PSYC 304 Final Part 1 PDF
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This document discusses various animal models used in psychological research, including techniques such as Transcranial Magnetic Stimulation (TMS) and the Morris water maze. It also details the practical considerations for behavioral assays in animal models, like the Forced-Swim Test (FST) and T-maze.
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Transcranial Magnetic Stimulation - r TMS is repeated transcranial magnetic stimulation - Uses magnetic fields to induce electrical changes (changes in how brain activity works) - rTMS is usually targeted towards the cortex and briefly “turns off” one part of th...
Transcranial Magnetic Stimulation - r TMS is repeated transcranial magnetic stimulation - Uses magnetic fields to induce electrical changes (changes in how brain activity works) - rTMS is usually targeted towards the cortex and briefly “turns off” one part of the brain -> rapidly inducing a “Virtual lesion” - Used for potential therapeutic applications such as treatment resistance depression Deep Thoughts by the Rat - xamples of using rats as animal models for studies E - Morris Water Maze - A rat is placed into a pool of opaque water (chalky, non-transparent water). - Just below the water's surface, there is a small hidden platform. - Initially, the rat swims around randomly until it stumbles upon the platform, allowing it to stand and rest out of the water. - Measured Variable: The time it takes for the rat to find the platform. - With repeated trials: - The rat takes less time to locate the platform. - Its swimming route becomes more direct. - The walls of the pool have visual "markers" (e.g., stars, trees) to help the rat with spatial navigation. - This experiment studies spatial learning, which is highly hippocampal-dependent. - Hippocampal disruption: Rats with hippocampal damage show significant difficulty finding the platform. - 5-Choice Serial Reaction Time Task - Conducted in an operant chamber (Skinner box) with 5 holes on one side of the chamber. - Task: - Each hole contains lights. - The rat must identify which hole lights up and poke its nose into the correct hole. - Correct response → Sugar reward. - Variables: - Accuracy: Operationalized as a measure of attention. - If the light is on for a very short time, the rat must pay close attention to succeed. - Impulsivity (e.g., motor impulsivity): - At the start of the trial, rats must wait and not poke their heads into any holes before the lights fire. - If the rat pokes prematurely → Timeout penalty (5 seconds in the dark). - Key Focus: - Attention: Success depends on the rat’s ability to focus on the lit holes. - Impulsivity: Failure to wait for the light demonstrates impulsive behaviour. - T-maze: - Animals runs down to the junction and makes a choice between running into 2 arms of the maze The Quality of Your Behavioural Assay Forced-Swim Test (FST) Setup: ○ An animal is placed into a pool withno platformandno means of escape. ○ The animal is left in the pool until it stops swimming. Purpose: ○ Behavioural assay to testdepression-like symptoms. ○ Used to assess the efficacy ofantidepressant medications. Concept: ○ Animals that are “depressed” willstop swimming earlierthan those that are not depressed. Limitations: ○ Repeated Trials: With repeated exposure to the FST, animals may develop a strategy to stop swimming immediatelyto signal the researcherto remove them from the water. ○ Results can be difficult to interpret, especially when comparingsimple vs. complex behaviours. Why Use Animal Models - ehavioural Similarity: Animal behaviours canclosely model human behaviours, B making them useful for research. - Brain Similarities: - Rat and human brains share similarorganization andstructures. - Differences: - Example: Theprefrontal cortexin rats has a differentorganization and structure compared to humans. - Animal Cognition: - Animal cognition is moresophisticatedthan previously assumed by humans. Drug “Challenge” Administering Drugs in Animal Models D rugs are usually administeredacutelybut can also be givenchronically. Common Routes of Administration(primarily via injection): 1. Intramuscular (IM) ○ Location: Shoulder muscle. ○ Advantages: Rapid entry into the bloodstream → quick effects on the brain. ○ Disadvantages: Most drugs do not match the muscle’s pH → can causepain, soreness, and disrupt the animal. 2. Intravenous (IV) ○ Method: Injection into a vein, often using acatheter. ○ Advantages: Used fordrug self-administration studies. ○ Disadvantages: Risk of the animalremoving the catheteraccidentally. Potential forinfectionat the catheter site. 3. Subcutaneous (SC) ○ Method: Injectionjust under the skin. ○ Advantages: Minimally disruptive; rats have ample loose skin for easy injection. Causes minimal pain. ○ Disadvantages: Slower absorption into the bloodstream → delayed andsubdued effects. 