CH4 Flashcards by Hanna Song

Behavioural measures are crucial for understanding the ________ basis of behaviour, and drug-induced changes in that behaviour. Developing ______ _____ of psychiatric disorders, and screening newly designed drugs in _______ and ______ pharmaceutical settings

neurochemical, animal models, preclinical, clinical

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used with animals and and humans to measure specific physiological, emotional, cognitive, or other psychological processes

test/assay

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used to test spatial memory

water maze

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used to test for anxiety

elevated plus maze

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used to test for rewards

conditioned placed preference

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Ideally, tests should tap into similar ______ in humans. However, you can never truly know what an animal is _____, and must infer changes in psychological states based on changes in _______. Typically, multiple tests and ____ procedures are needed to partition complex behaviours into component processes

functions, thinking, behaviour, control

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entail some manipulation that causes some cellular/functional change that resembles what is observed in the disease

models

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manipulation in models may mimic _______ occurring in the disease (e.g. genetic, environmental), or may be ______ (pharmacological), but still induces a similar behaviour phenotype. For more complex psychiatric disorder, it is near impossible for one model to recapitulate all aspects of the disorder and multiple models are used to re-create different ______.

pathophysiology, artificial, symptoms

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seeing what causes the certain symptoms rather than the whole disorder

research domain criteria

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surgical brain lesions that permit comparison about the function of a brain area

stereotaxic surgery

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broad sucking up of the cortex that permanently destroys tissue

aspiration

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the irreversible frying of neurons, which destroys the axon as well as cell bodies

radiofrequency

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use of glutamate agonists that overexcites and selectively kills intrinsic neurons in the brain regions; does not affect axons connected to other regions; irreversible

excitotoxic lesion

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intracranial infusion of a drug via a cannula to suppress neural activity by use of anaesthetics, or GABA agonists

reversible lesions / inactivation

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Intracranial infusions similar to reversible lesions may be used to infuse _____ into specific brain regions to examine where a drug may act to affect ______. It only affects certain nuclei at a time to see what region is being affected

drug, behaviour

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NT specific _____ can be used to identify the role of the NT in a particular behaviour. The toxin is injected directly into the______, which is taken to the ______ and destroys them. Cell bodies that do not use the specific transmitters are ____ affected

neurotoxin nucleus, terminals, not

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DA, NE neurotoxin

6-hydroxydopamine (6-OHDA)

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5-HT neurotoxin

5.7-dihydroxytryptamine

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electrical stimulation that produces action potentials and NT release; can be used to assess whether activation of a nucleus induces certain patterns of behaviour; usually a complementary technique to lesions

implanted microelectrodes

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measures NTs released in a specific region while the subject is engaged in behaviour

microdialysis

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in microdialysis, artificial _____ is pumped in through a probe implanted at precise sites in brain tissue. _____ enter the solution in the probe via diffusion. Tiny amount of fluid are pumped out of the probe and analyzed by techniques such as ________. The sample rate is _____ minutes.

CSF, NTs, high performance liquid chromatography, 1-2

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used with microdialysis to separate the sample into components depending on the molecular size or ionic charge

high performance liquid chromatography (HPLC)

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can determine the concentration of molecules of interest

electrochemistry

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When a glass tip is placed in front of the membrane and suction is applied to create a small tear so that the membrane wraps around the electrode tip

intracellular patch clamp

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intracellular patch clamps allows recording of ______ _____, and changes in ____ ______ (ion flux). it provides detailed information of how drugs affect _______ ________ or ionic currents that regulate neural activity. It is measured in ____/____/_____. To use, the animal must be ____ or an in ____ brain slice preparation must be used

membrane potentials, electrical currents, synaptic transmission, mV, V, Amps, anaesthetized, vitro

When a glass or metal electrode is placed near a neuron and only action potentials are recorded

extracellular microelectrodes

With extracellular recordings, _____ cells can be recorded from at once, and this can be done in ______/_____ animals to assess changes in cell firing associated with behaviour.

multiple, awake, behaving

when a tissue sample is isolated and ground into a homogenate for analysis; often used to quantify the amount of receptors and if there are receptors there

soup methods

uses intact piece/slices of tissue to localize targets in the brain

slice method

ligands embedded in a radioactive atom (e.g. hydrogen) which can be used to index receptor binding by the amount of radioactivity in the sample, or through special photography; not the most selective

radioligands

created by injecting an antigen (e.g. receptor) into a host animal and collecting blood samples. Antibodies are tagged with coloured chemicals or fluorescent dues for visualization; harder to create, not always available

antibodies

proteins that bind to specifically targeted proteins

antibodies

When a solution containing a tissue homogenate or generic cells transfected with specific receptor is incubated with radioligand

