Lecture 8 - Neurobiology and Pharmacology of Schiz Flashcards Preview

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Flashcards in Lecture 8 - Neurobiology and Pharmacology of Schiz Deck (95)
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1

Outline Otto Loewi 1921 study on neurotransmitters in frog heart chambers

Isolated 2 hearts in bath solution liquid saline
1 each side connected by saline solution
Electrical impulse 1 heart cause it to best
2nd heart beats at same ear

2

What is the criteria of a neurotransmitter

Produced within a neuron
Found within a neuron
Neuron stimulated (depolarised) neuron must release the chemical
Chemical released acts on post synaptic receptor causing biological effect
After be inactivated. Through reputable or analyse stops activation
Chemical applied on post synaptic membrane same effect when released by neuron

3

What are the 4 classes of neurotransmitters

Amino acids

Biochemical amines

Peptides

Others

4

Why is glutamate a major excitatory neurotransmitter

Gets things done quickly
Multiple pathways use it
Abundant
Synthesised from glutamate in astrocytes
Released synaptic cleft
Removed synapse by glutamate transporters

5

Outline what pathways use glutamate

Cortical Association
Cortico-Thalamic
Cortico-Spinal
Basal Ganglia
Hippocampal
Cerebellar

6

Summary of the pathways in glutamate location and how it is released

Pathway from VTA substantia nigra going PFC. To struts thalamus to PFC

7

What happens presynaptically for glutamate

Stored vesicles released into extracellular space
Synaptic glutamate stimulate glutamate receptors both pre and post synaptic neurons
Before cleared by EAAT locates glial cells to begin cycle again

8

Outline presynaptic dopamine role

Transported to vesicles release contents increase Ca2+
Stimulate dopamine receptors both pre and post synaptic neurons
Before cleared DAT or metabolism
VTA projects PFC and substantia nigra

9

Outline modulatory dopaminergic neurons

Project dorsal striatum via substantia nigra, central striatum, pre frontal cortex via VTA
Thalamus reciprocal excitatory glutamate connections to striatum and PFC

10

Outline prefrontal cortical efferent and glutamate

Prefrontal cortical efferent excitatory glutamate neurons extent to striatum nucleus accumbens and VTA

Located number different regions

11

What are the subtypes are glutamate receptor

Different effects depending which receptor NT binding to

NMDA
AMPA and Kainate
Metabotropic

12

What are the 2 classes of glutamate receptors

Ionotropic

Metabotropic

13

Outline Ionotropic glutamate receptor

Receipts act really fast
Gateway
Vision, perception
Glutamate

14

Outline metabotropic receptors

Stimulate other molecules
In turn stimulate other molecules etc
Slower, tasting, pain
Dopamine

15

What is the role of a neurotransmitter

Enhance synthesis - increase rate being produced

Increase release

Block reuptake

Reduce metabolism

16

Outline role of a receptor

Mimic effect
Antagonist
Allosteric modulator

17

What does reduced function of NMDA glutamate receptors lead to according to glutamate Hypothesis

Reduced glutamate transmission

18

Outline Kim 1980 on glutamate Hypothesis

Reduced glutamate in cerebrospinal fluid in Schiz ppts

19

Outline role of PCP and Ketamine in Glutamate Hypothesis of Schiz

NMDA antagonists = block glutamate receptor
Produce positive and negative symptoms
Hallucinations, delusions, psychotic episodes
Depressive, lack of motivation

20

How do genes associate with the glutamate Hypothesis of Schiz

Genes associated increased risk Schiz
Influence function modulatory sites NMDA receptor or intracellular receptor interacting proteins
Link glutamate receptors signal transduction pathways

21

Outline an example of genes associated with glutamate in Schiz

Associated allergic variants of genes for neuregulin 1
Influence expression NMDA receptors through activation of Erb4 receptors and GRM3
Encodes the mGlu3 subtype of metabotropic glutamate receptors

22

What do post mortem studies tell us of glutamate Hypothesis of Schiz

Show changes in glutamate receptor binding transcription and subunit protein expression
In pre frontal cortex thalamus and hippocampus Schiz
Down regulated levels

23

Examples of findings from post mortem studies on glutamate Hypothesis of Schiz

Decreases in NR1 subunits of NMDA receptor in hippocampus and frontal cortical areas

24

What do glutamate neurons regulate according to the glutamate Hypothesis

Function of other neurons
Dopamine - target of antipsychotic drugs.
Glutamate acts as break on dopamine:
Loss receptors remove break increase dopamine release
Causing dopamine hyperactivity by reduced glutamate function

25

How is the bursting of dopamine neurons implicates in glutamate Hypothesis

Integral component of response to environmental stimuli
Depending on activation of NMDA receptors these neurons

26

How are D2 receptors linked to glutamate Hypothesis

Localised presynaptically in glutamate terminals and work inhibit release glutamate
Reduced D2 receptor function produces modest increases glutamate release

27

What pathways are involved in the glutamate Hypothesis

From VTA to PFC (glutaminergic pathways)
VTA to nucleus accumbens (Mesolimbic dopamine pathway)
Under active and kept in check by glutaminergic pathway

28

How does the glutamate hypothesis explain the positive symptoms of Schiz

Glutamate System hypoactivate
Consequence
Dopamine System overactive

29

What are the consequences of glutaminergic hypofunction

Reduced brain function
Negative cognitive and affective symptoms

30

What is the dopamine hypothesis of Schiz

Overactivity of dopaminergic synapses likely Mesolimbic pathway coming from VTA