lecture 8 LOs

Question 1

what can high levels of glutamate do

Answer 1

lesion any brain nucleus

Question 2

what is excitotoxicity

Answer 2

prolonged depolarization of neurons leading to eventual damage or death

Question 3

what is necrosis

Answer 3

fast death characterized by lysis due to osmotic swelling

Question 4

what is apoptosis or programmed necrosis

Answer 4

a slower death triggered by a series of biochemical events. lysis does not occur

Question 5

how can apoptosis/programmed necrosis happen

Answer 5

by lower concentration and longer exposure time to glutamate, cell death takes several hours and depends on NMDA receptor activation

Question 6

how can brain damage occur

Answer 6

brain ischemia (interruption of blood flow from stroke/heart attack etc)

Question 7

when a brain ischemia occurs, how does it happen

Answer 7

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

Question 8

what is GABA the primary transmitter for in the brain

Answer 8

inhibition

Question 9

which neurons use GABA

Answer 9

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

Question 10

what does GABA transmission do for brain function

Answer 10

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

Question 11

how is GABA synthesized

Answer 11

from glutamate by glutamate decarboxylase (GAD)

Question 12

where is GABA synthesized

Answer 12

in GABA neurons

Question 13

where does the vesicular GABA transporter (VGAT) move GABA to

Answer 13

vesicles

Question 14

how is GABA removed from the synpatic celft

Answer 14

reuptake transporters GAT1 to GAT3

Question 15

where can GAT1 be located

Answer 15

on presynaptic terminals

Question 16

how is GABA metabolized

Answer 16

it is metabolized to glutamate and succinate by GABA aminotransferase (GABA-T)

Question 17

in astrocytes how is glutamate converted to glutamine

Answer 17

by glutamine synthesis

Question 18

glutamine can be released by ___, taken up by ___, converted back to ___, and used to remake ___

Answer 18

astrocytes
neurons
glutamate
GABA

Question 19

GABA-A GABA receptor subtype

Answer 19

ionotropic
allows Cl- to move from outside to inside the cell, aka hyperpolarization

Question 20

each GABA receptor consist of ___ subunits

Answer 20

five
various combinations of the four types (alpha, beta, gamma, delta)

Question 21

GABA binding site agonist and competitive antaonist

Answer 21

agonist: muscimol
competitve antagonist: bicuculline

Question 22

inside GABA channel pore non competitive antagonist

Answer 22

picrotoxin

Question 23

what do benzodiazepine (BDZ) and barbiturates do

Answer 23

bind to receptor sites distinct from GABA binding site
increase the potency of GABA to open receptor channel, does not open channel if GABA is not also bound
positive allosteric modulator

Question 24

example of benzodiazepine (BDZ)

Answer 24

diazepam (vallium)

Question 25

barbiturate example

Answer 25

phenobarbitol

Question 26

what does benzodiazepine only bind to

Answer 26

the gamma subunit (which most receptors have)

Question 27

neurosteroid binding site

Answer 27

some neurosteriods act like BDZ but bind to different part of the receptor

Question 28

what do inverse agonist or negative allosteric moculators do at the BDZ site

Answer 28

no affect itself, but attenuates the ability of GABA to open channel, promoting anxiety, arousal, seizures

Question 29

GABA-B receptors

Answer 29

metabotropic (G-proteins and second messenger) require two different subuits to assemble in the membrane and work properly

Question 30

what does activation of GABA-B receptor do

Answer 30

inhibitory effect on post synaptic cells by K+ channel opening and inhibiting CAMP formation

Question 31

where else can GABA-B reside and serve as

Answer 31

can reside presynaptically and serve as autoreceptors or heteroreceptors

Question 32

GABA-B agonist

Answer 32

baclofen, used as muscle relaxant, and experimental treatments for alcoholism

Question 33

GABA-B antagonist

Answer 33

saclofen, convulsant primarily used for research

Question 34

NTs that are catecholamines

Answer 34

dopamine, norepinephrine, and epinephrine

Question 35

where are NE and EPI released from

Answer 35

adrenal medulla

Question 36

what are the behavioural functions from DA and NE

Answer 36

motor (primarily DA) learning and memory attention motivation and emotion reward

Question 37

what diseases are linked to catecholamine transmission

Answer 37

parkinsons, schizophrenia, depression, ADHD, drug addiction

Question 38

what does catecholamine synthesis begin with

Answer 38

the amino acid tyrosine

Question 39

where are tyrosine hydroxylase (TH) and dopamine decarboxylase found

Answer 39

in neurons that make DA used as markers for DA neurons

Question 40

what do NE-synthesizing neurons have

Answer 40

dopamine beta-hydroxylase (DBH)

Question 41

what is activity of TH and catecholamine production regulated by

Answer 41

high catecholamine levels inhibit TH activity (neg feedback) rate of cell firing (increased firing during stress stimulates TH to accelerate catecholamine synthesis)

Question 42

what does L-Dopa do

Answer 42

terminals take up precursor and quickly transform it to DA/NE increases transmitter levels

Question 43

what does AMPT do

Answer 43

blocks TH, preventing synthesis induces sedation, depression, reduced blood pressure (systemic effect) effects can be reversed w L-Dopa

Question 44

what happens to DA/NE after synthesis

Answer 44

packaged into vesicles via vesicular monoamine transporter (VMAT)

Question 45

what does reserpine do

Answer 45

blocks VMAT, prevents DA/NE from being packaged (irreversible)

Question 46

if DA/NE are not protected in vesicles, what happens and what is the effect of that

Answer 46

they are broken down by enzymes in terminal and levels drop results in sedation and depression and systemic effects (reduced blood pressure and heart rate)

Question 47

what have reversible VMAT inhibitors been developed for

Answer 47

reducing uncontrolled movements associated w huntingtons disease

Question 48

what are catecholamines metabolized by

Answer 48

monoamine oxidase (MAO) and/or catechol-O-methyltransferase (COMT)

Question 49

what is the primary mechanism of clearing catecholamines

Answer 49

reuptake

Question 50

what is the main DA metabollite

Answer 50

HVA (homovanillic acid)

Question 51

what are NE metabolites in the brain

Answer 51

MHPG enter CSF and bloodstream, eliminated via urine

Question 52

what can levels of HVA compounds in CSF provide

Answer 52

rough indication of catecholamine activity

Question 53

MAO inhibitor

Answer 53

phenelzine, used to treat clinical depression

Question 54

COMT inibitors

Answer 54

tolcapone, enhances the effecitveness of L-DOPA in treating parkinsons