Test 2 Flashcards
What is an antipsychotic?
class of drugs used to treat psychosis - They are mostly dirty drugs, which means they bind to more than one type of receptor, but the one action they all have in common is they directly block the dopamine D2 receptor (direct dopamine receptor antagonsists)
What are atypical antopsychotics?
bind to a lot of receptors and changes the activity of receptors in different ways
- Didn’t completely cure psychosis; there were side effects
What is psychosis?
an abnormal condition of the mind that results in difficulties determining what is real and what isn’t
- Affects around 1% of the population
- Symptoms may include delusions, hallucinations, incoherent speech, and behaviour that is inappropriate for the situation
What are direct serotonin receptor agonists (receptor activators)?
- Used recreationally to cause hallucinations
- Activate serotonin 2A receptors, which are inhibitory metabotropic receptors expressed by neurons all over the brain
- But other direct serotonin 2A receptor agonists do not cause hallucinations at all
- For a long time, people did not understand why some 5HT-2A receptor agonists caused massive hallucinations while others did nothing of the sort
What is biased agonism?
• When a metabotropic receptor ligand causes the receptor to preferentially activate one type of intracellular g protein, whereas another ligand at the same receptor might preferentially activate a different g protein
- Different ligands binding to each receptor
What are direct agonists/antagonists?
drugs that affect postsynaptic receptor activity by directly binding to postsynaptic receptors
What are indirect agonists/antagonists?
drugs that affect postsynaptic activity in an indirect manner; the proteins they bind to are not postsynaptic receptors
What is a receptor agonist?
drug that directly or indirectly increases the activity of postsynaptic receptor proteins
What are drugs?
exogenous chemicals that at low doses significantly alter the function of certain cells
What is a competitive agonist?
acts similarly to the endogenous NT; it activates the receptor by binding where the neurotransmitter normally binds
What is a competitive antagonist?
attaches to the same binding where the neurotransmitter normally binds, but it doesn’t activate the receptor
- Competitive antagonists are full antagonists
What will the competition for a binding site between an endogenous NT and an exogenous drug will depend on?
their relative concentrations and their affinity for the binding site
What is non-competitive binding?
• When a drug binds to a receptor at a site that does not interfere with the binding site of the principal ligand
- It’s possible for a NT to bind on one site of a receptor while a drug binds on another
What is a non-competitive agonist?
it fully or partially activates the receptor
What is a non-competitive antagonist?
fully blocks receptor activation; it doesn’t compete for the NT binding site
- It “wins” without competing by binding to an alternative site
What are allosteric modulators?
non-competitive drugs that only influence receptor activity when the NT is also bound to the receptor
What are negative allosteric modulators?
reduce the effect of the primary ligand
What are positive allosteric modulators?
amplify the effect of the primary ligand
What is Parkinson’s disease?
a neurological disorder that is characterized by tremors, rigidity of limbs, poor balance, and difficulty initiating movements
- It’s caused by the degeneration (death) of dopamine neurons in the midbrain
How is dopamine made?
Made from tyrosine –> (enzyme) –> L-DOPA –> (enzyme) –> dopamine
How are conventional NTs made?
made in axon terminals and are made from precursor molecules (generally from amino acids)
- In some cases, precursor molecules can be administered as drugs since they can increase the amount of NT that is made and released precursors act as receptor agonists
What is the synthesis of NT form precursor molecules is controlled by ?
Enzymes
- Some antagonists work by blocking these enzymes, thus reducing production of the NT so there is less in each vesicle
What is the clearance of NTs from the synapse is controlled by?
reuptake transporter proteins and enzymatic deactivation
What is the therapeutic index?
the ratio between the dose that produces desired effect in 50% of animals and the dose that produces toxic effects in 50% of animals
What is tolerance?
when an effect of the drug diminishes because of repeated administration
- The body’s attempt to compensate for the effects of the drug
- Not all drugs show the same degree of tolerance
- Withdrawal symptoms: opposite effect of the drug
What is sensitization?
when a drug becomes more and more effective through repeated use
What is a dopamine D2 receptor?
an inhibitory metabotropic receptor expressed by neurons all over the brain
What is affinity?
the probability and tightness of ligand-receptor binding (in most cases it’s the NT)
What is a CT scan?
- A computer assisted x-ray procedure is used to take a photo of the brain
- The x-ray bean is delivered from all angles and a computer translates the information received from the x-ray detector into a series of pictures of the skull and brain (the densest tissues)
- Relatively cheap and fast, the resolution is not great for soft tissue like brain
What is an MRI?
