Brain and Cognitive Sciences at MIT Course 9.17: Systems Neuroscience Laboratory Welcome to 9.17 ! 1 Course 9.17: Systems Neuroscience Laboratory, Brain and Cognitive Sciences 1 Image courtesy of EMSL on Flickr. CC BY-NC-SA. • 100 billion computing elements • solves problems not soluble by any previous machine • requires only 20 watts of power! Course 9.02: Keyand algorithms are still classified Systems Neuroscience Laboratory, Brain Cognitive Sciences 2 2 Class 1: overview • • • • Goals, syllabus, grading, expectations, etc. Overview of methods used to study the brain Discussion on animals in research Lab tour and safety discussion Course 9.17: Systems Neuroscience Laboratory, Brain and Cognitive Sciences 3 Class 1: overview • • • • Goals, syllabus, grading, expectations, etc. Overview of methods used to study the brain Discussion on animals in research Lab tour and safety discussion Course 9.17: Systems Neuroscience Laboratory, Brain and Cognitive Sciences 4 Expectations What you should expect of us: What we expect of you: • • • • • • • • • • Prepared to teach topic Eager to help with techniques Eager to answer questions Available outside of class Feedback on your work Be prepared for each lab Eager to learn techniques Ask questions! Seek help! Work submitted on time Course 9.17: Systems Neuroscience Laboratory, Brain and Cognitive Sciences 5 Adding and dropping 9.17 Adding 9.17: Students on the wait list that attend the first week will have priority if a spot becomes available by the start of week 2. No adds will be allowed after the end of week 2, and week 2 quizzes and attendance will count in the final grade for ALL students. Dropping 9.17: We understand that you may decide to drop the course for any reason. However, because space is limited we kindly ask that you let Susan Lanza in the BCS office know of your drop by the start of week 2. If you do not do this or decide to drop the course at a later date, you may get on the wait list for the course in a future year, but first-time entrants on the wait list will get priority. Listener status for 9.17: Listener status is currently not allowed in 9.17. Course 9.02: Systems Neuroscience Laboratory, Brain and Cognitive Sciences 6 Brain and Cognitive Sciences at MIT Course 9.17: Systems Neuroscience Laboratory Documents you have been given today: 9.17 Lab handbook (Lab Manual) Your 9.17 Lab notebook (empty) Course 9.02: Systems Neuroscience Laboratory, Brain and Cognitive Sciences 7 Brain and Cognitive Sciences at MIT Course 9.17: Systems Neuroscience Laboratory Components of your 9.17 grade: - quizzes (11) -- only best 10 will count - lab reports (2) - lab notebook (11) -- only best 10 will count - Matlab tutorials - in-lab participation - in-recitation participation Course 9.02: Systems Neuroscience Laboratory, Brain and Cognitive Sciences 8 Brain and Cognitive Sciences at MIT Course 9.17: Systems Neuroscience Laboratory Each week: Monday lecture: background on lab Tues recitation: prepare by reading one paper Wed laboratory: prepare by reading protocol, background readings, prepare your lab notebook Quiz given at start of each lab *: - lecture material - recitation papers and questions - lab preparation material ( * there are 11 quizzes, but you get to throw one out! ) Course 9.02: Systems Neuroscience Laboratory, Brain and Cognitive Sciences 9 Brain and Cognitive Sciences at MIT Course 9.17: Systems Neuroscience Laboratory Lab reports: - You will learn how to write a short scientific paper. - A description of what is expected and how we will provide feedback and grading of y our lab reports is on the class web site. - Because you will typically work in teams of 2-3 in each lab, the data in each lab report will often be identical. However, W E EXPECT EACH OF YOU TO WRITE YOUR OWN LAB REPORT. Duplicate sentences or paragraphs in lab reports are considered to be a form a plagiarism and, as MIT students, you already know that this is extremely unethical. If t his, or a ny other form of plagiarism (e.g. sentences copied from references without citation) is apparent in y our lab report, the report will receive a grade of zero, and you may be referred to the MIT Committee on Discipline. The primary grading criteria for the lab reports are: 1) Proper organization (Is the proper material in the proper section?) 