Flashcards in PA20023 Deck (160):
What receptors are found at excitatory synapses?
Transmitter interacts with receptors largely permeable to K+ and Na+
Eg acetylcholine binds to nicotinic ionotropic receptors at excitatory synapses creating an EPSP
What receptors are at inhibitory synapses?
neurotransmitter can Hyperpolarise the cell, and therefore inhibit from receiving further action potentials.
Hyper-polarisation is through chloride ions
Which is faster at generating an action potential, spatial summation or temporal summation?
When cells are close together, their action potentials can add up to reach threshold; many cells firing at Same time and their action potentials add up.
Whereas temporal is one cell firing in succession to try and generate an AP
Where are purkinje, pyramidal and the motor neurone found?
Purkinje neurones found in cerebellum
Pyramidal neurones found in cortex
Motor neurone is the big neurone in the spinal cord
Are endorphins (endogenous opioids) amino acids, purines, amines or peptide neurotransmitters? what about adenosine?
Endorphins are Peptides
Adenosine is a purine
GABA A and B, which one binds to ionotropic receptors?
GABA a binds to ionotropic
GABA b binds to GPCRs
What are EAATs?
Excitatory Amino acid transporters
They facilitate glutamate reuptake at synapses
Present in glial cell membranes and presynaptic cell membrane to allow glutamate reuptake, stored as glutamine in glial cells
What is monosodium glutamate?
A flavouring In food
It can actually kill some brain cells
Glutamate is involved with exctitoxicity
How is glutamate stored in order to regulate its levels In the CNS?
Stored as glutamine in the Glial cells that sit in between neurones, it is synthesised from glutamine by phosphate activated glutaminase enzyme within a presynaptic cell when it's needed
How does glutamate bind to so many receptors?
It is flexible, it can rotate around its alpha beta and beta gamma bond.
At least 9 different rotamers are possible
The __ elements of ionotropic receptors form the pore. How?
They are part of each of the 4 subunits that form these receptors, they're subunit 2. They associate and bring the subunits all together in an orientation that forms a pore/ channel.
what subunit is present in the AMPA receptor will make it impermeable to calcium? When is it permeable to calcium?
GluA2 subunit present= not permeable to Ca
Homomeric GluA1 receptor= is permeable to Ca
Remember it's also permeable to Na+ in and K+ out
Is NMDA receptor permeable to calcium? How does is compare to the AMPA receptor?
Vastly permeable to calcium, doesn't depend on subunit composition like AMPA.
It lets more calcium in than AMPA even when it is permeable
What is a co-agonist of the NMDA recpetor?
NMDA receptor can only be activated when glycine is present
You need another agonist too; NMDA, glutamate, aspartate
The different properties of the AMPA and NMDA receptors give the fast and slow time course of an EPSP. Which does which?
AMPA: fast on fast off (fast depolarisation)
NMDA: slow on slow off (slow depolarisation)
NMDA receptors are dual gated, what does this mean?
They're both voltage gated an ligand gated.
The channel of NMDA is blocked by Mg2+, which only moves when depolarisation occurs.
NMDA receptor needs both glutamate and depolarisation to work
What effect do mGluRs have on calcium, and on glutamate release?
mGluRs are metabotropic receptors
In presynaptic cells they lead to calcium channel closure, which leads to less glutamate release.
In postsynaptic cells they lead to K+ channel closure.
This leads to reduced K+ efflux out of the cell and slow depolarisation
Also glutamate binding to mGluRs in postsynaptic cell leads to an increased level of intracellular calcium.
What two receptors are involved with glutamate release control?
Presynaptic NMDA (ionotropic) and presynaptic mGluR's.
Presynaptic NMDA r increases glutamate release by increasing calcium influx.
Presynaptic mGLuRs decrease glutamate release by decreasing Calcium influx
GABA is synthesised from _____.
The enzyme that catalyses this is _____.
GABA is further converted into _____, by the enzyme ____.