- Uses strong magnetic fields instead of x-rays
- When molecules of the body are in a strong magnetic field, the hydrogen atoms spin with a particular orientation
- A radiofrequency wave is then passed through the body, which knocks the hydrogen atoms out of their orientation
- As they return to the orientation set up by the magnet, they emit their own radio waves that are detected by the scanner
- The scanner can estimate the density of hydrogen atoms in each area of the brain (they are most prevalent in fat and water) by calculating the amount of radio waves that come out of each region after each pulse of radio wave energy is delivered
- RESULT: high spatial resolution, 3-dimensional image of the brain
What is diffusion tensor imaging (DTI)?
- An MRI technique that measures the direction and speed of the diffusion of water molecules
- Used to identify axon tracts
- Colors indicate the direction of water molecule diffusion
What is an fMRI?
- We can see the flow of oxygenated blood by determining where the iron atom in hemoglobin is bound to oxygen and where it is not (correlates with neural activity)
- Technique is popular because it doesn’t use needles, surgery, or radioactivity
- It provides both structural and functional information with decent spatial resolution and temporal resolution
What is a PET scan?
- The person is injected with radioactive compound to detect changes in energy use over time
- The computer determines which regions of the brain have taken up the radioactive substance and produces a picture of the brain showing different activity levels
- early studies used 2-DG, but now we use L-DOPA or radioactive ligands
What is 2-DG?
Similar to glucose, since it is taken up by energy consuming cells in the body
- However, 2-DG is not broken down (metabolized) as easily as sugar is, so it stays around for hours
What is L-DOPA?
- L-Dopa is picked up by dopamine neurons, converted into dopamine, and released as normal
- With a PET machine it’s possible to see where the radioactive dopamine went
What are macroelectrodes?
- Used to record activity of a large number of neurons in a particular region of the brain
- Measure the effect of action potentials and post synaptic potentials (synaptic transmission) from millions of cells located around the electrode
- They are attached to an amplifier which records an electroencephalogram
What is an EEG?
Provides a measure of gross activity in the brain
- Provide a diagnostic tool which particular states of consciousness or types of cerebral atrophy are associated with specific patterns of EEG waveforms
What is an experimental ablation (lesion study)?
involves the removal or destruction of a portion of the brain, presumably the functions that can no longer be performed following the surgery are the ones the brain region normally controls
What are radiofrequency lesions?
Small lesions can be made by passing radiofrequency current through a metal wire that is insulated everywhere but the tip
- This electric current produce heat that burns cells around the tip of the wire
- The size and shape of the lesion is determined by the duration and intensity of the current
• Downside: axons just passing through will also be burned
What is a excitotoxic lesion?
Brian lesion produced by intracerebral injection of a glutamate receptor agonist
- cause so much excitation and calcium influx that the affected neurons often undergo apoptosis
- axons passing through are usually spared
What is a sham lesion?
Placebo procedure that duplicates all steps of producing brain lesion except it doesn’t cause extensive brain damage
What is a reversible lesion?
A temporary brain lesion that can be achieved by injecting drugs that block or reduce neural activity in a given region
To target cell bodies, what do drugs need to do?
the drugs need to target receptor proteins, not the proteins in action potential (ex: GABA receptor agonists)
What are microelectrodes?
Thin metal wires with a fine tip that can record the electrical activity of a single neuron (known as single-unit recording)
- Electrodes are implanted in the brains of animals using stereotaxic surgery
- The wires are connected to a socket and the animals can be ‘plugged in’ to a recording system
What is electrical stimulation?
Involves passing an electrical current through a wire inserted into the brain
- This will affect everything in the area (cell bodies and fibers of passage)
- Some electrical stimulation patterns (often very high frequencies) counterintuitively, tend to produce the same behavioural effect as lesioning the brain area
- Depolarizes everything
What is chemical stimulation?
Achieved with drugs
- In rodents, drugs are often administered through a guide cannula (hollow tube)
- Anesthetics can be injected to shut down all neural activity
- Alternatively, the drug may interact with receptor proteins, which will avoid the fibers of passage
What are optogenetics?
The use of light to control neurons which have been made sensitive to light through the introduction of foreign DNA
This foreign DNA encodes opsins
What are opsins?
