what is the brain’s major excitatory neurotransmitter?
50-80% of nerons are glutamatergic - glutamate
what are the two groups of glutamate receptors?
- ionotropic = fast synaptic transmission
- NMDA , AMPA, Kainate
- gated Na+ and Ca2+ channels
- Metabotropic = slow syaptic transmitsion
what Are the two types of GABA receptor ?
GABA A = post synaptic, ionotropic ligand-gated, linked to Cl - channels
GABA B= pre-synaptic autoreceptors, metabotropic, linked to K+ channels
What type of nerotransmitter is GABA?
it is a major inhibitory neurotransmitter
do neurons fire in sync? or do they stagger?
they do not syncronize, they all send signals at different rates
describe the mechansim of excitation and inhibition
Excitation = to much
- ionic current - inward Na+ and Ca 2+
- neurotransmitters - glutamate and aspartate
Inhibition = too little
- ionic currents - inward Cl - , outward K+
- neurotransmitter GABA
How do most anti-convulsants work?
they work by promoting GABA function
- GABA antagonsits trigger seizures- glutamate antagonists stop seizures
Mutation of genes encoding voltage/ligand-gated channels cuase brain hyperexcitability
Describe how gene mutations could effect the excitabiltiy of neurons
how could damage to one excitatory neuron effect the activity of another neuron?
unbalanced excitation/inhibition = seizures
damage to glial cells can lead to what?
hyperexcitability - they play a role in the taking up the neurotransmitters when they are done, so damage to glial cells could lead to prolonged neurotransmitter time in the synapse = prolonged signal
what is epilepsy characterized by?
by abnormal and excessive firing/synchronizaiton of a population of neurons leading to recurrent seizures
describe how neurons firing in normal brain function differs from neuron firing in a seizure
in an epileptic brain
- sudden abnormal hyper-synchronous electrical neuronal activity that temporarily interrupts normal brain function
describe focal vs. generalized onset
focal = seizure orignates in one or more foci
- simple: patient remains conscious
- complex: patients loses consciousness
generalized onset = seizure beings simultaneiously in both hemispheres
- non-motor: brief loss of consciousness without loss of postural tone
- motor: tonic-clonic= convulsions/loss of consciouness $
what tool do you use to diagnose a seizure?
electroencephalogram ( EEG) - records weak electrical activity generated by the brain - it records the collective activity within the region -
ther is good resolution in time, but poor spatial resolution
what would you see on an EEG in the event of a seizure?
when is epilepsy normally diagnosed?
between seizures - transient abnormalities/discharges
like spikes and sharp waves, as well as slowing of the brain waves which is not consistant with behavioural state example in picture shown
what is the difference between generalized and focal seizures upon EEG?
generalized = begins simultaneously in both hemispheres
focal = starts in one or more foci/locations in the brain and then spreads to the rest of the brain
what are pseudo seizures?
psychogenic non-epileptic seizures
- often manifestations of psychiatric disturbance ( patient may or may not be aware)
distinguish psychogenic from real seizure with an EEG
what sort of anti-peileptic drugs do we use?
- phenytoin
- carbamazepine
- valproate
- lamotrigine
- gabapentin
what drugs do we do to terminate acute seizures?
lorazepam and barbiturates
“flood brain with GABA”
what effect do epileptic seizures have on the brain?
- altered gene expression
- promotes neurogenesis
- remodelling of synapses
- cell death (potentially)
- gliosis- reactivity of glial cells
- angiogenesis, vascular remodelling
- inflammation
- more seizures (Gower’s hypothesis - seizures increase liklihood of another)
what is status epilepticus?
a severe, continous seizure without recovery - normal seizure self-termination mechanisms fail - medical emergency as significant morbitiy can result -
what can status epilepticus cause?
seizures cause prlonged opening of glutamate receptor channels - could result in swelling/rupture due to Na+ and H2O entry - necrosis
“toxic” buildup of intracellular Ca2+
decreased energy, disruption of intracellular organelle function
over-activation of Ca2+ activated proteases
activation of programmed cell death pathways
What would we see on EEG in the even to of a focal seizure?
starts in one or more areas and spreads to all areas