Drugs acting on these enzymes to increase levels of GABA can be used as _______.
Synthesised from glutamate
By the enzyme glutamic acid decarboxylase
Further converted to succinate
By the enzyme GABA transaminase
Drugs acting on these enzymes can be used as anticonvulsants in epileptics, as GABA is inhibitory.
GABA a receptor (ligand gated ion channel, ionotropic) agonists?
GABA B receptor (GPCR) agonists?
GabaA: agonists are GABA and Muscimol
GABA B: agonists are GABA and baclofen
What is baclofen used to treat?
It binds to GABA B receptors
Inhibits motor neurone activation via the spinal cord
Major side effect: sedation, as baclofen crosses the BBB, inhibits brain activity making you sleepy
Where do benzodiazepines act?
They can be agonist or inverse agonists of the modulator site of GABA A receptors.
They're allosteric modulators, and they bind at the interface between the alpha and gamma subunits of the GABA A receptor.
GABA binds between the alpha and beta subunits
What are benzodiazepines actions?
Bind to GABA A so have inhibitory effects
Anxiety relieving, anticonvulsant and Hypnotic.
Note: they can be agonists, antagonist and inverse agonists
What are etomidate and propofol? Where do they act?
Act at GABA A receptors
Cross BBB and inhibit brain neuronal activity, making you sleepy
What effects do barbiturates and phenobarbital have?
Sedative/ anti convulsive
Calm down muscle activity
They can increase inhibition of nervous activity in the brain to the point of death
Remember barbiturates act on GABA A receptors, they're channel modulators and stimulate the receptor to further inhibit motor pathways
What do Neurosteroids bind to?
Bind to GABA receptors
Metabolites of progesterone & deoxycortisone
Where does ethanol ( Alcohol ) bind in the CNS?
Binds to GABA A receptors
Alcohol has a depressant effect on the CNS
It increases GABAnergic inhibition
Diazepam and lorazepam are Benzodiazepines. How do they make you feel?
They are calming
They are anxiolytics (anti anxiety)
They are NOT sedative
Nitrazepam, flurazepam and temazepam are all Benzodiazepines. How do they make you feel?
So they makes you fall asleep
Used to treat insomnia
Remember benzodiazepines act on GABA A receptors, they're channel modulators and stimulate the receptor to further inhibit motor pathways
Dopamine, 5-hydroxytryptamine, acetylcholine and norepinephrine are all examples of _____________.
They modulate GABA and glutamate
Neuromodulators are not reabsorbed by the presynaptic terminal or broken down. They're neurotransmitters that modulate
How does amphetamine give its stimulatory effects?
It blocks reuptake of Nor adrenaline by NETs( Norepinephrine transporters), amphetamine is also a substrate for these transporters, and can be uptaken into the presynaptic cell, where it can stimulate Nor adrenalin release from vesicles.
Nor adrenaline excites neurones
Amphetamine can therefore increase wakefulness, but can be abused as a performance enhancer
What is L dopa used to treat?
Increases synthesis of noradrenaline
Similar structure to dopamine
More noradrenaline= more Neuromodulators, more muscle movement control.
What drug blocks Vesicular uptake of Nor adrenaline and 5HT and therefore decreases Their levels? What condition can this lead to?
This can lead to depression
Dopamine links to both Parkinson's and schizophrenia. How? What pathways are involved?
Nigrostriatal pathway disrupted without dopamine(from sustantia nigra to striatum) Leads to lack on control of movement- parkinsons
Mesolimbic/ mesocortical pathway (from VTA to cortex & hippocampus) disrupted without dopamine. This pathway is involved with emotional, reward and attention, leads to schizophrenia
What three types of things can be used to treat Parkinson's?
All increase levels of dopamine
What are psychotropics used for?
These block dopamine receptors
Prevents dopamine binding to its receptors
Used to treat manic phases of schizophrenia
But result in Parkinson's like side effects like shakes and tremor due to lack of dopamine
5-HT controls feeding, what does and increase and decrease in 5HT cause?
