Neurology & neuroscience Flashcards
What is the telencephalon also known as?
Cerebral hemisphere
What are the ridges on the telencephalon called?
Gyri
What are the valleys on the telencephalon called?
Sulci
What are the 4 functionally distinct regions or lobes of the hemispheres called?
- Frontal: Responsible for executive functions such as personality
- Parietal: Contains the somatic sensory cortex responsible for processing tactile information
- Temporal: Contains important structures e.g- hippocampus (short term memory), the amygdala (behavior), and Wernicke’s area (auditory perception & speech)
- Occipital: Processing of visual information
What are the 3 main structures of the brainstem in descending order?
Midbrain
Pons
Medulla
Where is the brainstem and what is its overall function?
Dorsal region of CNS
Role in motor coordination, balance, and posture
What are the 4 different possible morphologies of neurons?
- Unipolar
- Pseudo-unipolar
- Bipolar
- Multipolar
- Pyramidal cells
- Purkinje cells
- Golgi cells
What is another name for the cell body?
Soma
What is the most abundant cell type in the CNS?
Astrocyte
What is an astrocyte and what is its function?
Structural cells that play a role in cell repair, synapse formation, neuronal maturation, and plasticity
What are the functions of Oligodendrocytes and Schwann cells?
Myelin producing cells
What is the difference between Oligodendrocytes and Schwann cells?
Oligodendrocytes work in CNS
Each Oligodendrocyte is capable of myelinating a number of axons
vs
Schwann cells work in the PNS
A Schwann cell only myelinates a single axon segment
What is a Microglial cell?
A cell that is similar to macrophages and performs immune functions in CNS
What is an Ependymal cell?
Epithelial cells that line the fluid-filled ventricles regulating the production and movement of cerebrospinal fluid
What is the resting membrane potential of neurons?
Around -70mV
If the membrane potential is too negative, what is the cell said to be?
Hyperpolarised
If the membrane potential becomes more positive, what is the cell said to be?
Depolarised
What are the 4 major physiological ions that control the Resting Membrane Potential (RMP)?
K+
Na+
Cl-
Ca2+
What are the relative concentrations of K+, Na+, Cl-, and Ca2+ extracellularly?
Higher Na+
Higher Cl-
Lower K+
Higher Ca2+ (High conc. gradient)
Explain how K+, Na+, Cl-, and Ca2+ are involved in the generation of an action potential?
Influx of Na+ via voltage-gated sodium ion channels (VGSC) leads to further depolarisation
Explain how the ions are involved in the restoration of the resting membrane potential?
Voltage-gated potassium ion channels (VGKC) opens at a slower rate, leading to efflux of K+ from the cell which repolarises the membrane
How is the Na+/K+ ATPase involved in restoring the ion gradients?
Resting configuration - Na+ enters vestibule & upon phosphorylation, ions are transported through the protein against conc. gradient
Active configuration - Na+ removed from the cell and K+ enters the vestibule against conc. gradient. The pump returns to resting configuration and K+ is transported back into the cell
What is the process by which AP spreads along the axon also known as?
Cable transmission
What is meant by saltatory conduction?
AP ‘jumps’ between nodes of Ranvier to get to the pre-synaptic terminal faster
What is the function of Myelin in the traveling of the AP?
Prevents AP from spreading because it has high resistance and low capacitance
What are the Nodes of Ranvier?
Small gaps of no myelin intermittently along the axon
What happens when the action potential reaches the Synapse?
AP opens voltage-gated Ca2+ channels (VGCC) at the presynaptic terminal
Ca2+ influx down conc. gradient → exocytosis of vesicles containing neurotransmitter
Neurotransmitter released into the synaptic cleft
The neurotransmitter binds to receptors on the postsynaptic membrane
Receptors modulate the post-synaptic activity
Enzymes (cholinesterase) break down neurotransmitter to be uptaken again by pre-synaptic cleft
Or the neurotransmitter could be recycled by transporter proteins on the pre-synaptic cleft
How does an action potential travel across a neuromuscular junction?
