journal club stuff Flashcards by Sylvie Wilson

overall glycine decarboxylase (GLDC)

effects in mice

causes neural tube defects

cuases features of non-ketotic hyperglycinemia

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which mechanism is linked to human neural tube defects (NTDs)

aberrant folate metabolism

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effect of Glycine decarboxylase (GLDC) on folate metabolism

provides the carbon units

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what do GLDC mutations cause

non-ketonic hyperglycinemia

linked to NTDs

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GLDC

glycine decarboxylase

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NTD

neural tube defect

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mice with reduced GLDC activity

develop (non-ketotic hyperglycinemia) NKH
NTDs
altered folate profiles

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administration of formate to mice with reduced GLDC activity

reverses effects of NKH and NTD by providing an alternative source of carbon units and normalising folate profile

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mitochondrial folate metabolsim is important in

neural tube development

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what are drugs that target GABA signalling used for

anti-anxiety
anti-convulsants
analgesic
anaesthetics
muscle relaxants

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GABAa receptors

pentometric
ligand-gated ion channels
diverse subunit composition mixture

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different subunit compositions of GABAs receptor s

confer different receptor properties

give different physiological effects

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different physiological effects of GABAa receptors

drugs have different binding affinities for GABAa receptors

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GABAa binding sites

2 orthosteric binding sites
1 allosteric binding/modulatory site

also a possible alternative site

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muscimol

selective agonist for GABAa receptor

binds to the orthosteric site

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fluni-traz-epam

benzodiazepine

binds to modulatory/allosteric site

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allosteric modulator

substance which directly influences the effects of a receptor agonist or inverse agonist at its receptor target

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where do allosteric modulators bind

a site distinct from the orthosteric site where a receptor agonist would normally bind

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effect of allosteric modulator on structure of receptor

usually induce a conformational change within the protein strucutre

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EC10

concentration of an agonist that produces 10% of the maximal possible effect of that agonist

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docking binding energy

a measure of how well the ligand binds the receptor binding site

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more negative docking binding energy

the better the ligand ‘fits’ the receptor binding site

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DCUK-OEt

subunit-selective positive allosteric modulator at the GABAa receptor

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where does DCUK-OEt bind to GABAa receptors

appears to act at a site distinct from the benzodiaepine site

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example of a monosynaptic pathway

Schaffer Collateral Commissural pathway

links CA3 cells to CA1 cells in hippocampus monosynaptic pathway neurotransmitter = glutamate

when action potential arrives via CA3 cells...

voltage gated Ca2+ entry triggers Glu release at synapses EPSP induced in CA1 cells

measurements taken in CA1 cells

EPSP recorded with appropriately placed extracellular electrode

how are action potentials evoked in CA3 axons

standard stimulating electrode

how is pre-synaptic Ca2+ measured

using a Ca2+ sensitive fluorescent dye selectively loaded into axons by a local injection

aim of measuring Ca2+ in pre-synaptic neuron

measure Ca2+ transient produced by pre-synaptic action potential relate this to the post-synaptic response measured electrically

how is the fluorescence from Ca2+ captured

with a photodetector

higher probability of release means that

the electrical response is bigger when Ca2+ entry is promoted

effect of width of action potential

wider AP is better at turning on V.G. Ca2+ channels and leaving them open longer more Ca2+ entry

how do you manipulate pre-synaptic action potential width

use a drug 4AP which blocks some of the K+ channels involved in AP repolarisatoin

effect of adenosine on Ca2+ entry

acts as an agonist of Gi/o signalling | depresses Ca2+ entry

when was LTP discovered

late 1970s

what is LTP a good model of

how the brain forms and stores new memories

why would a one-trial inhibitory avoidance learning procedure be used

to show that learning can induce changes to synaptic strength

IA learning

inhibitory avoidance learning

effect of IA learning on Glu receptors

induces phosphorylation of specific resideus of GluR1 and GluR2 subunits suggests learning is inducing changes to post-synaptic receptors

what leads us to believe that subpopulations of synpases are functionally altered following learning

multi-electrode recording reveals that only some recording locations are significantly changed by IA-learning

what do neuro-imaging techniques rely on

the fact that more active areas of the brain require more energy so they need more oxygen and glucose

3 types of neuro-imaging

Arterial spin labelling (ASL) Blood Oxygen Level Dependent (BOLD) Magento-encephal-ography (MEG)

features of Arterial spin labelling (ASL)

fMRI technique doesnt require contrast agent non-invasive

method of arterial spin labelling (ASL)

modify the magnetization of arterial blood measure the delivery of the magnetically tagged blood to target tissues

when is an image acquired in ASL

when the magnetically tagged blood has reached the target tissue

blood oxygen level dependent (BOLD) fMRI

assesses changes in oxygenation in the blood

method of blood oxygen level dependent (BOLD) fMRI

detects differences in magnetic properties of oxyhaemoglobin vs deoxyhaemaglobin

why does magentoencephalography (MEG) work in the brain

synchronised neuronal currents induce weak magnetic fields

what do MEG and EEG signals derive from

the net effect of ionic currents flowing in the dendrites of neurons during synaptic transmission

Maxwell's equations

any electrical current will induce a magnetic field

how many active neurons are needed to generate a detectable signal

50,000

ASL noise compared to BOLD noise

ASL noise is a lot whiter than BOLD signals

main feature of ASL

does not require contrast agents

changes in perfusion seen in ASL

more localised to parenchyma

changes in perfusion seen in BOLD fMRI

changes are tied to veins and venules

time to collect ASL image

takes longer than BOLD

time to collect BOLD images

can get images in less tahan 500 msec

slices in ASL

fewer at a time with ASL | slices are thicker

challenges with controlling neuroimaging studies in humans

stable baseline measurements individual differences specificity of measurements resolution

potential medical benefits of LSD

reduce anxiety, pain, depression and anorexia nervousa

ethical implication of LSD study

could potentially cause harm not hypothesis driven effects variable and not clearly documented

journal club stuff Flashcards

(63 cards)