Increase in 5-HT: loss of appetite, weight loss
Decrease in 5-HT: feeding, hunger, weight gain
(opposite to what you may expect)
What is 5-Hydroxy tryptamine synthesised from?
Hydroxylation by tryptophan hydroxylated
Then decarboxylated by 5HTP decarboxylase
5HT then transported into vesicles by VMAT
Which can become saturated; tryptophan hydroxylase in 5-HT synthesis or tyrosine hydroxylase in noradrenaline synthesis or choline acetyltransferase in Acetylcholine synthesis?
Once it's saturated no more nor adrenaline can be produced from tyrosine
With 5HT and acetylcholine synthesis, the amount of precursor present is raged limiting, not amount of enzyme, as these will not become saturated
How do SSRIs work?
Block the reuptake of 5-HT back into presynaptic cells
What neurotransmitters get transported into their vesicles by VMAT?
VMAT is vesicular monoamine transporter
5 HT, dopamine, noradrenaline
Acetylcholine is NOT
What is each monoamine neurotransmitter involved with (eg arousal, feeding, motivation..)
Dopamine: reward + motivation
5HT: appetites chemical
Acetylcholine : memory/ motivation
Histamine: sleep, feeding, energy balance
What does diphenhydramine (Benadryl) do?
Binds to histamine receptors, it's a H1 antagonist, so its an antihistamine (anti allergy) it's sedating though as it crosses the BBB.
Newer antihistamines don't cross the BBBand are H2 antagonists
What disorders are each of the 4 monoamine neurotransmitters Important in?
Noradrenalin and 5HT important in depression
Dopamine is important in schizophrenia, Parkinson's, and drug addition
Acetylcholine is important in Alzeihmers
How does cocaine have its effects?
Reuptake inhibitor of Noradrenaline and dopamine
Binds to reuptake transporters and blocks them
What axis plays a role in maintaining stress responsiveness?
The hypothalamic pituitary axis
It's releases ACTH (adreno cortico tropic hormone) which stimulates the adrenal gland to release cortisol, a stress hormone, involved with fight or flight response
Cortex, hippocampus, hypothalamus, amygdala, basal ganglia / cerebellum. What are these five parts of the brain involved in?
Cortex: negative cognition: ie having a bad feeling towards something
Hippocampus: Involved with memory
Hypothalamus: stress response
Amygdala: fear perception
Basal ganglia/ cerebellum: movement/ control
What CNS disorder can beta blockers be used to treat ?
Especially panic attacks
Target autonomic symptoms (ones you can't control) eg rapid heart beat, raised blood pressure)
What drug treats general anxiety disorder?
A benzodiazepine, full agonist at GABA A which causes sedation, useful for sedation before operations?
A benzodiazepine, partial agonist, known as a positive modulator of Cl channels of GABA A receptors? What about a partial inverse agonist?
Partial agonist: RO16-6028: positive modulator, increases inhibition therefore relaxes
Partial inverse agonist: RO15-4513: negative modulator, decreases inhibition therefore stimulates
A competitive antagonist of the GABA A receptor, which is good for reverse respiratory depression?
A benodiazpeine, An inverse agonist at the GABA A receptor?
What are Midozalam, bromazepam, clonazepam, diazepam and flunitrazepam all?
Strong agonists of the GABA A receptor, therefore they're all anxiolytics (anti-anxiety) they relax and sedate
Which benzodiazepines are hypnotics?
They're used to treat insomnia
What do all benzodiazepines end in?
Eg Midozalam, temazopam, diazepam
2 Keto drugs: ____ half life
3 hydroxy and triazolo drugs:_____ half life
2 keto drugs: long half life
3- hydroxy and Triazolo drugs: short half life
If a patient is prescribe a benzodiazepine, why shouldn't they drink alcohol?
Alcohol is ALSO a CNS depressant
Therefore they would interact
2 CNS depressants= too much inhibiton= can result in a COMA
Remember benzodiazepines are ANXIOLYTICS, not antipsychotics!!
