LG 3.10 PHYS - Mechanisms of Seizures Flashcards
What happens to the membrane potential during the Interictal stage of a seizure? What does this lead to in the Tonic Phase?
During the Interictal phase, membrane potential begins to increase. This leads to a depolarized state where multiple action potentials can be fired.
In the Tonic phase the membrane is still depolarized and there are multiple action potentials one on top of another.
What is another name for a focal seizure? What is a focal seizure? (start from, preceded by, can lead to?).
Partial seizure.
Start from small group of localized neurons.
Preceded by aura (sense of fear, rising feeling in abdomen, specific odor).
Focal seizures can spread and generalize (secondarily generalize).
What are the two types of partial seizures? How do they differ?
Simple partial: no alteration in consciousness.
Complex partial: alteration in consciousness.
How does a generalized seizure differ from a partial seizure?
No aura.
Involve both hemispheres from onset.
Seizure is an imbalance between what?
Excitatory (EPSP) and inhibitory (IPSP) synapses.
What are two main types of inhibitory synaptic channels? Why are they inhibitory (what are they doing chemically)?
GABA-B - inhibit Ca+ into cell, cause K+ to leave cell.
GABA-A/Glycine: allow Cl- into cell.
What are two types of pathways that can cause an inhibitory signal on a neuron?
Feed-forward inhibition: an inhibitory neuron gets excited and that excitement sends an inhibitory signal to the next neuron.
Feeback (Recurrent) inhibition: a neuron sending out a signal activates an inhibitory neuron upon itself to limit how much action potential it releases.
How are neurons controlled (what signals)? Due to this control, what can a seizure be considered?
Control:
Excitability of individual neurons.
Local inhibition of neurons.
Seizure can be considered the loss of control of neural circuits.
What three ways can control of neural circuits be lost?
Increased excitability of neurons.
Loss of local inhibition.
Spread of excitation.
Neuron excitability depends on the neurons ability to get to threshold in order to release an action potential. Name a few of the intrinsic and extrinsic mechanisms affecting excitability.
Intrinsic: Conductance of ion channels. Response of membrane receptors. Cytoplasmic buffering.
Extrinsic: Neurotransmitter presence at synapses, Temporal and spatial properties of synaptic and non-synaptic input. Support cells in ECF.
What is unique about central neurons? Describe how this is made possible?
Central neurons can have repetitive firing of action potentials.
The Na+ current that makes up the action potential in central neurons, has a higher threshold for activation.
Na+ current does not inactivate at resting potential, inactivation occurs at a significantly depolarized level => sustained depolarization can produce repeated action potentials.
Fast, outward K+ current allows for rapid repolarization of the membrane.
Ca++ currents and persistent Na+ currents can keep the cell depolarized to produce repetitive firing.
What can occur within glia cells that results in neuron excitability?
Glia cells absorb and release glutamate. They also absorb and modulate GABA.
A Ca+ surge in glia cells can lead to a large glutamate release, therefore affecting local neurons and causing seizure.
What affect could repetitive discharge from a group of neurons have on neuron excitability?
Increase in K+ outside the cells.
Limits K+ exit from cells.
Depolarizes neighboring cells.
Accumulation of Ca++ in nerve terminals leads to furthery synaptic release (presynaptic).
Ca++ entry through NMDA glutamate channels (postsynaptic).
The mechanism of a partial seizure begins with the focused, localized, region of the brain where activity starts. Neurons in this focus display a paroxsysmal deploarizing shift (PDS). What is this shift? What does this shift trigger? Which channels are in charge of causing this PDS?
20-40mV positive shift in membrane potential lasting 50-200 msec.
The shift triggers a train of action potentials at the peak of the shift.
Activation of glutamate AMPA/NMDA and voltage-gated Ca++ channels causing this PDS.
This PDS and action potentials involved are followed by a state of depolarization. What is the name of this state, what does it limit? Which channels are in charge of causing this?
The afterhyperpolarization (AHP). Limits the duration of the depolarizing shift.
Mediated by: voltage-dependent K+ channels, GABA-mediated Cl- and K+ conductances.
The PDS can be considered to be a gross exaggeration of what?
The basic cortical circuit: excitation followed by inhibition.
Neurons in the seizure focus are firing action potentials at the same time at a high rate. What mechanisms synchronize this dance? How many neurons need to be affected in order to see clincal symptoms?
Input from subcortical neurons. Intrinsic mechanisms such as recurrent excitatory connections. Gap junctions, electrical field effects. Increased extracellular K+ concentration (role of glia cells in controlling extracellular K+ and glutamate).
No clinical symptoms if abnormal discharge is restricted to about 1000 neurons in seizure focus.
Another mechanism for seizures can be the loss of local inhibition on neural circuits. Why is this thought to have such a big affects I mean seizures are massive events, some little inhibition can affect that? (hint: how do cortical inhibitory post synaptic potentials differ from inhibitory post synaptic potentials in spinal cord).
Cortical inhibitory post synaptic potentials are much larger and last 10-20x as long as the ones applied in the spinal cord.
What is the concept of an inhibitory surround regarding control of cortical circuits (draw this out)?
Inhibitory interneurons create the inhibitory surround.
Inhibitory surround restricts the center excitability and its spread.
During a seizure = lose inhibitory surround.
Regarding GABA what type of chemical would cause local spread of excitability? give an example.
Antagonizing GABA.
Penicillin can act as a weak GABA-A antagonist.
The breakdown of the inhibitory surround would have what affect on the AHP? What affect would this have on the neuron? What affect would this have on GABA, glutamate, Ca+ channels?
Breakdown of the inhibitory surround leads to reduction of the AHP.
With no AHP the neuron will display nearly continuous high-frequency firing.
AMPA/NMDA channels will become overactive, GABA release will stop, Ca+ conductance will be prolonged.
During recovery of a seizure what happens with GABA and what does this do to the continuous discharge?
GABA comes back intermittently.
The continous discharge stops. AMPA/NMDA channels become less active.
GABA release can be reduced by intense discharge. The neurons are still viable but they release less GABA.
How can a partial seizure spread? What is one example of this? (clinical observation).
Spread of activity through local connections.
The Jacksonian March is a great example of a partial seizure spreading its way down the motor cortex.
How can a partial seizure generalize? What structure could facilitate this type of spread? What features would this structure have?
Spread of activity by distant connections.
Thalamus (relay station).
Reciprocal connections, distributed connections, reversibility.