2) Clarity (Are the key points obvious? Is it easy to read and understand?) 3) Conciseness (Are there wasted sentences? Too much redundancy?) 4) Quality of data and figures (Are data figures appropriate and clear?) Detailed grading criteria will be posted online and you will receive Course 9.02: Systems Neuroscience and Cognitive Sciences feedback from us on Laboratory, first labBrain report (chance to revise). 10 Brain and Cognitive Sciences at MIT Course 9.17: Systems Neuroscience Laboratory Lab notebook: •Goal is to teach you how do document your experimental work 1. Outline protocol for lab BEFORE your lab session (you will be asked to leave the lab until your notebook shows your experimental plan) 2. Make all notes, data, and drawings regarding your lab in your notebook 3. Turn in a copy of your lab notebook pages for the lab when you leave the lab. Course 9.02: Systems Neuroscience Laboratory, Brain and Cognitive Sciences 11 Brain and Cognitive Sciences at MIT Course 9.17: Systems Neuroscience Laboratory 9.17 Handbook: - Overall course grade. - quizzes, lab reports (2), in-lab participation, Matlab tutorials, recitation participation, lab notebook - FAQs: missed / late policies, office hours, etc. - Lots of advice and guidance on how to prepare your lab reports, etc. Course 9.02: Systems Neuroscience Laboratory, Brain and Cognitive Sciences 12 ! Brain and Cognitive Sciences at MIT ! Course 9.17: Systems ! Neuroscience Laboratory ! Final grade sheet (in 9.17 handbook) ! ! ! ! Student: Section: Primary TA: Total 9.17 points: Max 9.17 points: Final letter grade: Jane Doe Wed TA name 0 (Sum 1000 >900 = A, >800 = B, >700 = C, >600 = D Quizzes- Best 10 of 11 No. 1 2 3 4 5 6 7 8 9 10 11 Topic Lab Notebook - Best 10 of 11 Points of Max 30 30 30 30 30 30 30 30 30 30 30 Practical Lab (both) C. Anatomy (Tye) Cockroach (Tye) Frog (DiCarlo) Rat Phys. (Tye) Rat Phys. (Tye) Matlab (DiCarlo) Fly (DiCarlo) Fly (DiCarlo) Fly (DiCarlo) Fly (DiCarlo) Total quiz points: 0 300 Matlab projects No. 0 1 2 3 Topic Plotting Spike detection Movie creation Data analysis of six boxes below) No. Topic 1 2 3 4 5 6 7 8 9 10 11 Points of Max 10 10 10 10 10 10 10 10 10 10 10 Practical Lab Classic Anatomy Cockroach Frog Rat Physiology Rat Physiology Fly Wet Lab I Fly Movie Design Fly Wet Lab II Fly Data Analysis EEG/MRI Total notebook points: 0 100 Research reports Points of Max 10 20 30 40 No. Topic 1 Rat Phyisology 2 Fly Vision Points Total report points: of Max 200 200 0 400 Free extension used?: ! ! Total Matlab points: 0 100 Lab participation Recitation Participation No. Topic 1 Recitation Total particip. points: No. Points of Max 40 0 ! Course 9.02: Systems Neuroscience Laboratory, Brain and Cognitive Sciences ! 40 1 2 3 4 Topic Anatomy General Phys. Barrel Phys. Fly Vision Total particip. points: Points of Max 15 15 15 15 0 60 Class 1: overview • • • • Goals, syllabus, grading, expectations, etc. Overview of methods used to study the brain Discussion on animals in research Lab tour and safety discussion Course 9.17: Systems Neuroscience Laboratory, Brain and Cognitive Sciences 14 Genes and molecules Cellular components Neurons Interaction of many neurons Behavior Introduction The fundamental goal of neuroscience is to understand the brain mechanisms that give rise to behavior “Consciousness” “Theory of mind” “Understanding causality” “Reasoning” “Learning” “Emotion” “Motivation” “Language” “Memory” “Decision making” “Perception” “Recognition” Course 9.17: Systems Neuroscience Laboratory, Brain and Cognitive Sciences “Intent” “Action” 15 Scene “understanding” Car Person Building Tree Sign Lamp post ... Courtesy of Tomaso A. Poggio. Used with permission. From MIT Street Scenes Database (Courtesy of Tommy Poggio) 16 Serial snapshot analysis scene “understanding” Courtesy of Tomaso A. Poggio. Used with permission. 