Action potential propagated along the axon (Na+ and K+) until it reaches the voltage-gated calcium channels
Ca2+ influx at the presynaptic terminal causes exocytosis of vesicles containing ACh into the synapse
ACh binds to nicotinic ACh receptors (nAChR) on skeletal muscle → change in end-plate potential (EPP). EPP becomes a minimal EPP leading to quantal ACh release
Activation of nAChR leads to depolarization of the sarcolemma (skeletal muscle membrane) and the creation of an AP that travels through T-tubules (continuous with sarcolemma & closely connected to the sarcoplasmic reticulum).
Where is the sarcoplasmic reticulum?
Surrounding myofibrils
What is the function of the sarcoplasmic reticulum and what effect does it have?
Ca2+ storage → Ca2+ release following sarcolemma depolarisation
Ca2+ → myofibril contraction & muscle contraction
What is Myasthenia Gravis (MG) and what does it cause?
Autoimmune disorder: antibodies directed against ACh receptor
Causes fatigable weakness (becomes more pronounced with repetitive use)
What is the Nernst equation used to calculate?
Equilibrium potential
What is the Nernst Equation?
E=(RT)/(zF) x ln(X2/X1)
R = Gas constant T = Temperature in Kelvin z - charge on ion F = Faraday's number - charge per mol of ion ln = natural logarithm X2 = Intracellular ion concentration X1 - Extracellular ion concentration
What is botulism and what does it cause?
Disorder of the neuromuscular junction caused by the botulinum toxin (BTx), and causes irreversible disruption of stimulation-induced Ach release from the presynaptic terminal.
What is Lambert-Eaton myasthenic syndrome (LEMS) and what does it cause?
An autoimmune disorder where antibodies are directed against VGCCs.
What does the Goldman-Hodgkin-Katz equation calculate?
The membrane potential of the cell if the concentration of an ion inside and outside the cell and the permeability of the membrane to that ion are known.
Stated as Em
P= permeability/channel open probability, and i and o indicate if the ion is in or out of the cell.
Describe the steps of an action potential
- Resting membrane potential -> Permeability K+> Permeability Na+
- Depolarization -> Stimulus depolarises membrane potential to move it in the positive direction towards the threshold.
- Upstroke - After the threshold has been reached, VGSCs open quickly so Na+ enters the cell down the electrochemical gradient and VGPCs open slowly so K+ leaves the cell down the electrochemical gradient. Membrane potential moves towards Na+ equilibrium potential
- Repolarization -> Decreased permeability of Na+ as VGSCs close. Increased permeability of K+ as VGPCs open so K+ leaves cell down its electrochemical gradient. Membrane potential moves towards K+ equilibrium potential. At this point, there is an absolute refractory period.
- After-Hyperpolarisation -> At rest, VGPCs are still open, so K+ leaves the cell down its electrochemical gradient, causing hyperpolarization. Membrane potential moves closer to K+ equilibrium so some VGPCs then close and membrane potential returns to resting potential.
What is the absolute refractory period?
Period where VGSCs can’t be opened again and so a new action potential cannot be triggered
What is the relative refractory period?
Period of time where you need a stronger than normal stimulus to trigger another action potential
Due to hyperpolarization, more of a depolarization is required to reach the threshold and then cause another action potential
How is an action potential an example of positive feedback?
Once the depolarization occurs so that it is above the threshold potential, VGSC open
Increasing permeability which increases an influx of Na+
This causes more depolarisation repeating the cycle of opening VGSC to increase Na+
What does the propagation distance and velocity of the AP along the axon depend on?
Myelin thickness - Linear relationship between conduction velocity and myelin thickness
Diameter of axon - Larger diameter, faster traveling of action potential due to less resistance (conduction velocity proportional to square root of axon diameter)
What is the best definition of pharmacology?
A chemical substance that interacts with a specific target within a biological system to produce a physiological effect
What 3 questions should you ask yourself when considering the pharmacology of a drug?
What is the target for the drug?
Where is the effect produced?
What is the response produced after interaction with this target?
How can you determine the safest drug based on the dosage of the drug?
The safest drugs are those where there is a large difference between the dose required to induce the desired effect and the dose required to induce side effects/adverse effects
What are the 4 main classes of proteins that drugs usually target?
