NS Flashcards
Structure of Na VGC
Consist of alpha and beta subunits
Alpha subunit consist of 4 domain and each domain contains S1-S6 (six segments) with each domain linked by an amino acid chain
Function of beta subunits in Na VGC
Fine tuning properties on channels - it helps channel inactivation to occur faster
Can the Na VGC inactivate on its own With only alpha subunits?
Yes, beta subunits accelerate channel inactivation
In the ball and chain model for Na VGCs, whereabouts is this chain in the channel?
The amino acid chain between domain III and IV
S4 domain of the Na VGC does what to activate channel
Move towards the EXtracellulat side of the membrane as it is positively charged
Size difference between Na and K VGC
Na VGC is 4x larger than K+ VGC
How do we inactivate S type K channels
Delete the first 20 aminoacid at N terminal
Function of AKC is to
Delay onset and frequency of AP to allow variability in AP pattern
When does AKC open and how
AKC opens during depolarisation phase and closes later in the same phase as MP increases.
It requires hyperpilarisation in order to be activated again hence often fire after repeated firing or after inhibitory neurones activation
AKC is coded by
Shaker B
Structure of K delayed channels
4 alpha subunits consisting of 1 domain each come together without any physical linkage
TTX blocks
Na VGCs
TEA blocks
K+ VGC
APV blocks
NMDA channels
What blocks both Na and K channels
Lidocaine
Where is the primary cortex located
In the precentral gyrus - area 4
What Cortex are responsible for planning movements
Supplementary and pre-motor cortex in area 6
What’s a basal ganglia
A functional unit in the brain that consist of a group of associated subcortical nuclei
What’s the function of BG
Integrates sensory and motor input from cortex and modulate response via the promotors cortex via ventrolateral thalamus
Also selects and initiate voluntary movement
Disorders of basal ganglia is associated with
The inability to suppress unwanted movements - often present with dyskinesia
df. Of dyskinesia
Unwanted uncoordinated involuntary movements
Diminished voluntary movement
Pathological cause of Parkinson’s
Degeneration of dopaminergic neurones in the Nigro-striatal pathway which leads to the overactivaion of the SNc/GPi thereby constantly inhibiting the ventrolateral thalamus
Does patient with Parkinson’s always have uncontrolled movement?
No, if they are doing things or moving, the disinhibition of thalamus is released and hence the motor signals will override the default control
The limbic region includes
Anything that is associated with emotion regulation
- hippocampus
- amygdala
- neocortex
- thalamus (ATN)
- hypothalamus (PVN)
- ant. Pit.
Why do we need emotion
To communicate better
Helps learning and memory retention by giving relavence to the memory
The ANS symptoms exhibited in anxiety patients is due to
Increase activity of the hypothalamus as it is the centre of ANS control
Disease / disorders of the Amgdala
Kluver-Bucy syndrome
- range of behavioural abnormalities mostly characterised by decease in fear and lack of emotions
Urbach-Wiethe disease
-natural degeneration of amgdala
-patients unable to recognise facial expression
-sometimes patients can get TLE
what part of brain is related to the sense of pleasure
The orbitofrontal cortex
Mesolithic pathway
Runs via the medial forebrain bundle Via the VTA (ventral tegmemtal area ) to the nucleus accumbens and limbic area n the midbrain
What is the amgdala associated with
Fear and aggression
Patients with PTSD shows increase activity in the amygdala. Apart from SSRIs, what other methods can we use to treat these patients (surgical procedure)
Deep brain stimulation or removal of the amygdala
Drugs for treating anxiety
- think calming
- BDZ, 5-HT1A partial agonist (Buspirone)
- SSRI, a AR antagonist (symptomatic relief
The use of BDZ along with ethanol and opioids put patient in risk of
Severe respiratory depression
Unconsciousness (excessive sedation)
And potentially coma snd death
What happens to the hypothalamus if patient has chronic depression
Volume (size) of hypothalamus decreases
But reversible with use of drug
How does psychotherapy helps with anxiety or depression
Alter neurotransmitters transmission
Alter neuronal circuitry via change in synaptic plasticity
Desensitisation/habituation if phobic anxiety
Structure of GABAa receptor
5subunits - ABAB-gamma
Channel pore allows Cl- influx
GABA binding site is between AB whilst BDZ allosteric binding site is at A-gamma
Is depression or mood or thought disorder
Depression is a mood disorder
Thought disorder is the disorder of the mind - hence refer to psychosis such as schizophrenia
Definition of anxiety
An inappropriate manefiststion of fear response to a stressor which can be present or absent
Drugs treatment for depression
- atypical depressing man invites SIRI for Tea
- atypical neuroleptic
- MAOI
- SSRI
- TCA
Phenelzine is what type or class of drug
Non selective MAOI that blocks breakdown of Monoamine in mitochondria
Increase intracrllulwr and intrasynaptic monoamine levels
TCA such as amitriptyline and imipramine MoA and s/e
They are dirty drugs
Mainly block reuptake of 5-HT and NA
But because they are dirty drugs - give sedative effect (H1R antagnism
Fluroxetine and paroxetine are what class of drugs
SSRIS
Visual input travel up which fibre to the cerebellum
Climbing fibre
Reserpine, an neuroleptic that is often used as an depressant/hypotensive agent works by
Blocking presynaptic Mg/ATP dependent transport of amines from being packaged into vesicles
-deplete NA levels
What is the basis of learning and memory
LTP - the modification of synaptic transmission and connection
Potentiarion of the cell requires
Strong activation of synapses and synchronised firing of neurones
NMDA is a ________________ receptor that only opens when _______?