Light-sensitive proteins
- The opsins we have in our eye are metabotropic receptors that operate with a 30-millisecond delay
- Often ion channels that open and close instantly in response to light
- The original ones were discovered in bacteria in different parts of the world
What is a virus?
Small infectious agent that replicates inside the cells of other organisms
- They cannot replicate without the help of others and they can’t read their own DNA; they inject it into a cell
- The DNA of a virus encodes instructions on how to make more virus
What is a replication deficient virus?
A virus that can’t do anything
- This happens when we remove the DNA from the virus
What is GCaMP?
Researchers modified GFP causing it to bind calcium and fluoresce much brighter when it does
- monitoring GCaMP fluorescence is a good way to measure neural activity (in cells made to express GCaMP protein)
What is retrograde labeling?
Tracing afferent (conducting inward) axons
used to label the cells that innervate (project to) a given region
- Various chemicals, such as fluorogold can be used as a retrograde tracer
- Fluorogold molecules are taken up by axon terminals and transported back to the cell body
What is anterograde labelling?
Tracing efferent (conducting outward) axons
used to label where axons from a particular location go to
- Various chemicals, such as PHA-L, can be used as an anterograde tracer
- PHA-L molecules are taken up by cell bodies and transported down to axon terminals
What is stereotaxic surgery?
• A surgical intervention that uses a stereotaxic apparatus
- It is used to inject things into the brain, such as drugs, viruses, or tracer molecules
- It is also used to permanently implant things, like cannula, electrodes, or fiber optic cable
- bregma used as a reference point
What is bregma?
the junction point where pieces of skull fuse together
What is micro dialysis?
• Measures signalling molecules in the brain
• Dialysis: refers to the use of an artificial semipermeable membrane to either deliver molecules to or measure the amount of molecules in some solution or brain area
- It takes time for the concentration of molecules to equilibrate across a dialysis membrane, so the fastest sampling rate possible is once per minute
What is immunohistochemistry?
• A histological method that is used to label proteins and peptides in biological tissue
- most common technique that takes advantage of antibodies and makes fluorescent bodies
What are immediate early genes?
genes that tend to be expressed following periods of elevated spiking activity (ex: c-Fos)
What are sensory receptors?
• Also known as sensory neurons, they are specialized neurons that detect a specific category of physical events
- They accomplish this task with receptor proteins that are sensitive to specific sensory stimuli
What is sensory transduction?
process by which sensory stimuli are converted into receptor potentials
What is receptor potential?
graded change in the membrane potential of a sensory neuron caused by sensory stimuli
What is a photoreceptor cell?
The sensory neuron responsible for vision
- located in the retina, they convert the electromagnetic energy of photons into receptor potentials
- each cell contains one type of opsin, so we have 4 types of photoreceptor cells
What is a rod photoreceptor cell?
they express the rod opsin (rhodospin)
What is a cone receptor cell?
they express one of the cone opsins (red, blue, or green)
What is retinal?
Small molecule synthesized by vitamin A that binds to opsin proteins
- type of light that it can react to is dependent on the opsin protein that retinal is bound to
What is visible light?
electromagnetic energy that has a wavelength between 380 and 760 nm
- We detect this light using four kinds of photoreceptor cells (1 rod cell and 3 cone cells)
• The energy in visible light is strong enough so that the electron will absorb it and hold onto the energy
What is a self-propagating wave?
The less it hits something, the more it will continue throughout the entire universe
- The waves always propagate at the same speed
- Photon is generated when there is an acceleration of a charged atom that creates the disturbance to create the self-propagating wave
What is ionizing radiation?
• High energy light doesn’t interact with matter very much
- It will knock the electron out of the molecule –> molecules left over are positively charged and highly reactive
- Can cause death or cancer
What is an x ray?
ionizing radiation, but it’s not as bad
- They go through the non-dense parts of your body
What are ultraviolet (UV) rays?
Still powerful enough to knock electrons out of the molecule
Ex: sunburns
What are TV and radio signals?
- Very low energy light
- When it hits you, it’s not strong enough to do anything your body will notice
- It can heat up the body a little bit
What is the red cone opsin?
First opsin evolved
- Holds on to retinol molecule
- Can absorb light from 500-700 nm
- You can only detect if there’s light, not colour
- You can see red
- Most sensitive to LONG wavelengths
What is the blue cone opsin?
- Holds on the retinol molecule in a different way
- Can absorb light from 400-500 nm
- Gives rise to colour vision (long wavelength or short wavelength)
- You can see purple light
- Most sensitive to SHORT wavelengths
What is the green cone opsin?
