synaptic excitation and inhibition:epilepsy

Question 1

what is the brain’s major excitatory neurotransmitter?

Answer 1

50-80% of nerons are glutamatergic - glutamate

Question 2

what are the two groups of glutamate receptors?

Answer 2

1. ionotropic = fast synaptic transmission
   
   1. NMDA , AMPA, Kainate
   2. gated Na+ and Ca2+ channels
2. Metabotropic = slow syaptic transmitsion

Question 3

what Are the two types of GABA receptor ?

Answer 3

GABA A = post synaptic, ionotropic ligand-gated, linked to Cl - channels

GABA B= pre-synaptic autoreceptors, metabotropic, linked to K+ channels

Question 4

What type of nerotransmitter is GABA?

Answer 4

it is a major inhibitory neurotransmitter

Question 5

do neurons fire in sync? or do they stagger?

Answer 5

they do not syncronize, they all send signals at different rates

Question 6

describe the mechansim of excitation and inhibition

Answer 6

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

Question 7

How do most anti-convulsants work?

Answer 7

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

Question 8

Describe how gene mutations could effect the excitabiltiy of neurons

Answer 8

Question 9

how could damage to one excitatory neuron effect the activity of another neuron?

Answer 9

unbalanced excitation/inhibition = seizures

Question 10

damage to glial cells can lead to what?

Answer 10

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

Question 11

what is epilepsy characterized by?

Answer 11

by abnormal and excessive firing/synchronizaiton of a population of neurons leading to recurrent seizures

Question 12

describe how neurons firing in normal brain function differs from neuron firing in a seizure

Answer 12

in an epileptic brain

• sudden abnormal hyper-synchronous electrical neuronal activity that temporarily interrupts normal brain function

Question 13

describe focal vs. generalized onset

Answer 13

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 $

Question 14

what tool do you use to diagnose a seizure?

Answer 14

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

Question 15

what would you see on an EEG in the event of a seizure?

Answer 15

Question 16

when is epilepsy normally diagnosed?

Answer 16

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

Question 17

what is the difference between generalized and focal seizures upon EEG?

Answer 17

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

Question 18

what are pseudo seizures?

Answer 18

psychogenic non-epileptic seizures

• often manifestations of psychiatric disturbance ( patient may or may not be aware)

distinguish psychogenic from real seizure with an EEG

Question 19

what sort of anti-peileptic drugs do we use?

Answer 19

• phenytoin
• carbamazepine
• valproate
• lamotrigine
• gabapentin

Question 20

what drugs do we do to terminate acute seizures?

Answer 20

lorazepam and barbiturates

“flood brain with GABA”

Question 21

what effect do epileptic seizures have on the brain?

Answer 21

• 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)

Question 22

what is status epilepticus?

Answer 22

a severe, continous seizure without recovery - normal seizure self-termination mechanisms fail - medical emergency as significant morbitiy can result -

Question 23

what can status epilepticus cause?

Answer 23

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

Question 24

What would we see on EEG in the even to of a focal seizure?

Answer 24

starts in one or more areas and spreads to all areas