4. Intraperitoneal (IP) ○ Method: Injection into theabdominal cavity. ○ Advantages: Minimally disruptive. Quick absorption into the blood (slightly slower than IM). 5. Intraventricular ○ Method: Injection directly into thebrain ventricles. ○ Purpose: Allows drugs to bypass theblood-brain barrier. Dose-Response Curve Most drugs exhibit adose-response relationship: ○ Example:Alcohol→ small doses may act as a stimulant(e.g., increased energy), but higher doses producedepressive effects. Human Limitations: ○ In humans, giving multiple doses is restricted due toethical and experimental constraints. Within-Subjects Design In this design, asingle animalis exposed to all conditions (e.g., no dose, low dose, high dose). Advantages: ○ No need for separate control and experimental groups. ○ Reduces the number of animals needed. Placebo Note: ○ In animal models, we do not use the term“placebo”because animals do not understand the concept. Invasive Electrical Recording Methods - Intracellular Unit Recording - Description: Records activityinside a single cell. - Challenges: - Very difficult, especially inawake and behaving animals. - Movement can cause electrodes todislodgefrom thecell. - Extracellular Unit Recording - Description: Records activityoutside the cell(notwithin the cell membrane). - Advantages: - More common and reliable. - Electrodes are more stable andstay in placebetterthan intracellular recordings. - Multiple-Unit Recording - Description: Simultaneous recording fromgroups ofelectrodes(typically 4). - Purpose: Allows monitoring of activity from multipleneurons at once. - Invasive EEG Recording - Description: Places EEG electrodesvery close to the brain. - Example Use: Studyingsleepin animal models. Stereotaxic Surgery P urpose: Used to access specific brain regions forprocedures (e.g., lesions, optogenetics, electrode implants). Tools: ○ Stereotaxic Atlas: A detailed atlas of the brain (down to tenths of a millimetre). ○ Bregma: Point on the skull where the bones fuse; serves as a reference point. Example: "The amygdala is 2.5 mm ventral to bregma." Verification: The animal is sacrificed after surgeryto confirm targeting of the correct brain structure. Lesion Methods Chemical Lesions: Excitotoxic Lesions: ○ Chemicals:Quinolinic acid,Ibotenic acid. ○ Mechanism: Excess excitatory chemicals cause toxic damage to neurons. Selective Chemical Lesions: ○ Chemicals: 6-Hydroxydopamine (6-OHDA)→ targets dopamine. 5,7-Hydroxytryptamine→ targets serotonin. ○ Effect: Damages only specific types of cells. Reversible Lesions (Inactivations): Method: Usecannulaeto temporarily inactivate brain regions by injecting drugs. ○ Example:Baclofen + Muscimol. Benefit: Allows forwithin-subjects designwithout permanent damage. Electrical Lesions: P roblem: Electricity is imprecise since neurons are electrical in nature → widespread unintended damage. Challenges with Lesion Studies: Timing of tests is critical: ○ Too soon: Confounding variables due to recovery effects. ○ Too late: Rats may fully recover due toneuroplasticity. Note: Rats can tolerate significant brain lesions and recover better than humans Optogenetics Mechanism: Light-gated ion channels (e.g.,Channelrhodopsinsfrom bacteria). Light exposure changes the protein shape, allowing ions to flow. Procedure: Requires agenetic modelto introduce the gene forlight-gated proteins. Usessystem-specific transcription factorsto target specific brain regions. Uses: R ecording/mapping neural circuits. Manipulating neural activity. Challenges: Backwards propagation can occur during optogenetic manipulations. Stains Golgi Stain Best for visualizingindividual neurons. Nissl Stain / Cresyl Violet Stain U sed to seecell bodies. Helps with visualizing regions in astereotaxic atlas. Fibre Stains(for white matter): Examples:Luxol-fast blue,Toluidine blue. Green Fluorescent Protein (GFP) ource: Fluorescent protein from jellyfish. S Application: Can be inserted into the genome or directlyinto cells. Function: Fluoresces when light is shone on neurons. Brainbow Mouse: Modified GFP to visualize neurons inmultiple colors Neuroimaging Static (Structural Imaging) P urpose: Captures a single point in time; does not show brain activity. Uses: Identifying structural differences (e.g., oldvs. young, rich vs. poor brains). Techniques: 1. Computerized Axial Tomography (CAT/CT) Uses multiple X-ray images from different angles to produce2D slices that are stacked into a3D image. Strengths: Good for identifyingtissue vs. fluid. Low radiation risk(compared to traditional X-rays). Improved by modern image processing software. Limitations: Cannot easily differentiatewhite matterfromgrey matter. Relatively low-resolution compared to MRI. Fun Fact: The Beatles' record company helped fund the original CT machines. 