1.0 Introduction to Neurones Flashcards
What is the function of the medulla and pons?
Control regulatory systems for basic function (CVS/resp)
What is the function of the cerebellum?
Planning complex movements
What is the function of the midbrain?
Dorsal surface = tectum<br></br>Contains superior and inferior colliculi <br></br><br></br>Superior colliculi = visual processing<br></br>Inferior colliculi = auditory processing
What is the function of the thalamus?
Closely linked to cerebral cortex (specific areas of cortex are linked to thalamus)
What is the function of the hypothalamus?
Regulator of homeostasis<br></br>Controls endocrine/ANS/behaviour
What is the function of the cerebral cortex?
Largest part of brain<br></br><b>Primary cortical areas</b> = specialised for processing one modality<br></br><br></br><b>Association cortices</b> = receive and associate info of many modalities
What is the function of the basal ganlia?
Group of nuclei under the cortex<br></br>Associated with learned selection and expression of beneficial beavhiour for a given circumstance
What is the function of the amygala?
Assessment and learning of the <b>emotional significance</b> of given sensory info
Function of Soma
Soma = cell body<br></br>It is the metabolic centre of the cell<br></br>Contains nucleus and ER<br></br>Gives rise to dendrites and axons
Function of Dendrites
Receive incoming signals from other nerve cells
Function of Axon Hillock
Specialised part of the soma that connects it to axon. Action potentials are initiated here because it has the lowest threshold potential
Function of Axon
Carries signals to other neurons (can convey singles from 0.1mm to 2m)
For the following ions:<br></br>1) Sodium<br></br>2) Potassium<br></br>3) Chloride<br></br>4) Calcium<br></br><br></br>What is the internal concentration, external conc. , valence, and equilibrium potential?
“<div><img></img></div>”
What is the Nernst potential?
Membrane potential at which there is no net flux of that ion across the membrane<br></br>Depends on <b>chemical</b> and <b>electrical</b> gradients
What is the Nernst equation?
“<div><img></img></div>”
At rest, what ion is the membrane mainly permeable to?
Potassium (K⁺)
What is the Donnan equilibrium?
If a membrane is permeable to both K⁺ and Cl⁻, they will move across until their concentration gradient is balanced by membrane potential.<br></br>Therefore if <b>equilibrium</b> is reached:<br></br>[K⁺]i x [Cl⁻]i = [K⁺]o x [Cl⁻]o
What two secondary active processes are used to extrude Cl⁻:
1) KCC2<br></br>2) NDCBE<br></br>Therefore ECl is usually more negative than membrane potential
What two neurons have increased internal [Cl⁻]?
1) Developing neurones<br></br>2) Adult olfactory receptor neurones<br></br><br></br>Therefore opening of Cl⁻ channels → outward (excitatory) current
3 mechanisms by which calcium is extruded from the cell?
1) ATP-fuelled Ca²⁺ pump<br></br>2) NCX<br></br>3) NCKX
What are the steps for neurotransmitter release?
1) AP reaches nerve terminal<br></br>2) Opening of voltage gated Ca²⁺ channels<br></br>3) ↑ [Ca²⁺]i<br></br>4) Fusion of vesicles with membrane
What proteins are needed for vesicle fusion with plasma membrane?
1) <b>v-SNAREs</b> (synaptobrevin)<br></br>2) <b>t-SNAREs</b> (SNAP-25 and Syntaxin)<br></br>3) Synaptotagmin (Ca²⁺ sensor)
What are the stages for vesicle fusion with plasma membrane?
1) Vesicle <b>docks</b> at presynaptic active zone<br></br>2) Vesicle is <b>primed</b> by close association between v-SNAREs and t-SNAREs<br></br>3) Vesicles <b>fuse</b> with plasma membrane in <b>Ca²⁺ dependent manner</b>
3 criteria needed for a substance to be considered a neurotransmitter
1) Present at pre-synaptic terminal<br></br>2) Released during stimulation<br></br>3) Must have same effect when exogenously applied
What are the two types of neurotransmitter receptors?
<b>Ionotropic</b><br></br>- Direct mechanism of action<br></br>- Ionic channels<br></br>- Rapid<br></br>- Can allow Ca²⁺ influx<br></br><br></br><b>Metabotropic</b><br></br>- Indirect mechanisms<br></br>- Uses 2nd messengers<br></br>- Effect is usually via α-subunit bound to GTP<br></br>- Can also be due to βγ (usually acting on K⁺ channels)<br></br>- Results in <b>amplification</b>
List 3 amino acid neurotransmitters:
Glutamate<br></br>GABA<br></br>Glycine
List 5 biogenic amine neurotransmitters:
ACh<br></br>NA<br></br>Dopamine<br></br>Serotonin<br></br>Histamine
List 2 purine neurotransmitters:
ATP<br></br>Adenosine
List 2 gaseotransmitters:
NO<br></br>CO
What is the mechanism of the NMDA receptor?
