
- Faster and movement is made through passive of ions
- Only requires glutamate
- Slower due to their structure.
- While they do permeate K+, they are highly permeable to Ca2+
meaning they move calcium more often.
- There is a magnesium block on the inside
- While AMPA receptors are able to just pass ions through,
the NMDA have a magnesium ion that is within the
channel and its the depolarization of the membrane
potential that pops off that magnesium, allowing for the
movement of Calcium and other ions.
- Requires glutamate and depolarization
- Ionotropic GABA Receptor (GABAa) & IPSP
- For IPSP, GABA is the main inhibitory neurotransmitter
- GABAa refers to the ionotropic receptor
- GABAb refers to the metabotropic receptor
Lecture Five : Synaptic Transmission II
- Spatial and Temporal Summation of EPSP
- Spatial Summation
- Summing up two different EPSPs form two different branches. As they travel down the dendritic tree to get to the soma, they add to each other. This results in a larger traveling potential.
- Temporal Summation
- Focus on one dendritic branch but two EPSPs are generated one after another. When these two EPSPs are generated, they travel down the
dendritic tree. This traveling EPSP is adding on to each other. Before the first EPSP ends, the second one builds upon it to add for this continuing traveling of the EPSP.
- EPSP summation in the soma : sufficient EPSP summation induces action potential firing in postsynaptic neurons
- EPSP summation in dendritic spines : sufficient EPSP summation activates NMDA-type glutamate receptors by relieving voltage-dependent Mg2+ block
- Synaptic Inhibition - summation of EPSPs and IPSPs
- This is an EPSP. At -70mV we are at rest. An IPSP is generated and we have this downward deflection of the membrane potential. Were making the membrane more negative!
- This an EPSP where we get a depolarization that allows us to reach threshold. Once we reach threshold, we produce an action potential and go back down to resting membrane potential.
- If we were to add up the EPSP and the IPSP we would not be able to reach threshold to reach EPSP because they would cancel each other out.
- Metabotropic Neurotransmitter Receptor
- Metabotropic Neurotransmitter Reporters trigger G protein receptors
- The major thing is that metabotropic receptors are G protein coupled receptors. G protein means that they are trimeric (have three subunits : alpha, beta, gamma). - At resting state we have a g protein that’s coupled to the metabotropic
- Once we get the ligand to bind, we get this association of the G
protein exchanging the GTP for GDP
- This activates the G protein complex. This allows beta
gamma to dissociate and bind to or directly influence the
target protein (usually an ion channel). We also have the
alpha subunit that triggers the second messenger.
- Second Messenger Systems (FOCUS ON WHAT’S HIGHLIGHTED)
- Presynaptic Facilitation and Inhibition
- Presynaptic Facilitation (for example serotonin) :
- As an excitatory neurotransmitter binds to serotonin, the serotonin
receptor is inhibiting the transmembrane potassium protein channel. If it
prohibits the potassium from flowing out, were not hyperpolarizing the
cell because we're not losing ions to the outside thus, inhibiting the release
- Presynaptic Inhibition (for example from a GABAergic neuron)
- A GABAergic neuron releases GABA and is taken up by the GABAb
receptor because it is metabotropic receptor. GABAb takes up the GABA
neurotransmitter and we excite the potassium channels to allow the
outward movement of potassium. At the same time, we are inhibiting
calcium channels to enter the cell allowing neurotransmitters to be
Lecture Six : Sensory Systems
- Mechanotransduction in the hair cells
- Mechanotransduction - the conversion of a chemical signal to an electrical signal - Hair cells are found in the inner ear and they have these things at the top called stereocilia. Stereocilia are attached together via tip link proteins. So, at rest they are pointing straight up but because they are attached at the top to the tectorial membrane, when the cochlea vibrates that allows a shearing mechanical force. If we are moving the tectorial membrane and the stereocilia are attached, when they move it causes a bending force that moves the tip link proteins and opens up the channels at the top of the stereocilia.
- These channels open because there is a higher concentration of potassium outside of the cell in the endolymph, which is extracellular space.
- This means potassium is going to want to flow to the inside of the
hair cell, ultimately depolarizing it. This depolarization causes
voltage gated calcium channels to open and and once we get an
influx of calcium channels we get neurotransmitter release, mainly
glutamate. This signals the auditory signal
- This is an exception to the movement of potassium ions.
- Sound frequencies are represented as tonotopic map in the Cochlea - The tonotopic map tells us where we vibrate along the cochlea
- At the base of the cochlea the physical properties are thinner and more flexible which allows it to vibrate at higher frequencies. As we move along the cochlea and get to the apex in the middle, the physical
characteristics become more thick and rigid which allows it to vibrate at lower frequencies.
- Organization of the Somatosensory System
- In the skin and muscle fibers, we have receptors that receive a signal that gets transported to the dorsal root ganglion (a collection of cell bodies in the PNS ; sits right outside of the nervous system). Once we reach the spinal cord on the dorsal side, these different type of nerve fibers synapse at specific region within the spinal cord. This is HIGHLY organized.
- Piezo, a mechanotransduction channel
- This is proving that the Piezo is necessary to transmit a signal during some sort of physical stimulation.
- TRP Channels “ temperature, chemical and pain sensation
- Two types:
- Respond to cold or chemical stimulus
- Responds to different types of pain and temperature stimulus
- If you put both channels together, they respond to everything
- Olfactory Transduction pathway and its regulation
- A metabotropic pathway involving second messengers.
- The olfactory sensory neuron receives an odorant. It’s associated with the alpha subunit g protein (G��olf). Once this g protein gets activated it
dissociates and cyclic AMP (cAMP) is involved and it indirectly
influences the CNG (cyclic nucleotide gated ion) channel.
- Mammalian Taste Receptors
- Different flavors have different types of receptors
Lecture Seven : Motor and Regulatory Systems
- Comparison of motor and autonomic output systems
- Motor Output system
- A more direct pathway from the CNS to the effector
- Autonomic Nervous System
- The pathway to the CNS is not as direct because it involve synapses in the PNS
Lecture Eight : Synaptic Plasticity and Memory
- Input - specific LTP in Discriminative Fear Learning (IMPORTANT!!) - This is saying after we have paired the conditioned stimulus and the
unconditioned stimulus response, which means the tone and the shock, after these two have been paired if we present a specific tone, it will illicit the fear response. Whereas if we play a different tone it wont illicit the fear response
- The fear response is discriminative towards certain tones.
- CS+ : The conditioned tone is going to induce LTP
- CS- : The unconditioned tone isn't going to produce LTP
Lecture Nine : Neurotransmitters and Psychiatric Disorders
- Drugs target specific areas that are associated with dopamine receptors - Major depressive disorders have been treated by modulating serotonin in more norepinephrine systems
- Modulating GABAergic inhibition can relive system sof anxiety disorder - GOAL : Associate the excitatory potentials with certain disorders vs the inhibitory targets with their disorders