People can become physically dependent on them, therefore you should "taper off" dose when coming off them
What does an EEG record?
Records activity of populations of neurone in the brain, records brainwaves. Uses electrodes recording on scalp. Detects electrical activity produced when afferent axons synapse and release glutamate.
How do we coordinate between rem and non rem sleep?
Cholinergic neurones increase their firing rate to start off phases of REM sleep.
Nor adrenaline neurones increase their firing rate when non REM phase starts. These two neurones work together.
We also have REM on and REM off cells
What could be used as a cure for jet lag to get body clock back on track?
Melatonin, derived from 5HT
It has it's own circadian rhythm
What three substances regulate your body clock and help your sleep?
What is narcolepsy?
A disorder where people are unable to regulate their sleep/ wake cycles
What scale is used to assess if somebody has a sleeping disorder or not?
Epworth sleepiness scale
Scores over 12= sleeping disorder
Examples of long acting benzodiazepines used as hypnotics to treat insomnia?
Long acting: NITRAZEPAM
These give rise to a "hangover effect" where you still feel drowsy the next day as they act all night to KEEP you asleep
Examples of short acting benzodiazepines used as hypnotics to treat insomnia?
Short acting: LOPRAZELAM, TEMAZEPAM
May not be as effective as long acting ones at keeping you asleep all night long
Which drug, is a very strong agonist at GABA A receptors, which make you fall unconscious and therefore use as a daterape drug?
Rohypnol (flunitrazepam) causes loss of memory.
Examples of NON benzodiazepine hypnotics?
These still bind to GABA A receptors
These only have a short duration of action. Only help you get off to sleep. Less likely to cause rebound insomnia.
What is the herbal remedy used to treat insomnia?
Acts on GABA, 5HT and adenosine receptors
You need to know not to take herbal remedies and a prescribed drug for the same problem, can result in too much sedation.
Which is more sensitive to changes bought about by antidepressants; the HAM-D scale or the MADRS scale?
Both scales are used for assessing severity of depression in people who already have been diagnosed with depression.
What is electroconvulsive therapy?
Electrodes on head induces a therapeutic clonic seizure
This is to try and jump start the brain, and get neurotransmitters flowing, to make brain more active
Used to try and cure depression
MAO A and MAO B, which is extra neuronal? Which is most common?
MAO B is extra neuronal and more common.
But MAO B does not degrade 5HT and N.A, therefore is not a antidepressant target!
Which MAO do antidepressants target? Why?
This is because it's more specific to 5HT and noradrenaline
What was the first drug to develop MAO inhibitory activity?
Hydrazines are a class of MAO inhibitors. What properties do they have?
They're irreversible and non selective (so target both MAO A&B)
They're non- competitive inhibitors
Examples of Hydrazines?
CYCLOPROPYLAMINES are a class of MAO inhibitors.what properties do they have? What's an example?
They're irreversible and non selective
An example is TRANYLCYPRAMINE
Acetylenic propargylamines are a type of MAO inhibitor. They are irreversible. They are selective to either MAO-A or B.
Mao-A selective; Clorgyline
Mao-B selective; pargyline, deprenyl (these are useless)
Look out for ~gyline!
What are the side effects of MAOIs?
Hypotension (low blood pressure)
Atropine- like side effects
What could potentially interact with antidepressants?
Things that decrease nerve impulse action and therefore have opposite effects to MAOIs
Eg barbiturates, Reserpine, alcohol, TCIs
With the tyramine cheese reaction / hypertensive crisis, what MAOIs are problematic?
Non selective MAOIs
Selective MAO-A Is
Results in large displacement of Nor adrenaline
Leads to elevated blood pressure and pulse rate
What is an example of a MAOI that won't trigger the cheese reaction if tyramine is eaten?
This is because it's a reversible MAO- A selective inhibitor.