<b>Glutamate ionotropic receptor</b><br></br>Causes depolarisation<br></br>Permeable to Ca²⁺ + Na⁺<br></br>At -ve potentials channel is blocked by Mg²⁺<br></br>When depolarised, membrane is relieved and Na⁺ + Ca²⁺ can pass
What is the mechanism of the AMPA receptor?
<b>Glutamate ionotropic receptor</b><br></br>Causes depolarisation<br></br>Permeable to Na⁺ + K⁺<br></br>Impermeable to divalent ions
What is the mechanism of the β adrenergic receptor?
<b>Adrenergic metabotropic recetor</b><br></br>Gαs coupled → activation of adenylyl cyclase → ↑cAMP
What is the mechanism of the nACH receptor?
<b>ACh ionotropic receptor</b><br></br>Causes depolarisation<br></br>Permeable to Na⁺ + K⁺
What is the mechanism of the Glycine receptor?
<b>Glycine ionotropic receptor</b><br></br>Causes hyperpolarisation<br></br>Permeable to Cl⁻
What is the mechanism of the GABA-A receptor?
<b>GABAionotropic receptor</b><br></br>Causes hyperpolarisation<br></br>Permeable to Cl⁻ + K⁺
Long sensory receptors vs short sensory receptors
“<div><img></img></div>”
Direct transduction vs indirect transduction
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Define accessory structures:
Structures that can modify the sensitivity, selectivity, time course or response of a receptor
Examples of accessory structures:
1) Lens (focuses image onto retina)<br></br><br></br>2) Lamellae in Pacinian corpuscules (allow rapid adaptation)
Ionic basis of excitatory post-synaptic potential
Glutamate ion channel (permeable to Na⁺ + K⁺)<br></br>Reversal potential = 0mV<br></br>Opening of channel → membrane potential is drawn closer to reversal potential and depolarizing the cell
Ionic basis of inhibitory post-synaptic potential
Caused by release of glycine or GABA<br></br><br></br><b>Glycine</b><br></br>↑ Cl⁻ conduction → hyperpolarisation<br></br>Reversal potential = -80mV<br></br><br></br><b>GABA</b><br></br>↑ Cl⁻ + K⁺ conductance → hyperpolarisation
Type I vs Type II synaptic inputs
<b>Type I</b><br></br>Excitatory<br></br>Found on spine and shaft<br></br>Round vesicles<br></br><br></br><b>Type II</b><br></br>Inhibitory<br></br>Flat vesicles<br></br>Found on soma
Where does initiation of AP occur?
Axon hillock (this region has the lowest threshold)
What is space constant?
“Distance at which 63% of Vmax is lost<br></br>Larger space constant favours <b>spatial summation</b><div><br></br></div><div><img></img></div>”
What is time constant?
“Time taken for 63% of Vmax to be lost<br></br>Larger time constant favours <b>temporal summation</b><div><br></br></div><div><img></img></div>”
What is spatial summation?
When two or more APs arrive simultaneously from <b>different</b> pre-synaptic neurons. Post-synaptic potentials add together.<br></br>Allows control as inhibitory and excitatory inputs can be collated together and APs only fire is threshold is reached.<br></br><b>↑ space constant favours spatial summation</b>
What is temporal summation?
When two or more APs arrive in rapid succession from <b>same</b> pre-synaptic neuron. Post-synaptic potentials add together.<br></br><br></br>Allows APs to initiate in situations of high frequency stimulation of the receptor (successive excitatory post-synaptic potentials take membrane potential to threshold)<br></br><br></br><b>↑ time constant favours temporal summation</b>
What is shunting inhibition? (what is significance of location of inhibitory and excitatory inputs?)
When an excitatory current and an inhibitory current synapse on the <b>same</b> dendrite, the current becomes <b>divided</b><br></br><br></br>Much less excitatory current is available than would be expected (↓ inhibitory current is needed to dissipate excitation)<br></br><br></br>This is why excitatory inputs are further away on dendrites compared to inhibitory inputs on soma
What is presynaptic inhibition?
