PSYC 304 Tools in Neuroscience Research Lecture Notes PDF

PSYC 304 Tools in neuroscience research Jay Hosking, PhD 1  Transcranial magnetic stimulation Usually to make “virtual lesions” Potential therapeutic applications https://www.youtube.com/watch?v=FMR_T0mM7Pc E...

PSYC 304 Tools in neuroscience research Jay Hosking, PhD 1  Transcranial magnetic stimulation Usually to make “virtual lesions” Potential therapeutic applications https://www.youtube.com/watch?v=FMR_T0mM7Pc Electrical activity 18 Deep thoughts by the rat Some examples: Morris water maze 5-choice serial reaction time task Conditioning (classical, operant) T-maze Animal models 19 BUT the quality of your model is determined by the quality of your behavioural assay A notable offender: the forced-swim test (FST) FST used to measure depression in the rodent, as well as antidepressant medication efficacy Difficulties in interpretation? Animal models 20 Why use animal models? Because they truly model Mammalian brain similarity Animal cognition is sophisticated https://www.youtube.com/watch?v=RRRISM23ABk Animal models 21  Drug “Challenge” Potential Routes – Intramuscular (IM) – Intravenous (IV) – Subcutaneous (SC) – Intraperitoneal (IP) Perhaps most common – Intraventricular Overcomes problems with drugs passing the blood-brain barrier – Multiple doses is best (e.g. saline only, then low, med, high) Within-subjects design Animal models 22  Invasive Electrical Recording Methods Four Invasive Electrophysiological Recording Methods – Intracellular Unit Recording – Extracellular Unit Recording – Multiple-Unit Recording – Invasive EEG Recording https://www.youtube.com/watch?v=1DJOTEDBA2c Animal models 23 Stereotaxic surgery For lesions, optogenetics, electrodes, more Employs stereotaxic atlas and instrument Allows accurate placement of lesions, probes, electrodes, etc. Reference point used is bregma Animal models 24 Lesion methods Chemical, i.e. excitotoxic lesions – e.g. quinolinic acid, ibotenic acid Selective chemical lesions – e.g. 6-hydroxydopamine (6-OHDA), 5,7-dihydroxytriptamine (5,7-DHT) Reversible lesions, aka inactivations – Cannulae – e.g. baclofen + muscimol – Benefit: within-subjects design! Interpretation of lesion studies Ideal post-surgery testing window? Unilateral vs. bilateral vs. contralateral lesions Animal models 25 Optogenetics Introducing: light-gated ion channels! – Channelrhodopsins Use system-specific transcription factors Can be used for both recording/mapping and manipulation Animal models 26  Reminder: stains are cool Golgi stain Nissl stain / cresyl violet stain Fibre stains – Luxol-fast blue (LFB) – Toluidine blue LFB stain Green fluorescent protein (GFP) – Many derivatives (e.g. YFP, BFP) – Can be inserted into living cells! e.g. Single-neuron electroporation Courtesy Dr. Kurt Haas Tectum neuron with GFP And much more! in awake animal! Imaging 27 Neuroimaging: structural and functional Static: AKA structural – Computerized axial tomography (CAT / CT) – Magnetic resonance imaging (MRI) – Diffusion tensor imaging (DTI) Dynamic: AKA functional – Positron emission tomography (PET) – Functional MRI (fMRI) – Resting-state functional connectivity MRI (rsfcMRI) Imaging 28  X-Ray X-ray tube, X-ray beam, film (or detectors) What can be seen? Structural imaging 29  Computed tomography (CT) The tube and detector Structural imaging 30  Computed tomography (CT) Rorden & Karnath, 2004 1977 1983 2004 Only as good as its algorithms Useful for? Structural imaging Drawbacks? 31  Computed Tomography (CT) Previously useful for stroke – Why? Structural imaging 32  Magnetic resonance imaging (MRI) https://www.youtube.com/watch?v=6BBx8BwLhqg Structural imaging 33 MRI Structural imaging 34  MRI Structural imaging 35 Diffusion Tensor Imaging (DTI) Variant of MRI Relies on how water molecules move in brain Useful for? Structural imaging 36 Positron Emission Tomography (PET) PET using radiolabelled cocaine (from Shumay et al., 2011) Functional imaging 37  PET Indirect measure (as is fMRI) – Meaning? Potential issues? Functional imaging 38  PET Paired image subtraction (similar for some fMRI) – Potential issues? Functional imaging 39  PET: less common now, but… Very expensive Temporally slow Poor spatial resolution BUT Useful for targeting specific systems (e.g. DA) Functional imaging 40 PET: dopamine D2 receptors decreased by addiction Functional imaging 41 Functional MRI (fMRI): the BOLD response Hemodynamic response Functional imaging 42 fMRI Imaging 43  fMRI: BOLD response Functional imaging 44 Paired Image Subtraction Functional imaging 45  Paired Image Subtraction The quality of your results depends on the quality of your controls! Functional imaging 46  Event-related fMRI Hosking et al. 2017 Huettel 2012, Common in fMRI these days adapted from Blamire et al. 1992 Allows you to avoid paired image subtraction Has many of its own challenges (e.g. boredom!) Functional imaging 47 Problems with interpreting fMRI studies? 1. Spatial averaging 2. Spatial resolution 3. Temporal resolution Voxel = 3D pixel 4. Not necessarily necessity 5. Focus on increases in activity Thinking critically 48 5. Focus on increases in activity: some regions are more active at rest than during task! The default mode network mPFC, posterior parietal cortex, PCC, hipp, lateral temporal cortex Resting state functional connectivity MRI Thinking critically 49  Problems with interpreting fMRI studies? 6. Regional hemodynamics 7. Confounds: anxiety, boredom 8. Drugs 9. Anticipatory hemodynamics 10. Reliability 11. Statistics Thinking critically 50 11. Statistics Thinking critically 51  The heavy metal brain? Poor assumptions? Multiple methods is critical Thinking critically 52  Choose wisely Which biopsychology method would you choose to study the following questions, and why? 1. Loss of grey matter in the weeks following a stroke 2. Changes in non-cortical brain activity following a stroke 3. Cortical activity while running on a treadmill 4. The external stimuli and situations in which a neuron fires 5. Changes in protein expression following a neurodegenerative disease (e.g. Alzheimer’s, CTE) 6. The role of the hippocampus in spatial learning and navigation. 7. Changes in decision making and motivation following acute and chronic drug use. 8. How we select words from our vocabulary for speaking. 9. The role of monoamine neurotransmitters in motivation. 10. What regions of the motor cortex control what parts of the body. “Assignment” 53