Receptors
Enzymes
Transport Proteins
Ion Channels
What class of protein does Salbutamol act on?
Receptor - Beta-2 Adrenergic receptor in lung
Why might selectivity be more important for drugs than endogenous compounds like dopamine?
Neurotransmitters are very specifically delivered to their drug target, e.g released by certain post-synaptic neurons to react directly with their receptors
Drugs would need to pass through the bloodstream to be distributed to a certain tissue, however, it could enter any tissue and so does not directly interact with the target
What is the definition of a side effect?
An effect produced by the drug that is secondary to the intended effect
What is meant by an adverse effect?
If that side effect has negative health consequences
What can you call a drug that tries to mimic the effects of dopamine?
Dopamine receptor agonist
As the dose of a certain drug increases, what is the effect on the selectivity of that drug?
Decreases
What is meant by the off-target effect of a drug?
Adverse effects as a result of modulation of other targets; these may be related biologically or totally unrelated to the target of interest
Which kind of effect increases as the dosage of a drug increases?
Off-target effects
What is meant by the on-target effect of a drug?
Exaggerated and adverse pharmacologic effects at the target of interest in the test system
What is synaptic transmission?
Information transfer across the synapse requiring the release of neurotransmitters and their interaction with postsynaptic receptors
List 4 characteristics of synaptic transmission
Rapid timescale
Diversity
Plasticity
Learning and memory
List the basic structures of the neuron
Dendrites (contains spines on the surface)
Soma (cell body)
Axon
Synaptic terminal
What is the purpose of spines being present on the surface of dendrites?
Protein molecules that increase the surface area for information reception
What neuronal structure integrates all the information coming into a neuron?
Soma (cell body)
What is required for communication between neurons?
Neurotransmitter release (synaptic transmission)
What are the 3 steps that occur when a dendrite of one neuron receives an electrical impulse from another neuron?
Information reception at dendrites
Integration (occurs at the soma)
Rapid transfer (action potential) - impulse passed along axon towards the synaptic terminals
What type of neurotransmission occurs at the synapse?
Chemical neurotransmission
Which specialized structures is neurotransmission restricted to?
Synapses
What does a synapse consist of?
Presynaptic nerve ending/terminal
Gap (synaptic cleft) ~ 20-100nm
Postsynpatic regions (dendrite or cell soma)
List 3 types of molecules that can be neurotransmitters and include examples of each
Amino acids - glutamate, gamma-aminobutyric acid (GABA), glycine
Amines - noradrenaline and dopamine
Neuropeptides - opioid peptides
What happens when a CNS synapse is activated?
Arrival of the action potential - spreads across pre-synaptic nerve terminal
Depolarisation of whole terminal (Na+ influx followed by a K+ efflux)
Activates VGCC to open allowing Ca2+ to flow into the presynaptic terminal (down its concentration gradient)
Activates exocytotic release of neurotransmitter into synaptic cleft → diffuses across the synaptic cleft and makes contact with receptors (in this case excitatory receptors) on the post-synaptic terminal
Depolarization of the post-synaptic terminal leads to th generation of another action potential
Inactivation of neurotransmitter as it is returned to the pre-synaptic terminal back into its vesicle where it can be reused
Sodium-potassium pump returns membrane potential to normal (separate from synapse pathway)
What are the methods by which the neurotransmitter can be returned to the pre-synaptic terminal after depolarizing the post-synaptic terminal?
Re-uptake of neurotransmitter via a protein transport channel
Enzymatic degradation within the synaptic cleft (e.g. acetylcholine is broken down by acetylcholinesterase)
Outline the process of neurotransmitter release
Membrane depolarization leading to the opening of Ca2+ channels
Ca2+ influx leading to docking of synaptic vesicles (SVs) onto the presynaptic membrane
They are primed and undergo fusion → they open and neurotransmitter is released via exocytosis into the synaptic cleft
The empty vesicle buds off (budding) and recycles forming new vesicles that can be reused (endocytosis)
What 2 things does neurotransmitter (NT) release require?
Calcium influx and RAPID transduction
electromechanical transduction - links the Ca2+ influx with NT release