radioligand binding

In radioligand binding, cells expressing the receptor of interest are _______ in a solution containing the radioligand. After a _____, unbound radioligand is removed and the remaining amount that is bound to the tissue is measured. It reflects the ______ of receptors in the tissue. You can use this method to identify receptors in a particular brain region by dissecting out that brain region and _______ it

bathed, washout, number, grinding

radioligand binding is also used to identify if a novel drug has some ___/_____ for a particular receptor. Only cells expressing the receptor of interest are used. A standard radioligand is combined with a _____ _____ (not radioligand), and displacement of the standard ligand at different _____ of the test are used as indexes. A wash out is needed to test how much more the test compounds ____ to the receptor. If you need a ____ concentration of test compound to bump off the standard radioligand, it is binding with stronger affinity. You can also test a drug's affinity for different receptor ________.

affinity/selectivity, test compound, doses, stick, lower, subtypes

_____ assays can be used to look at changes in ______ activity (e.g. concentration of DA on ______ receptor stimulation, and inhibition of ______) by applying different concentrations of a drug to cells to obtain a _____ function, if there is no change in ______ of receptor at different doses of ligand while also sticking to it, it is an _____

agonist, enzymatic, D2, cAMP, dose-response, 2nd messenger, antagonist

To measure enzyme activity in _____ receptors, radioligand bind must be used, while ______ (____) measures can be used for ionotropic receptors, to assess how the drug activates ionic currents mediated by the receptor. Additionally, NTs can be used in conjunction with an ______ to measure electrical change produced by it

metabotropic, electrophysiology, patch clamp, allosteric modulator

When a radioligand is incubated with tissue slices, then exposed to film sensitive to radioactivity; used to visualize receptor distribution and requires highly selective drug

receptor autoradiography

when brain slices are fixed and incubated with an antibody; which attaches to the antigen on cells that contain it; but some antibodies may lose selectivity through adding tags

immunocytochemistry

Receptor autoradiography and immunoctyochemistry work well to tell you ______ in the brain receptors are, but not to _____

where, quantify

In ELISA, proteins in different _____ are placed in a plate containing the substrate. Antibodies are linked to an _____ that acts on a substrate to form a _____ ______. The _____ is proportional to the amount to antigen present. ____ amounts of a target proteins are placed in some wells, while _______ tissue from test samples are placed in others. A computer can then be used to measure the colour to _____ the protein in an unknown sample

concentrations, enzyme, coloured product, intensity, standard, homogenized, quantify

a technique used to locate cells in tissue slices that manufacture a particular protein - detects specific mRNA molecules involved in the synthesis of target proteins

in situ hybridization

In in situ hybridization, single stranded _____ fragments that are _____ to the mRNA of interest are labelled. The amount of mRNA gives an estimate of ____ in cells at a particular time. The advantages is that it is highly ________, easier to ______, can be used when no _____ is available, and is extremely _____. Disadvantages is that just because a cell contains mRNA, doesn't mean the protein has been made, or inserted into the ____

RNA, complementary, protein, selective, analyze, antibody, sensitive, membrane

uses injected radioactive isotopes to identify areas of brain activity (blood flow, glucose, or O2 utilization) when subject is performing certain task (measure of metabolic energy)

positron emission tomography (PET)

PET has relatively low ______ resolution, as it can take up to 30 minutes for just one sample. The radioactive ligand must also be made and used _______. When combined with radiolabeled drugs that bind to NT receptors, PET can be used to study _______/_____ of those receptors in the living human brain, and _____ NT ______ by measurement of the displacement of the _______. it can also be used to index ___ NT levels. a _____ in radiotracer binding reflects an _____ in NT release. PET only works for ____, ____ and ____, and only works in places where there is high receptor and ___ levels

temporal, immediately, locations/concentrations, endogenous, release, radioligand, basal, decrease, increase, DA, 5-HT, GABA, NT

measures blood oxygenation level dependent (BOLD) signal

functional MRI

fMRI works because _____ and _____ hemoglobin have different magnetic signals. It has a better ____ and _____ resolution than PET, and can be used to measure changes in brain activity when the subject is performing certain ______, or patterns of activity across regions of ______ states

oxygenated, deoxygenated, temporal, spatial, task, resting

analyzes changes in brain function following drug administration, location and time course of drug action

pharmacological MRI

The BOLD signal may not reflect _____ of neurons within a brain region, rather it is reflective of ______ inputs to that region

firing, presynaptic

a measure of synchronous firing in large groups of neurons; readout of how groups of neurons may alter firing near simultaneously (how different parts of the brain are working together)

electroencephalography (EEG)

when characteristic waveforms in large groups of cells can be measured through the scalp due to events such as unexpected stimuli or errors

event related potentials (ERPs)