- Most sensitive to MEDUIM wavelengths
- Once you have all 3 opsins, you can see the entire rainbow
- You perceive colour by the relative activation of the others
What is rhodopsin?
- Perfectly optimized
- Makes retinol extremely sensitive to all waves of light (100x more)
- ROD cell class
- Peripheral vision is filled with rod cells
What is the fovea?
Where we can see colour (mostly cone cells), each of which connects to a single downstream collection of cells (a bipolar cell which in turn connect to a single ganglion cell)
- Thus, photoreceptors in the fovea can register the exact location of the input
- This enables high resolution, color vision
What is protanopia?
Absence of red cone opsin
- visual sharpness is normal because the red cone cells get filled with green cone opsin
- people with condition have trouble distinguishing colours in the green-yellow-red section of spectrum
What is deuteranopia?
Absence of the green cone opsin
- visual sharpness is normal because green cones get filled with red cone opsin
- people with condition have trouble distinguishing colours in the green-yellow-red section of spectrum
What is tritanopia?
Absence of blue cone opsin
- blue cone cells are not compensated for by other cells, but the blue cone opsin is not that sensitive to light
- SO, visual acuity (sharpness) isn’t really affected
What are bipolar cells?
Do not have action potentials and release glutamate in a graded fashion dependent on their membrane potential
• Two main types: OFF bipolar cell and ON bipolar cells
- OFF: express ionotropic glutamate receptors, so they are depolarized by glutamate (more active in dark)
- ON: only have inhibitory metabotropic glutamate receptors, so they are uncommonly inhibited by glutamate (more active in light)
What are retinal ganglion cells (RGC)?
typical neurons; they have action potentials and are generally excited by glutamate
What is the receptive field of a neuron?
somewhere in the visual space where you can shine light to change the activity of that neuron
- Defined in relation to the fixation point
What are simple cells (in primary visual cortex)?
sensitive to lines of light, and their receptive fields are typically organized in a center-surround fashion
- They sum up all the information that they’ve received from other cells
What is the visual association cortex?
Part of the occipital lobe that surrounds primary visual cortex
• Each area responds to particular features of the visual environment, such as particular shapes, locations, movements, and colors
- Each region forms one or more independent maps of the visual field
What is the dorsal stream of the visual association cortex?
Involved in identifying spatial location and encodes where objects are, if they are moving, and how you should move to interact with or avoid them
What is the ventral stream of the visual association cortex?
Involved in identifying form (shape) and encodes what the object is and its colour
What is stereopsis?
the perception of depth that emerges from the fusion of two slightly different projections of an image on the two retinas
What is retinal disparity?
The difference between the images from the two eyes
- results from the horizontal separation of the two eyes
What is agnosia?
a deficit (problem) in the ability to recognize or comprehend certain sensory information, like specific features of objects, persons, sounds, shapes, or smells, although the specific sense is not defective nor is there any significant memory loss - relates to a problem in some sensory association cortex not to problems that relate to the sensory neurons or to the primary sensory areas
What is akinetopsia?
a type of visual agnosia by damage in area of the dorsal visual stream (in the parietal lobe of the cerebral cortex)
- A deficit in the ability to perceive movement
What is cerebral achromatopsia?
a visual agnosia caused by damage to the ventral visual stream (in the temporal lobe)
- People with this deny having any perception of COLOUR; they say everything looks dull and that it is all shades of grey (they weren’t born like this, due to damage later in life)
- they can’t remember the colour either as the neurons are damaged
What is prosopagnosia?
failure to recognize particular people by sight of their FACES; caused by damage to the fusiform gyrus (fusiform face area)
- People with this identify others by other features (hair, perfume, etc.)
What is the somatosensory system?
• Provides information about touch, pressure, temperature, and pain, both on the surface of the skin and inside the body
What is the exteroceptive system?
(cutaneous/skin senses) responds to external stimuli applied to the skin (ex: touch)
What is the interoceptive system?
system (organic senses) provides information about conditions within the body and is responsible for efficient regulation of its internal milieu (ex: heart rate, breathing, hunger, bladder)
What is the proprioceptive system?