NMDA is a coincidence receptor that only opens when postsynaptic membrane depolarises in response to presynaptic firing
Process of LTP
Glutamate release and bind to both AMPA and NMDA receptor. However NMDA is blocked due to Mg+. The AMPA opening allows Ca/Na influx and K+ efflux. Further depolarisation of membrane results in repel of the Mg which opens up NMDA, allowing further depolarisation. Increase [Ca] cause activation of CAMKII (which is activated by CA-CAM). This will Pi AMPA which increase Na conductance, further depolarising membrane. Also drives gene transcription of more AMPA for insertion - mediated by SNARE. Ca also trigger retrograde signals which further stimulate presynaptic membrane, enhance synapse via neurotrophin release( BDNF)
How does LTD occur
If Ca influx is slow, it will activate Ca dependent dephosphorylation cascade which results in decreased signalling in post synaptic membrane and hence decrease insertion of AMPA
Plaques is formed by aggregation of
APP (amyloid precursor protein) that is important in neuronal repair and growth
What are sutures
Immovable joints in the skull (fibrous joints)
The sutures have zig zag patterns, what do they do
For stabilisation of bones
Hard to dislocate
The only way to break is to crush the bone
3 sutures
Saggital
Coronal
Lambdoid (parieto-occipital)
Where is the Calvaria
Top of skull bone above orbital bone (eye socket)
Middle cranial fossa contains a big hole where the brain stem passes through, what is that called
Foramen magnum
Technically the skull is composed of which two main compartment
Skull and the mandible bone connected by sphenoid bone
What does the subarachnoid space contain
Blood vessels
CSF
Nerves
Arachnoid granulation where CSF drains into superior saggital sinuses (in between the two dura mater later
Why do we need delayed AP firing
1) distinguish info from one stimuli from another
2) to generate patterns that allows complex behaviour
3) to hold back excitatory response
- protective sense
- can cause seizure/epilepsy if over fire
Flumazenil is what type of drug
Competitive antagonist of BDZ
Short acting
Barbiturates and BDZ increases what properties of the GABA Channels
Both barbiturates and BDZ binds to the GABA channel at dif allosteric sites
Barbiturates increases the duration of channel opening whilst BDZ increase GABA affinity thereby affecting the FREQency of channel opening
Lorazepam is amnestic and usually used for what Tx
Hypnotic drug for sleeping
- short acting agents
TCA drugs MoA
Serotonin dopamine reuptake inhibitor but also inhibit receptors such as H1R, mAChR causing serious S/E
SSRI MoA
Block SERT (5HT reuptake) More selective
UMN lesion results in
Movement deficit (not quite muscles)
Muscle wasting due to lack of use/disuse
Hypertonicity in muscles (spasticity)
Positive banbinski sign (abnormal > 1 yr)
Banbinski sign only exist normally in healthy babies under 1yr
Why is that
Corticospinal cord not fully developed so reflex will overpower the motor control
LMN lesion will cause
Individual/groups of muscles tonne affected
Pronounced Muscle wasting/atrophy
Flaccid/hypotonic muscles
Levetiracetam MoA
Block SV2A on vesicular membrane to inhibit release of excitatory NTR
Anticonvulsant