Reversible means it will unbind from MAO if N.A levels get too high, so that N.A can then be broken down
Why have MAOIs declined in use?
Due to the Tyramine risk!
Risk of tyramine cheese reaction every time tyramine eaten in diet
Interest in developing selective and reversible MAOIs
What are the two main structural divisions of TCAs?
Dibenzazepines: two R groups that are different with each TCA
Dibenzcyclcoheptanes; one R group that is different with each TCA
Tricyclic antidepressant examples?
Chlorpromazine (also used to calm down psychotics)
Amozapine, Dosulepin, Doxepin, Trimipramine,
How do TCAs cause their side effects?
Through blocking neurotransmitter receptors, eg the muscarinic ACETYLCHOLINE receptor, histamine receptor and 5HT receptor. This does not contribute to the TCAs effect, but just causes side effects.
TCAs normally act by blocking reuptake of certain Neurotransmitters (5HT, NA)
What are atropine like side effects?
These are anticholinergic side effects
TCAs and MAOIs cause these
These effects are especially strong in amitryptyline
What will TCAs cause in non depressed patients?
Cause sedation and confusion
These also will occur in depressed patients in the first few days of treatment, therefore have to warn patients they will feel worse before they feel better!!
What are TCAs particularly likely to interact with/ cause side effects with?
Hypotensives (as TCAs act opposite to these)
(you'd never give a patient a TCA and a monoamine neurotrasmitter, as synaptic activity would be increased way too much!!)
TCAs: examples of selective 5HT reuptake inhibitors?
Sertraline , fluoxetine
These are selective to serotonin only
These are therefore SSRIs!!!
TCAs: example of NA- selective reuptake inhibitor?
TCAs can be selective because neurotransmitters have different uptake transporters!
How does reserpine worsen depression?
It blocks the VMAT transporter, which transports neurotransmitters into vesicles
Depletes levels of 5HT, NA and dopamine as they won't be in vesicles and therefore won't diffuse across the synaptic cleft
Methyl dopa and methyl-p-tyrosine also worsen depression by inhibiting NA synthesis
Are amphetamine, L DOPA and cocaine antidepressant?
Just stimulate/ increase alertness
SSRIS are selective to 5HT over Noradrenaline uptake. This makes them less likely to cause ______ side effects, compared to TCAs. Also they're less likely to cause _____ reactions in contrast to MAOIs.
Anticholinergic side effects
Tyramine Cheese reactions
TCAs are more effective at treating _____ depression than SSRIs
But SSRIs have a better _____ profile.
Side effects profile
It is suggested that ___effects is more effective than __ effects in antidepressive activity
5HT more effective than Nor adrenaline
This is because 5HT has an emotional component
This is why SSRIs only target 5-HT, they block 5HT reuptake ONLY
Examples of SSRIs?
Remember SSRIs are 5Ht selective, smaller ____ for 5HT in relation to NA, this means theyre more potent for the 5HT transporter than the NA transporter.
This means a lower conc of the SSRIs are needed to inhibit the 5HT transporters in comparison to the 5HT transporters
What is the name of the autoreceptor that suppresses firing rate of 5HT?
What do the 5HT2A and 2C receptors cause?
Cause an individual to feel self punishment and fear.
5HT2A causes anxiety
5HT2C causes fear and panic
It's the final downregulation of post synaptic 5HT receptors, especially ________ that ultimately results in a person with depression feeling better after a few weeks of treatment!
5HT2A and 2C
These become less sensitive to 5HT, because the 5Ht levels have risen and repeatedly acted on them causing them to desensitise, this results in them not being able to produce feelings of fear and anxiety any more.
So we can see that it's not only the increase in 5HT causing increased stimulation, it's not this that cures the depression. It's more likely.....
To be the 2A and 2C 5HT receptors becoming less sensitive to 5HT after a few weeks of treatment, which decreases anxiety and fear, as less 5HT responsiveness which results in less anxiety and fear/panic that is the usual effect of these receptors being activated!