(kinesthesia) system monitors information about the position of the body, posture and movement (ex: the tension of the muscles inside the body)
What are the high-threshold mechanoreceptors (pressure receptor cells)?
free nerve endings that respond to intense pressure, like something striking, stretching, or pinching the skin
Where does poorly localized information go?
immediately crosses over in the spinal cord and the first synapse is there
- This information then ascends to the thalamus through the spinothalamic tract
Where does highly localized information (ex: fine touch) go?
ascends ipsilaterally through the dorsal column of the spinal cord (blue)
- The first synapse in this pathway is the medulla; from there the information crosses over to the contralateral side as it ascends to the thalamus
What is tactile agnosia?
• Patients with tactile agnosia have trouble identifying objects by touch alone
- When touching an object, people might make false conclusions about the object
- However, these patients can often draw objects that they are touching, without looking, and they can sometimes identify objects from their drawings
What is phantom limb syndrome?
- A form of pain sensation that occurs after a limb has been amputated
• Amputees report that the missing limb still exists and that it often hurts
• Perhaps due to confusion in the somatosensory cortices - The brain gets nonsense signals (in part from the cut axons) and it has difficulty interpreting them
What kind of receptor is associated with an umami taste?
metabotropic glutamate receptor
What activates both salt and umami receptors?
MSG (monosodium glutamate)
What is saltiness due to?
Ions
What is sourness due to?
pH level; also detects carbonation
What is fat taste due to?
fatty acids, lipid molecules
What is olfactory epithelium?
The tissue of the nasal sinus that sits underneath the skull (the cribriform plate) and contains olfactory receptor cells
- Each olfactory cell expresses only one type of olfactory receptor protein
What is loudness?
amplitude or intensity of the molecular vibrations
What is pitch (tone)?
frequency of the molecular vibrations
- Measured in hertz (Hz) or cycles per second
What is timbre?
complexity of the sound
- We use timbre to help identify the source of the sound wave (through learning processes)
What is the basilar membrane?
• Encodes high notes on the end closest to the oval window and low notes deeper in the cochlea
Where are the cells that are transducing stimuli into sound located?
located in the organ of Corti
What are inner hair cells?
- Inner hair cells are the ones transducing the information
- Cilia are not attached to top membrane; when water ripples, they will wave around, causing ion channels to open or close
What are outer hair cells?
Outer hair cells are physically connected to top and bottom membranes
- They act like muscles; they can contract or expand
- They determine how much bending there will be
- They regulate the sensitivity and frequency selectivity of inner hair cells
What are tip links?
elastic filaments that attach the tip of one cilium to the side of adjacent cilium
- They do NOT have axons
What is an insertional plaque?
• The point of attachment of a tip link to a cilium
- Each insertional plaque has a single ion channel in it that opens and closes according to the amount of stretch exerted by the tip link
What is place encoding?
Encoding of different frequencies of sound on hair cells at different points on the basilar membrane
What is rate coding?
System by which information about different frequencies of sound waves is coded by the firing rate of neurons in auditory system
- Encodes how much NT is being released from the hair cells as a population
What is pitch perception?
moderate to high frequencies are encoded by place coding / low frequencies are partly encoded by rate coding
What is an overtone?
sound wave frequencies that occur at integer multiples of the fundamental frequency
- adds complexity to the sound wave
How do we detect the source of high-pitched sounds?
by analyzing DIFFERENCES in loudness between the ears
How do we detect the source of low-pitched sounds?
we look at TIMING
What is tonotopic representation?
The organisation where the different frequencies of sound are analyzed in different places of the auditory cortex
What is amusia?
Inability to perceive or produce melodic music
- These people can often converse and understand speech and recognize environmental sounds
- They can even recognize the emotions conveyed in music, but they will typically be unable to tell the difference between consonant music (pleasant sounding harmony) and dissonant music (unstable, transitional) even though these sounds might alter their emotional state just as they do in other people
What is the vestibular system?
Detects gravity and angular acceleration of the head
- Does not produce any readily definable, conscious sensation
- Instead, it maintains your upright head position, organizes your balance, and corrects eye movements to compensate for head movements
- Has cilia that activates ion channels
What are semicircular canals?
3 ring-like, fluid-filled structures that detect changes in head changes in head rotation (angular acceleration)
What is cupula?
gelatinous mass found in the ampulla of the semicircular canals; moves in response to the flow of fluid in canals
What are the utricle and saccule in the vestibular sacs?
respond to the force of gravity and inform the brain about the head’s orientation
What is otoconia?
Heavy mineral
- Sits on top of cilia and naturally falls, activating different groups of hair cells