2. Magnetic Resonance Imaging (MRI) Relies on strong magnetic fields to image the brain. Process: A strong magnetic field alignshydrogen atomsin thebrain. A second magnetic pulse knocks atoms out of alignment. As atoms return to alignment (relaxation), they releaseenergy that is measured by the MRI. Strengths: Produceshigh-quality 3D imageswith better resolutionthan CT. No radiation risk. Limitations: Requires extremely low temperatures tomaintain the strong magnetic field. . Diffusion Tensor Imaging (DTI) 3 Avariant of MRIthat tracks the movement ofwatermoleculesin the brain. Water moves preferentiallyalong axons(white mattertracts). Strengths: Provides clear images ofwhite matter bundles(tracts). Useful for disorders related towhite matter dysfunction. Helps identify white matter differences across individuals or groups. 4. X-Ray Basic structural imaging. Mechanism: X-rays pass through tissue and are absorbedat varying rates, creating an image. Limitations: High radiation exposure → adverse health effects. Limited detail compared to CT or MRI. Dynamic (Functional Imaging) P urpose: Measuresbrain activityindirectly (not voltage changes). Techniques: 1. Positron Emission Tomography (PET) ○ Mechanism: Patient is injected with aradioactive tracertargetinga specific system (e.g., radioactive cocaine for the dopamine system). Brain activity is measured based on the distribution and concentration of the tracer. ○ Paired Image Subtraction: Two sessions: 1. Baseline(patient does nothing). 2. Task(patient performs an activity). Subtract baseline activity from stimulation activity to isolate specific task-related activation. ○ Strengths: Targets specific systems (e.g., dopamine). Useful for understanding gradual changes over time (e.g., age-related dopamine system decline). ○ Limitations: Very expensive: Requires fresh radioactive tracers(produced in a cyclotron→ ~$5k/hour per patient). Temporally slow: Poor time resolution. Poor spatial resolution. ○ Key Note: PET is useful for visualizing systems thatother methods cannot, such as neurotransmitter systems. 2. Functional MRI (fMRI) ○ Similar to MRI but measuresbrain activityby detectingchanges inblood oxygen levels(BOLD signal). ○ Strengths: Non-invasive (no radiation). High spatial resolution compared to PET. ○ Limitations: Temporally slower than EEG methods. . Resting-State Functional Connectivity MRI (rsfcMRI) 3 ○ Captures functional connections between brain regions while the subject is at rest. ○ Useful for identifying default brain network activity and connectivity patterns. Functional MRI (fMRI): The BOLD Response Concept: R elies on themagnetic propertiesof blood. Blood with oxygen has different magnetic properties than deoxygenated blood. Mechanism: B rain activity increases → Requires more oxygen →Blood Oxygen Level Dependent (BOLD) response. Hemodynamic response:Brain activity triggers blood vessel dilation (astrocyte-mediated) within ~6 seconds. Techniques: Paired Image Subtraction C ompare two similar tasks: baseline vs. experimental task. Subtract baseline to isolate activity of interest. Quality depends ongood controls. Event-Related Designs M any trials (e.g., 200 decision-making tasks) are averaged. Confounding variables: boredom, fatigue. Problems with Interpreting fMRI Results: . C 1 orrelative Nature: Does not show causation; measures brain activity indirectly. 2. Spatial Averaging: Results average out individualdifferences. 3. Spatial Resolution: ○ Good but limited. ○ ~13 million neurons fit within a cubic millimeter. 4. Temporal Resolution: ○ Slower than EEG. ○ ~6-second lag in the BOLD response. 5. Ambiguity: Shows activity but does not clarify itsspecific function. ○ E.g., Language activation may appear in both hemispheres. 6. Regional Hemodynamics: Slight timing differences acrossbrain regions can misalign results. 7. Confounds: Anxiety, boredom, sleep, drug use, or anticipatoryresponses. 8. Reliability: Every voxel is analyzed independently(statistical limitations). Resting-State Functional Connectivity MRI (rsfcMRI): M easures functional connections between brain regions at rest. Seed Region: Start with a brain region of interest(e.g., medial prefrontal cortex). Compare its activity with other regions. Functional Connectivity: Regions that show synchronized activity are considered functionally connected. Default Mode Network (DMN): Active during rest/mind-wandering. Includes: mPFC, PPC, PCC, hippocampus, lateral temporal cortex. Case Study: Heavy Metal Brain C ompared functional connectivity betweenheavy metal loversandclassical music lovers. Found differences in connectivity but: ○ No behavior was measured. ○ Researchers inferred behaviors, which may indicatebias. Type Examples Measures Strengths Limitations Structural CT, MRI, DTI tatic brain S igh-resolution H o functional N structure imaging (MRI/DTI) activity shown Functional P ET, fMRI, Indirect brain argets brain activity T emporally slow; T rsfcMRI activity (e.g., PET) costly (PET) asic B X-Ray issue T Simple imaging igh radiation; H X-Ray differences limited detail