This is WHY antidepressants take a few weeks to start working,
What are the effects of the 5HT1A receptor?
Autoreceptor that Suppresses firing rate of 5HT
Less 5 HT leads to less anxiety and fear and therefore less depression
Symptoms without it: helplessness, suicide
Antidepressants act to INCREASE its action
Older TCAs are _______
This means they're dangerous in overdose.
They can impair memory
Antidepressants need to be continued for _____ months after clinical recovery.
For four months.
Patients should be advised to continue treatment even if they are feeling well.
How long does a manic episode last for?
To be classed as one, it lasts for at least 1 week
What do mood stabilising drugs do? Examples?
Reduce BOTH the manic and depressive phases of bipolar.
If they're given in acute attacks, they're effective ONLY at reducing mania (ie if they're only given in manic attacks).
LITHIUM is the most common mood stabiliser used.
Antiepileptic drugs eg CARBAMAZEPINE can also be used.
These both will only reduce mania in acute episodes, but reduce both mania and depression
How long does it take for the treatment of lithium and Antiepileptics to kick in?
It takes 3-4 weeks
Lithium is mainly confined to prophylactic control of manic depressive illness. What does this mean?
Ie it's used as a prevention of getting a mood swing.
Other drugs (antipsychotics) are equally effective as lithium at treating acute mania, they act more quickly and are safer. This is why they're preferred to lithium, and lithium use should therefore only be for prevention.
What is lithiums therapeutic window?
0.4mmol/L to 1.0 mmol/ L
Above 1.5 mmol/L= potentially fatal
(in normal people without bipolar, 1mmol/L of lithium has no appreciable psychotropic effects)
Lithium has quite a bad side effect profile.
Some side effects include?
Polydipsia (excessive thirst)
Polyuria (excessive urination)
Aggravates skin disorders
Loss of appetite
What are the chronic side effects of lithium use (long lasting)?
Thyroid goitre (swollen thyroid gland, could be related to the weight gain)
What, at the moment, is the primary drug of choice to treat bipolar? What are gaining favour for treatment?
Primary drug: Lithium
But carbamazepine, valproate and gabapentin are all gaining favour for treatment of mania, due to better side effect profile and safety profile.
What branch of mental illness is schizophrenia?
It is nonorganic, and is a branch of DEMENTIA PRAECOX
What are characteristic positive symptoms of schizophrenia?
Abnormality, distortion, EXAGGERATION
These are psychotic behaviours, they make people loose touch with reality
Hallucinations, delusions, abnormal behaviour like aggression, and abnormal language wild chains of thought etc. they're seen as positive as they're extra additions onto normal behaviour.
What are characteristic negative feelings of schizophrenia?
Opposite to positive symptoms
Feelings of LOSS and lacks of feelings!
Lack of motivation (avolition)
Anhedonia (lack of feelings of pleasure)
Affective blunting (no emotional expression)
Poverty of speech (the person says the bare minimum)
Antipsychotic drugs treat schizophrenia, which are in the Typical (first generation) category?
Phenothiazines, thioxanthines, Butyrophenones
Atypical antipsychotic drugs (second generation) classes?
Dibenzodiazepines, Benzamides, Benzisoxazole
Chlorpromazine is a phenothiazine of the Typical antipsychotics group. Is has success in treating schizophrenic patients and calming them down.
How is its action bought about?
Through antagonism of dopamine, stops dopamine having a stimulatory effect and therefore calms the patient down.
What effects do antipsychotics have on the CNS?
Drowsiness and sedation
Acute dystonias: twisting if muscle, abnormal posture
EPS: extrapyrimidal symptoms; involuntary repetitive movements
Tardive dyskinesia (slow involuntary repetitive movements)
What is neuroleptic malignant syndrome?
A life threatening neurological disorder, most often caused by an adverse reaction to neuroleptics (antipsychotic) drugs
What are neuroleptics?
Used to treat schizophrenic patients and calm them down during a manic phase
For antipsychotics to have a therapeutic effect, how much potency do they need to have on dopamine receptors?
