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Summary

This document is lecture notes on the structure and functions of the brain and various neurotransmitters. It includes information on brain chemistry and physiology, as well as the effects of various drugs. Learning objectives and summary sections are also included.

Full Transcript

Learn to support his slides in talking about it JAY lecture 2 Learning objectives (IMP FOR EXAMS) 1. Have a foundational understanding of basic brain facts. 2. Name and describe two general types of cells within the nervous system. 3. Identify three types of staining and the use case for each. 4....

Learn to support his slides in talking about it JAY lecture 2 Learning objectives (IMP FOR EXAMS) 1. Have a foundational understanding of basic brain facts. 2. Name and describe two general types of cells within the nervous system. 3. Identify three types of staining and the use case for each. 4. Name four types of glial cells and describe some functional roles for each. 5. Explain what is meant by a “tripartite synapse.” 6. Describe the central dogma of molecular biology. 7. Name and describe the function of some key cellular structures. In future, note how these relate to brain dysfunction! 8. Describe the relationship between dendrites and some common brain dysfunctions. 9. (Optional) Read the associated chapter, Pinel & Barnes Ch. 3, up to page 64. Human brain facts - 2-3% of body fat - Consumes 20% of your energy - 15% of blood is pumped to your brain - 20% of oxygen - 25% of glucose - Slightly larger in men than women - Huge individual variation - Hard to tell men vs women etc - Composed of neurons, glia (latin for glue; glue for the brain), stem cells (create new cells but not produce neurons in adulthood), blood vessel - motivation = manifesting drive to work for reward - Decrease motivation but not pleasure - Can be systemic or directly injected into VTA or NAcc DA and reward prediction error - Schultz et al - Pavlovian learning - Raster plot; shows brain activity throughout repeated trials - VTA (DA) neurons - After learning that light predicts reward (grape juice) - Neurons only fire for light, not reward - DA functioning dips when light is given, but not followed by juices - DA neurons are tracking animals expectations for reward - 3 conditions - … - DA neurons - Fire at first for unexpected reward - Shift their firing to stimuli thay predict reward - Go silent when predicted reward not delivered - Can be chained forward in time - Shapes future behaviors - Motivated to do things that reward you What does dopamine do? - Voluntary movement - Motivation - Learning as related to movement and motivation - Levels of arousal, attention, executive function Norepinephrine (aka noradrenaline) - Both a hormone and neurotransmitter - As NT, it originates in brain stem called locus coeruleus - Projects all the way across the brain esp cortex and cerebellum - 2 main receptor types with subtypes and sub-subtypes - All metabotropic - Modulatory effects - NE and epinephrine act similarly, on same receptors - Causes heterosynaptic facilitation - Makes you very awake - Baseline levels in wakefulness/arousal - Enhancement of memory by stress/emotion - Brain version of flight or fight - Acts to increase baseline levels of arousal and in stressful events - Evolutionary useful - Remembers dangerous indicators - Flashbulb memory driven by NE - NE also holds on to traumatic events - PTSD driven by high level of NE release - PSTD and propranolol - Norepinephrine antagonist aka beta blockers - Potential PTSD treatment via reconsolidation - Consolidation; working memory to long term memory - Reconsolidation; consolidate second time - Distort memory as it is flexible Propranolol - Give them beta blocker in therapy - Blocks stress arousal - Have them reexperience traumatic event - Talk about it again - This time they go through the story again but when remembering them is less intense as receptors are blocked - 1-3 months later remembering the event again is less intense but not forgetting memory - Hurts less - Reduced symptoms Ethics - PTSD is sensitive and disruptive - Given to soldiers - Not used in therapy; why? - … - Side effects - Bad for underlying heart conditions Serotonin - Originates from the raphe nuclei (brain stem) - Projects all over brain esp cortex, thalamus, cerebellum - 15 receptor types, almost all metabotropic - Precursor; tryptophan - Serotonin depletion effects - Participants in lab - 2 conditions: normal food vs food without tryptophan - Indirectly reduce serotonin levels - Low serotonin impacts performance on tasks like stroop task - Low cognitive flexibility - Increases aggression - But does not show decrease in mood - Family history of depression - … - Not exactly a mood molecule Selective serotonin reuptake inhibitors - SSRIs eg Prozac - For depression, anxiety, OCD - Chemical imbalance theory of depression - Not the best framework - History of monoamines implicated in mood disorders - … - Block serotonin from being removed from the synapse - Block transporters and prevent uptake into the axon - Agonist effect but not an agonist - Effects of SSRIs quic, improvements slow - 2-4 weeks SSRI efficacy - Studies on SSRI show only subset of results - 75% of all SSRI studies were never published - Limits ability to make sense of data - Now, its better - SSRIs were effective or no? - Meta analyses: SSRIs no better than placebo for mild to moderate depression - For severe depression; shows a bit more of helpfulness - Modern SSRI data - Shows effectiveness but small effect size - Significantly help with depression but small effect size - … - Side effects - Changes in sex, eating, sleeping Hallucinogens - Psychedelics like LSD, DMT, psilocybin, etc are serotonin receptor agonists - Radical changes to our conscious perception and thoughts, minimal effects on mood (implication?) - Vastly increasing serotonin levels