Flashcards in Lecture 6 Deck (81):
What justifies animal studies?
- Minimized pain and discomfort
- The value of the information gained from the research
- The importance of science for understanding ourselves and animals
What is experimental ablation?
- it involves the destruction of brain tissue followed by an assessment of subsequent changes in behavior
What do ablation techniques include?
- Electrolytic lesions/radio frequency
- excitotoxic lesions
- temporary 'lesions' by muscimol injection
What happens during ablation studies?
- brain lesions are studied in order to determine which behaviors have been inhibited
What is stereotaxic surgery?
- type of surgery done with animals in order to place electrodes on lesions of the brain to determine what behaviors have been inhibited
What is the sterotaxic instrument?
- holds the head in a fixed position
- allows the surgeon to position an electrode or other device within a particular sub-cortical structure
What is the stereotaxic atlas?
- provides a series of drawings of brain structures
- each page is a section of the brain relative to a landmark on the skull (such as bregma)
How does the stereotaxic atlas to target a brain region?
- hole will be drilled here above target of lesion
- page indicates distance from bregma
- once we have the bregma, then we have the landmark
What are Histological techniques?
- used to verify the placement of a lesion within the brain
What is the Histological technique process?
1) Prefuse the brain
2) Fix the brain
3) Use different strains
What is Prefuse?
- Remove blood from the brain
What is fixing the brain in the histological technique?
- fix brain in formalin to solidify tissue and to prevent autolysis
- slice the brain into thin sections and then freeze the rest
What doe we mean by "use stains" in the histological technique?
- use stains to highlight selective neural elements
- Myelin (Weil stain)
- cell body (cresyl violet)
- membrane (golgi stain)
Tracing Neural connections?
- neurons in a given regon send axonal (efferents) to other brain regions and receive axonal inputs (afferents)
How are efferent connections done?
- done by using anterograde labels that are taken up by the cell bodies and transported to axons
- "forward: toward the axons from the cell bodies"
- Inject PHA-L into a nucleus, wait a few days, process the brain tissue
- Immunocytochemistry uses a radioactive antibody to PHA-L in order to identify cells contaning PHA-L
How are afferent connections done?
- done by using retrograde labeling
- "Backwards: from the terminal buttons to the cell bodies"
-flurogold is a retrograde tracer
What are the results of Tracing methods?
- Anterograde tracing: Inject PHA-L in VMH
- Then see axons and terminals in PAG
- Retrograde tracing inject flurogold in VMH
- Then see cell bodies in medial amygdala
What the two types of neuroimaging techniques?
- structural and functional methods
What are the types of structural neuro imaging techniques?
- Computerized tomography (CT)
- Magnetic Resonance Imaging (MRI)
What are the types of functional neuroimaging techniques?
- Position emission tomography (PET)
- Functional Magnetic Resonance Imaging (fMRI)
- Electrical Methods (EEG, ERG)
Property measured, strengths, and weakness of CT scan?
- amount of radioactivity that passes through tissue
- Cheap and quick
- Spatial resolution is poor and there is radiation exposure
Property measured, strengths, and weakness of MRI?
- Energy released by hydrogen atoms in response to radio frequency
- High spatial resolution
& Distinction between different tissue 'compartments'
- Discomfort for participant
Property measured, strengths, and weakness PET scan?
- uptake of radiotracer (e.g., fluoxyglucose)
- Can image energy consumption or neurotransmission & good spatial resolution
- COSTS, ionizing radiation, temporal resolution poor
Property measured, strengths, and weakness of fMRI?
- changes in blood-oxygen dependent (BOLD) response
- No radiation, excellent spatial radiation
- Temporal resolution modest, discomfort for participant
Property measured, strengths, and weakness of EEG and ERP?
- Fluctuations in electrical activity over time or in response to specific stimulus
- Costs, no radiation, excellent temporal resolution (w/in milliseconds)
- Poor spatial resolution
What is a CT scan?
- uses an x-ray beam to scan the brain from all angles, these scans are then summarized in an image of skull and brain (in horizontal plane)
What is an MRI?
- uses a magnetic field and radio waves to excite hydrogen molecules, the resting information is combined to form an image of tissue
- can see both white and gray matter
What is DTI?
- This is a sensitive probe of cellular structure measured by diffusion of water molecules
- the diffusion of molecules is generally isotopic (equal in all directions)
What is the key to DTI?
- anistropy: variability of diffusion directionally in relation to tissue structure.
- 3 dimensional vector that measures the direction of the water
- the higher the fraction, the more they interact with matter fibers
What is the PET can a variation of?
- the animal 2-DG technique
- What is the 2-DG technique?
- Human subject is injected with radioactive 2-DG, which is taken up by brian cells
- As the radioactive molecules decay they emit positrons that can be detected by scanner
What are PET scans be used for?
- PET scans be used to characterize neurological disease, monitor treatment, and depict task-related activation patterns. PET is highly sensitive to preclinical disease
What are some typical PET targets?
- glucose consumption, dopamine synthesis, amyloid plaques and glucose consumption
What is a marker for Alzeimer's disease on a PET scan?
- temporal parietal region chunk seeing hypometabolism developing
What is the difference between a normal brain scan and a brain with Alzeimer's?
- you will see more activity in the regions of the brain, these have more amyloid deposits in these areas
What is the difference in people from the same family where one person may have AD?
- one person has GRN mutation carrier and another person does not.
- You will notice a early imbalance in the anterior and posterior activity of the brain
What is the difference in pre and post treatment with L-dopa in a person with Parkinson's disease?