Need to have have about 80 % occupancy of D2 receptors
Affects on the _________ dopamine pathways are believed to correlate with antipsychotic effects (ie give the antipsychotic effects, dopamine antagonism in this pathway makes the patient better).
Affects on the _________ dopamine pathway are responsible for the unwanted motor symptoms, such as EPS.
Mesolimbic/ mesocortical pathway= antipsychotic effects
Nigrostriatal pathway= unwanted motor effects
What do the corticospinal and Rubrspinal (spanning from the midbrain) innervate?
These two tracts are lateral, and innervate the distal musculature, which are the extremities such as fingers and toes. They're concerned with very discrete voluntary and skilled movement such as writing.
Where does the rubro spinal tract originate from?
The red nucleus of the midbrain. Relatively small neurones connect the midbrain to the spinal tract.
What does the cortico spinal tract connect?
Longest neurones in your body, these connect your motor cortex of the brain (top of it) all the way down to your spinal tract.
Lateral and anterior cortico spinal tract
to do with discrete voluntary skilled movement
Axons span down through the brain stem through midbrain and medulla
What hemisphere of the brain controls the right Side of your body?
Remember opposite sides of brain controls either side of the body
Cortico spinal tract influences this
What is pyramidal decussation?
Some of the Pyramidal fibres leave the pyramids in bundles, and cross over eachother, decussation is the crossing over of neurones.
What do the ventro-medial motor pathways innervate?
These are the vestibulo, reticulo,and tectospinal tracts.
They innervate the trunk and head muscles (axial) and muscles closest to the midline of the body (proximal). This tract innervates the larger muscles of the body!! Not involved with finer muscles like the cortico and Rubrospinal tracts...
Where does the vestibulo spinal tract originate from and where does it terminate? What does it control?
Originates from the medulla of the brain stem, terminates at the spinal tract, it's involved with posture and head stabilisation. Medial tract supports the head, lateral tract maintains posture and stability if knocked off balance.
Where does the tectospinal tract stretch from an too, and what does it coordinate?
Originates in the superior colliculus of the midbrain, then travels through the medulla of the brain stem and terminates at the spinal chord.
It coordinates head and eye movements in response to visual stimuli.
Responsible for motor impulses that arise on one side of the midbrain to innervate muscles on the opposite side of the body.
The reticulo spinal tract consists of two tracts. These are the medial and lateral reticulo spinal tracts. Where do they both originate from?
Medial: pontine reticular formation of the cerebellum (not on brainstem, but crosses through the brain stem)
Lateral : medullary reticular formation (medullary is part of the brain stem)
What are the lateral pathways of descending motor control?
The cortico spinal tract
The rubrospinal tract
Both control proximal and distal muscles (fingers and toes)
And responsible for most voluntary movements of the arms and legs
What are the (ventro) medial pathways of descending motor control?
The vestibulospinal tracts
The reticulospinal tracts
The tectospinal tract
Control the axial muscles
Responsible for posture, balance, and some control of axial and proximal muscles
The substantia nigra is split into two. What are these two called?
The substantia nigra pars reticula.
And the substantia nigra compacta.
What two areas together make up the striatum?
The Putamen and the caudate nucleus
The striatum is the main receiving area of the basal ganglia
It receives info from the whole cortex
What is the globs pallidus of the basal ganglia split into?
Internal and external segments
GPi and GPe
What are the 3 parts of the cortex?
Motor. Prefrontal. And sensory
These are all interconnected with EACHOTHER
Motor cortex: tells muscles to actually move
Prefrontal: functional in decision making, it assesses a situation, thinks about risks involved and tells you whether to do something.
Sensory: receives sensory input eg noises
Prefrontal can take info from the sensory cortex, process it, then tells the motor cortex what to do.
How does the prefrontal cortex actually tell you to move?