<b>Axo-axonic synapse where inhibitory neuron synapses with axon of another neuron and prevents neurotransmitter release</b><br></br>This offers powerful control over synaptic transmitter release<br></br>Inhibitory signal must occur at same time as action potential<br></br>Cl⁻ + K⁺ channel opening → ↓ AP → ↓ Ca²⁺ influx → ↓ neurotransmitter release → preventing neuron from generating EPSP
What is the A current?
<b>Inactivating K⁺ current</b><br></br>Inactivated with depolarisation<br></br>Function = spaces spikes in spike train (it leads to a graded change in frequency that is dependent on the initial depolarising current*<br></br>Ik - takes membrane potential back to resting levels<br></br>A current - keeps membrane potential at resting levels by opposing depolarising current. But a greater depolarisation → quicker inactivation of the A current → more frequent spikes
What are the different Ca²⁺ channels?
<b>T</b><br></br>Transient<br></br>Threshold = -65mV<br></br>Inactivates with moderate speed (20-50ms)<br></br>Function = Rhythmic burst firing<br></br><b>L</b><br></br>Long lasting<br></br>Threshold = -20mV<br></br>Inactivates with very slow speed (>500ms)<br></br>Function = Synaptic transmission + dendritic Ca²⁺ spikes<br></br><b>N</b><br></br>Neither<br></br>Threshold = -20mV<br></br>Inactivates with moderate speed (50-80ms)<br></br>Function = synaptic transmission + dendritic Ca²⁺ spikes<br></br><b>P</b><br></br>Purkinje<br></br>Threshold = -50mV<br></br>Function = dendritic Ca²⁺ spikes
What is divergence?
One presynaptic neuron synapses with multiple post-synaptic neurons
What is convergence?
<b>Multiple presynaptic neurons synapse with one post-synaptic neuron</b><br></br>Can be important for excitation as one EPSP may not be enough to reach threshold
What is subliminal fringe?
“Excitatory input to a motor neuron pool can cause some neurons to reach threshold (via spatial summation)<br></br>Some neurons are excited but not enough to reach threshold. These are called the <b>subliminal fringe</b> (Neurons within the motor neuron pool that are stimulated, but not sufficiently to reach firing threshold)<br></br>Overlap of 2x subliminal fringes → <b>summation in a supra-linear manner</b><div><br></br></div><div><img></img></div>”
What is feedforward inhibition?
Pathway to antagonist is inhibited when agonist pathway is stimulated<br></br>(e.g. inhibition of extensor muscles when flexors are stumulated)
What is feedback inhibition?
Excitatory cell contains an inhibitory interneuron which inhibits its own firing (and that of synergistic neurons)<br></br><br></br>Example = Renshaw cell of spinal cord (stabilises motor neuron firing)
Describe the flexor withdrawal reflex
Stimulation of cutaneous nociceptors →<br></br>1) Inhibition of extensors<br></br>2) Stimulation of flexors<br></br>Above two responses → withdraw limb from harm
Describe to crossed extensor reflex
Nociception → <br></br>1) Stimulation of contralateral extensors<br></br>2) Inhibition of contralateral flexors<br></br>Above two responses → provides support
What is synaptic facilitation?
Repeated stimulation → enhanced post-synaptic potential <br></br>Due to ↑ Ca²⁺ within the terminal → ↑ transmitter release
What is synaptic depression?
Repeated tetanic stimulation → depression<br></br>Due to depletion of vesicle pool
What is post-tetanic potentiation?
Following cessation of tetanic stimulation + recover from depression, the post-synaptic response is <b>transiently</b> enhanced<br></br>This is due to actions of Ca²⁺ on vesicle priming (can persist for several minutes after stimulation)
What is long-term potentiation?
Very long lasting changes in excitability following stimulation. Can occur when 2 inputs are stimulated at the same time
What is Hebb’s Law?
An input is strengthened when it plays a role in firing of the target cell
What is the Bruce Effect?
<b>Female mouse learns the odour of a familiar male mouse who mated with her. If, within a few days, the pregnant mouse is exposed to the odour of an unfamiliar male, the fetus is aborted</b><br></br><br></br>However, exposure to the pheremones of the mated male does not terminate pregnancy<br></br>Mechanism:<br></br>1) A specific mitral cell is activated by the odour of the familiar male, and releases glutamate in response<br></br>2) Glutamate stimulates adjacent granule and peri-glomerular cells, and granules cells promote reciprical inhibition of the stimulating mitral cell with GABA<br></br>3) During mating, noradrenaline acts on adrenergic receptors on both the granule cell and mitral cell to reduce GABA release, such that the specific mitral cells responding to the mated male odour is strongly activated<br></br>4) Following this strong activation, inhibition of the synapses stimulated by the male odour is strongly enhanced, which prevents pregnancy block