EEG's ____ resolution is better than fMRI, but has poorer _____ resolution. It is primarily used to measure _____ activity, with ____ activity being more difficult to distinguish. ERPs can be different in _____ populations, and/or can be altered by ______ drugs. This approach is being used to identify how drugs may _______ brain wave patterns

temporal, spatial, cortical, subcortical, psychiatric, psychoactive, normalize

when the gene for a protein is deleted

knockouts

when the original gene is removed and substituted for another

knockin/transgenes

Issues with genetic alterations, is _____ for the altered gene may mask the effect of the mutation, or that because altered gene function occurs at all stages of development, changes in other brain areas may be responsible for behavioural changes

compensation

selective deletion or expression of gene in only a subset of brain regions

conditional knockout

a newer approach involves _______ of a gene so that it is turned on/off when a specific drug is administered

engineering

used to deliver genetic material into targeted cells of interest

viral vectors

insertion of genes for light sensitive ion channels/pumps into neurons

optogenetics

in optogenetics, genes are inserted via _____ of engineered viral vectors into the brain region of interest. Certain viral constructs can permit greater ______ ______, for example, only expressing proteins in neurons that use a certain NT receptor, or project to a specific brain region. _____ channels expressed in neurons can be activated by light delivered via implanted optic fibers connected to laser or LED

infusions, cellular specificity, opsin

opsin channels are activated when stimulated with a specific _______ of light.

wavelength

excitatory opsin channels

channelrhodopsin

inhibitory opsin channels

halorhodopsin, Arch, NpHR

Optogenetics have great _______ specificity, as they can turn on/off a specific type of neurons for a few seconds

temporal

observed in the living organism

in vivo

measurements performed outside the living body

in vitro

tests closely resembling tests used for humans

face validity

when drug effects in the laboratory closely parallel or predict the clinical effect

predictive validity

extent to which the animal measurement tool actually measures the characteristic being investigated

construct validity

the injection of vehicle solution when the drug agent is absent from the treatment

negative control

drug that produces well-characterized effects on a given behavioural test is tested in addition to the compound of interest; determines that the behavioural test was conducted properly and is appropriately sensitive to the pharmacological manipulation

positive control

the same results recorded each time the test is used

reliability

measures of motor activity

open field test

measures of analgesia

tail flick test, hot plate test, operant analgesia testing

reduction of perceived pain without the loss of consciousness

analgesia

measure of anxiety

light dark crossing task, elevated plus maze, zero maze, novelty suppressed feeding, defensive burying

measures of fear

conditioned emotional response, fear potentiated startle

measures of depressive like behaviour

forced swim test, learned helplessness test, maternal separation, sucrose preference test

the point at which the effort required exceeds the reinforcing value

breakpoint

used to measure impulsivity

stop signal task

Stereotaxically implanted microelectrodes runs small electrical potential; changes in flow of current at electrode tup reflect changes in the concentration of electroactive substance (NTs)

in vivo voltammetry

_____ currents can be used to activate cells, or to record _____ electrical response to many neurons in a specific brain region following drug treatment or other manipulation

macroelectrode, summated

Uses 1000-20,000 distinct complementary DNA sequences on a single chip; Can screen entire genome of an organism in a single experiment on just a few chips

DNA microarrays

Either tracks the metabolic rate for nerve cell firing, or transcription factors for cell activation

autoradiography of dynamic cell processes

Either tracks the metabolic rate for nerve cell firing, or transcription factors for cell activation

autoradiography of dynamic cell processes

increases resolution of an x-ray and provides the image in 2D

computerized tomography (CT)

computerized measurement of distinct waves that different atoms emit when placed in a strong magnetic field and activated by radiofrequency waves; Distinguishes the amount of water that magnetically induces resonance of hydrogen

magnetic resonance imaging (MRI)

Uses MRI-generated data to calculate concentration of brain chemicals and evaluate metabolic changes

magnetic resonance spectroscopy (MRS)

measure diffusion of water through axons and anisotropy (direction of diffusion)

diffusion tensor imaging (DTI)

PET but using commercially available probes; Show changes in blood flow

single-photon emssion computerized tomography (SPECT)

investigates connectivity among brain regions when the individual is awake but not engaged in a task; Can be used to compare connectivity in healthy individuals and individuals with disorders

Resting state fMRI

posterior cingulate cortex, medial PFC, parietal cortex, ventral ACC

default mode network

uses guide RNA to identify a specific genomic sequence to be modified, a section of DNA is cut out, then a new one is introduced

CRISPR

isolating human genes and inserting them into mice to produce animal models of disorders

transgenic mice

Genetically engineered receptor is stereotaxically targeted to specific brain cells then activated or suppressed by administering a ligand created to bind to inserted receptor

chemogenetics