Prefrontal cortex puts a lot of information into the basal ganglia. This then loops to the thalamus which stimulates your motor cortex. Basal ganglia also stimulates brainstem which sends info to your spinal chord.
With involuntary movements, the sensory cortex interconnects straight with the motor cortex, and bypasses the prefrontal decision making cortex.
The direct and indirect pathways through the basal ganglia are used to regulate the excitement of the cortex, which pathway
results in this excitement?
The DIRECT pathway results in excitement of the cortex, through less inhibition of the thalamus .
The INDIRECT pathway results in less excitement of the cortex, through increased inhibition of the thalamus.
What provides a modulatory influence on the direct and indirect pathways of the basal ganglia?
Dopamine modulated both
The nigrostriatal dopamine pathway modulates both
The direct pathway is activated by D1 receptors
The indirect pathway is activated by D2 receptors
Modulation by SNc (substantia nigra compacta) balances the pathways
What do D1 and D2 (seperate answers) receptors in the Basal Ganglia result in in terms of the cortex?
D1 result in increased cortex stimulation, through stimulating the direct pathway which leads to less inhibition of the thalamus.
D2 also result in increased cortex stimulation, through inhibition of the indirect pathway (which usually acts to decrease activation of the cortex)
This is how control of the excitement of the cortex comes about. As We only want it to be activated when dopamine binds to dopamine receptors.
The cortex is only activated when dopamine binds to D1 and D2 receptors!...
When these receptors aren't activated by dopamine, the indirect pathway results in deactivation of the cortex, whilst the direct pathway results in activation of the cortex. Therefore when dopamine is not bound to its receptors, there is no net effect on the cortex
Therefore, we can say that dopamine controls _____ (neurotransmitter) excitatory effects, and _______ inhibitory effects in the brain (on the _____).
Glutamate excitatory effects
GABAs inhibitory effects
On the cortex
What does the cerebellum act to do?
It does not initiate any movement
It contributes to coordination, precision and accurate timing
Acts to finely tune motor activity and tidy it up
What is Parkinsonism?
A drug induced form of Parkinson's, caused by neuroleptics and by MPTP, a drug of abuse, related to ecstasy and heroin.
What is it that degrades in Parkinson's?
The substantia nigra
The substantia nigra compacta is lost, therefore no dopaminergic regulation of the indirect and direct pathways of the basal ganglia. The modulatory part of the substantia nigra is lost (SNc) due to no dopamine
What leads to a loss of movement with Parkinson's?
Increased inhibition of the thalamus due to the direct pathway not being stimulated by D1 anymore and due to the indirect pathway not being inhibited by D2 any more. This switches off thalamo-cortical pathways. Less excitation of thalamus
Leads to loss of cortico-spinal output
Results in decreased movement and rigidity
What is Chorea? What's it a symptom of?
Involuntary jerking movements
Symptom of Huntingtons
What are the symptoms of Huntingtons?
Chorea (involuntary jerks)
Balance problems.foot fall (gait) problems
Swallowing and speech problems
What causes these involuntary movements in Huntingtons?
Caudate neurones degenerate
Ultimately results in less inhibiton of the thalamus...
Therefore this leads to more stimulation of the motor cortex which results in involuntary movements
How are Parkinson's and Huntingtons the opposite to EACHOTHER?
Huntingtons ultimately is cause by decreased inhibiton of thalamus which leads to increase stimulation of the motor cortex
Parkinson's ultimately is caused by increased inhibition of the thalamus which results in less stimulation of the motor cortex
What is ataxia and what is it a symptom of?
The lack of voluntary coordination of muscle movements,
It's a symptom of cerebellar dysfunction
With this disease we loose our fine motor control and coordination
Anything to do with pons/ pontine are to do with the.....
What part of the brain does alcohol effect?
effects the cerebellum
it effects balance and movement coordination: cerebellum involved in this.
Many patients with diseases in the __________ have abnormal eye movements
Huntingtons and Parkinson's are diseases of the basal ganglia
What area of the brain does epilepsy effect?