lecture 8 LOs Flashcards
what can high levels of glutamate do
lesion any brain nucleus
what is excitotoxicity
prolonged depolarization of neurons leading to eventual damage or death
what is necrosis
fast death characterized by lysis due to osmotic swelling
what is apoptosis or programmed necrosis
a slower death triggered by a series of biochemical events. lysis does not occur
how can apoptosis/programmed necrosis happen
by lower concentration and longer exposure time to glutamate, cell death takes several hours and depends on NMDA receptor activation
how can brain damage occur
brain ischemia (interruption of blood flow from stroke/heart attack etc)
when a brain ischemia occurs, how does it happen
massive glutamate release occurs in the affected area
abnormally high Ca2+ levels inside the neuron overloads the Ca2+ buffers so they cant compensate
extremely high Ca2+ levels activate certain enzymes that kill cells
what is GABA the primary transmitter for in the brain
inhibition
which neurons use GABA
all medium spiny neurons in the striatum and other nuclei in the basal ganglia
projection neurons intermixed with monoamine cell groups (DA and serotonin)
interneurons in the cerebral cortex, hippocampus, amygdala, and most other brain regions
what does GABA transmission do for brain function
filter for info coming into neurons
regulates different patterns of firing in cortex
reduced GABA activity promotes seizures
many brain circuits are set up as a series of inhibitory GABAergic connections
how is GABA synthesized
from glutamate by glutamate decarboxylase (GAD)
where is GABA synthesized
in GABA neurons
where does the vesicular GABA transporter (VGAT) move GABA to
vesicles
how is GABA removed from the synpatic celft
reuptake transporters GAT1 to GAT3
where can GAT1 be located
on presynaptic terminals
how is GABA metabolized
it is metabolized to glutamate and succinate by GABA aminotransferase (GABA-T)
in astrocytes how is glutamate converted to glutamine
by glutamine synthesis
glutamine can be released by ___, taken up by ___, converted back to ___, and used to remake ___
astrocytes
neurons
glutamate
GABA
GABA-A GABA receptor subtype
ionotropic
allows Cl- to move from outside to inside the cell, aka hyperpolarization
each GABA receptor consist of ___ subunits
five
various combinations of the four types (alpha, beta, gamma, delta)
GABA binding site agonist and competitive antaonist
agonist: muscimol
competitve antagonist: bicuculline