but not mood - Recent exam of psychedelics therapeutic value: end of life care, PTSD, addiction, and more - Not addicitve - Use of psychedelics in therapy Acetycholine - Other small NT - First discovered NT - Neuromuscular junction - Also basal forebrain - Wakefulness, attention, etc. - Nicotine” acetylcholine agonist - Too much of it makes stomach uneasy Endocannabinoids - Other small NT - 2 NTs, 2 receptors (both GPCRs) - Travel from dendrite to axon i.e. retrograde transmission - Good at passing through membranes - Weaken connection between 2 cells at a synapse - THC is a cannabinoid agonist Adenosine - Byproduct of ATP - Atp is cellular energy - All cells have adenosine receptors - Metabotropic - Largely inhibitory - Building up of daytime sleepiness - caffeine/theophyline - Caffeine is adenosine antagonist - Blocks adenosine receptors Endogenous opioids - Large molecule NT - Peptides - Proteins - Relief of pain = analgesia - endorphins - GPCRs - Metabotropic - Largely inhibitory - Highly addictive - Can cause intense euphoria - Increase baseline pleasure - Many NTs and receptors types/subtypes - The NT system that exogenous opioids (eg heroin, morphine, percocets) mimic - Fentanyl - Opiod deaths are catastrophe - Agonist - of what? - To counteract; opiod antagonist; naloxone - Receptors found in spinal cord, periaqueductal grey area, nucleus accumbens Neuroimaging (structural and functional) - Learning objectives 1. Describe the fundamental difference between structural and functional neuroimaging. What sorts of research questions can be addressed with structural neuroimaging? What sorts of research questions can be addressed with functional neuroimaging? 2. Describe and compare the different methods of structural brain imaging that are listed in this lecture. 3. Explain how an MRI machine works. 4. Describe and compare the different methods of functional brain imaging that are listed in this lecture. 5. Explain how PET and fMRI work. 6. In a single sentence, be able to discuss each of the many challenges involved in interpreting functional brain imaging data. 7. (Required) Read the paper by Owen (2014) posted on the main course page. It is a pop- science article, so I expect you to understand all of the material. Critically, though: Identify and describe the patient population in this article. Describe the methodological approach by Owen to solve these patients’ dilemma. Describe the results of these studies. Structural imaging - No time component - No activity overtime - Status image of body - Devoid of ongoing activity or changes in body - X-ray - Xray tube, xray beam, film (or detectors) - Rays passed through humans, absorbed by issues (more by some, less by others), hits a screen? - Cerebral angiography - I.e. an angiogram, - Contract x ray technique - Iodine - as an xray passed through, allows for a very vivid image of circular system in the brain (blood vessel map in brain) - Cannot see brain but solely the vessels - Useful for blood blockages in brain (shows blockage related stroke) - Also can see bleeding into the brain from another artery - Computed tomography (CT) - Weaker x ray - Hits many angles - Richer picture of what is inside our body - Overcomes limitations of traditional x ray - ‘Reconstruction’ - Use a computer to take all the 2D images and reconstruct into 3D model for eg for the brain - Useful to show difference between tissue and fluid - Can see stroke as image shows darker part of brain - Darker part = more CSF aka fluid in brain due to stroke - Can show hydrocephalus - Limitations - Cannot distinguish white vs grey matter in the issue - Cant show tumour in brain - Cant see worm in brain - MRI magnetic resonance imaging - Not x ray (like CT) - Uses magnetic fields instead of x ray - Hydrogen atoms align with NS poles of strong magnetic field - Why are metals so scary in MRI - Metals inside your body or on you (jewelry) would find ways to leave your body and attach to the MRI machine - Useful - Non invasive - Shows white and grey matter - Detailed image - Step 1; align all protons with the large magnetic fields - Step 2; momentarily perturb that alignment with a second varying magnetic field - Step 3; measure radiofrequency signal produced during realignment with the large magnetic field - Hydrogen ‘relaxation’ in brain - Example of an overlay plot - Advantage over traditional lesion studies - Overlapping brain damage is associated with overlapping symptoms - Diffuison tensor imaging (DTI) - variant of MRI - Hydrogen all over brain from water - Relies on how water molecules move in brain - Movement in random in extracellular fluid - Movement in cell body aka axon is random but constrained to along the axon - Measuring random movement - Thus, we get picture of where we have axons in the brain - Picks up on white matter tracts - Useful - Autism spectrum; different white matter tracts - Aphasia - Adrian Owen’s paper Functional imaging - EEG - True direct measure of activity in NS is voltage - Produces waves - Frequency of waves = activity in brain - Aka higher frequency, more action potentials - Amplitude = the synchrony of neuron action potentials - Low amplitude = neurons are firing at different times - During non-REM sleep, neurons fire at same time - High amplitude Positron emission tomography (PET) - Radioactive cocaine - You can see map of whatever cocaine is acting on, aka, dopamine system - Image shows basal ganglia - Indirect measure (fMRI) - Can use radioactive water or glucose - Make molecule radioactive using cyclotron - Problem with radioactive molecule is that they decay - EXPENSIVE - Potential issues of INdirect measure of activity? - … - Mean difference images - Stimulation condition - control condition = difference image that shows meaningful activity for relevant area? - watch video - Take all individual difference images - Create a mean difference image

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