- pre-treatment: dopamine synthesis in the basal ganglia is reduces
- post-treatment: dopamine synthesis in increase
How does one record neural activity?
- axons conduct action potential which are measurable electrical impulses
What is the function of microelectrodes?
- measure electrical activity from single (single-unit recording) or a few neuron(s)
What is the function of macroelectrodes?
- record the summated electrical activity of large regions of the brain
- Surface electrodes placed on human scalp are used to record brain activity (EEG)
What is metabolic activity?
- increases in neural activity are associated with increases in metabolic activity in a brain region
How is a Fos protein produced?
- produced in the nucleus when a neuron is activated
How is a Fos protein measured?
- measured just after a behavior of interest has occurred
What happens with neurons with increase fos levels?
- neurons with these elevated levels are active during that behavior
What is stimulating neural activity?
- neurons in a region can be artificially activated to assess the role of that region in behavior
What is electrical stimulation?
- involves electrical current through a wire inserted in the brain
What is chemical stimulation?
- can involve infusion of an excitatory amino acid such as glutamate into a region
- this is much more aggressive
- implanted into a region can be used to deliver rug solutions into that region
- chemical stimulation can be more specific than electrical stimulation
What is photostimulation?
- takes advantahe of the light sensitivity of certain proteins that can be introduced selectively into neurons and made to control ion channels
What occurs if a blue light is applied in stimulation of neural activity?
- sodium and calcium ions rush into the cell and depolarize the membrane
What occurs if the yellow light is applied in stimulation of neural activity?
- chloride ions move into the cell, causing hyperpolarization
What are neurochemical methods?
- these methods are applied to brain tissue using immunocytochemisty
- They allow identification neuronal populations that use a given neurotransmitter.
What is emotion?
- an instinctive or intuitive feeling as distinguished from reasoning and knowledge
How can emotion refer to response?
- behavioral: muscle response (face, body, action)
- autonomic: sympathetic activation
- hormonal: secretion of stress hormones
How can emotion refer to feelings?
- negative: anxiety, fear, anger, etc.
- positive: joy, love (these are rarely studied)
What is the hub of emotion?
- this is part of the limbic
What is the primary role of the amygdala?
- plays a special role in physiological and behavioral reactions to objects or situations that have biological significance
- it reacts to situations very quickly
What does the amygdala coordinate with?
- coordinates and integrates the behavioral, autonomic and hormonal components of emotional responses
What is the nuclei that is the most important for emotional responding?
- the central nucleus
What are the nuclei that are part of the amygdala?
- central nucleus, basal nucleus, lateral nucleus
What is the function of the lateral nucleus?
- gets all of the information
What is the function of the basal nucleus?
- input from the lateral nucleus gets transferred into the basal nucleus
The amygdala receives input from which of the following areas of the cortex?
- the ventromedial prefrontal cortex: emotional regulation
- thalamus: sensory input
- hippocampal formation: memory
The amygdala projects to which of the following areas?
- thalamus to prefrontal cortex
- ventromedial prefrontal cotex
- hypothalamaus, midbrain, pons, medulla: which control various aspects of emotional responses
How do lesions in the central nucleus diminish emotional responses?
- reduced fear responses to threat stimuli
- reduced chance of developing ulcers to stress
- reduced levels of stress hormones
What does electrical stimulation of the central nucleus do?
- induces fear and agitation
What is a conditioned emotional response?
- fear stimumi elicit emotional response: painful stimuli
- fear stimuli is associated with a neutral stimuli: tone prior to the shock
- with repeated exposure, the neutral stimulus will elicit an emotional response
- tone previously paired with shock will not elicit a fear
What parts of the amygdala are involved in a conditioned emotional response?
- the lateral nucleus, central nucleus,basal nucleus and their outputs,
What is extinction?
- when extinction of the CER occurs and it relies on the inhibitory processes in the ventromedial prefrontal cortex
What is urbach-wiethe disease?
- a rare autosomal recessive disorder that causes skin abnormalities and bilateral calcifications in the medial temporal lobes including the amgdala
- an an example of a person with this disorder would be a person with no fear (case of SM)
What occurs with people who have Alzheimer's disease and have a destroyed amygdala?
- people have a hard time recalling memory and events
What three areas are involved in aggression in animals?
- periacqueductal gray matter
Which hormone seems to inhibit aggression in animals?
- low 5-HIAA levels predicts risk-taking behavior and long-term survival in preadolescent male monkeys
- What is associated with aggression and antisocial behavior?
- Low 5-HT levels.
- men with low levels of 5-HT activity are more likely to have relatives with antisocial behavior
What medication (SSRI) is responsible for decrease irritability and aggressiveness?
What is the connection between serotonin and the prefrontal lobes?
- decreased activity of serotonin neurons associated with increased risk taking aggression
- PFC activated by large Serotonin pathway
What is noticed in people with a history of impulsive aggression?
- fMRI study showed lower 5-HT transporters in medial prefrontal area
- fluoxetibne treatment produced increased activity of prefrontal cortex on fMRI and decreased aggresion
What happened with phineas gage?
- damage to the ventromedial prefrontal cortex and caused him to change his personality.
- became childish and annoying to others
What occurs in the network connection of the vmPFC and the amygdala ?
- the network works bidirectionally
What occurs in people who have damage to their vmPFC?
- people can assess a situation in a theoretical sense but fail in real-life situations
- these people do not use emotion when assessing a real life situation
What occurs with moral judgement and damage to the vmPFC?
- people in this context would choose to kill one person to save all people dues to the fact that they are using knowledge and not emotion when making this judgement