17 Serial snapshot analysis scene “understanding” Courtesy of Tomaso A. Poggio. Used with permission. From “Street Scenes” Database (Courtesy of Tommy Poggio) 18 scene “understanding” Serial snapshot analysis Snapshot (core) object detection • • • • • Fast (~200 msec) Feels effortless Large number of objects No pre-cueing needed Tolerant to variation Our mission: Understand how the brain constructs a neuronal representation that underlies core object detection 19 The ventral visual processing stream Dorsal visual stream Decision and action Memory Ventral visual stream Motter, BC, and VB Mountcastle. "The Functional Properties of the Light-Sensitive Neurons of the Posterior Parietal Cortex Studied in Waking Monkeys: Foveal Sparing and Opponent Vector Organization." The Journal of Neuroscience Courtesy of Elsevier, Inc., http://www.sciencedirect.com. Used with permission. 1, no. 1 (1981): 3-26. Available under Creative Commons BY-NC-SA. Houses critical circuits and resulting neuronal representations for object recognition. We can study those representations at the level of neuronal spikes. 20 The ventral visual processing stream Ventral visual stream Courtesy of Elsevier, Inc., http://www.sciencedirect.com. Used with permission. 21 The ventral visual processing stream Ventral visual stream Courtesy of Elsevier, Inc., http://www.sciencedirect.com. Used with permission. Image: Kimberly Brown-Azzarello. Flickr. CC BY-NC. 22 The ventral visual processing stream Ventral visual stream Courtesy of Elsevier, Inc., http://www.sciencedirect.com. Used with permission. Image: Kimberly Brown-Azzarello. Flickr. CC BY-NC. 23 The ventral visual processing stream Ventral visual stream Courtesy of Elsevier, Inc., http://www.sciencedirect.com. Used with permission. Image: Kimberly Brown-Azzarello. Flickr. CC BY-NC. Key cortical algorithms are unknown; remarkable potential 24 Our primary tools: Behavior Physiology Computation L3 thresh/sat Learning Rate Trace “Temp. Adv.” “Auto-reset” ... number of filters thresh/sat norm strength Learning normalization neighborhood kernel size n. of filters L1 Intervention norm strength normalization neighborhood L2 Imaging thresh/sat norm strength Rate Trace “Temp. Adv.” “Auto-reset” ... Learning normalization neighborhood kernel size Rate Trace “Temp. Adv.” “Auto-reset” ... number of filters input kernel size Collage images © source unknown. All rights reserved. This content is excluded from our Creative Commons license. For more information, see http://ocw.mit.edu/fairuse. . Image: Kimberly Brown-Azzarello. Flickr. CC BY-NC. 25 Emotion: the basis of motivated behavior • Emotions = evaluation of environment Motivation = response to environment (Kuhl, 1986) • Emotions provide a system to evaluate environmental stimuli and motivate a behavioral response (D’Amasio, 1994; Tooby & Cosmides, 1990) • Amygdala critical for assigning motivational significance to environmental stimuli (Brown & Schafer 1888; Kluver & Bucy, 1937) • Amygdala evolutionarily conserved; dubbed “reptilian brain (Maclean, 1969) 26 Neural basis of motivated behavior DAPI BLA CeM EYFP Figure'1,'Tye'et'al. CeL CeM BLA CeL h g on *** Total'Time in'Center'(s) off off 0 ChR2:BLA'Soma'(n=7) on *** ** 50 100 light'on light'on light'off light'on light'off light'off off on 0 off *** EYFP:BLA9CeA'(n=9) 0.07386 20 0.1764 0.1530 N/A 30 0 0 40 0.3216 0.0433 0 50 100 150 ChR2:BLA9CeA'(n=8) R off Extinction resistance 50 *** ChR2:'BLA'Somata'(n=7) Reinforcement omission (n ! 32/330; 10%) r2 p Extinction only (n ! 47/330; 14%) r2 p Maint. only (n ! 4/330; 1%) Empty in Maint. (n ! 17/330; 5%) r2 200 EYFP:'BLA9CeA'(n=9) ChR2:'BLA9CeA'(n=8) 250 708.1'cm c open light'off b 0.5 630.3'cm light'on 15'min 1 Probability'of' Open'Arm'Entry 838.2'cm light'off Bare'fiber over'BLA Beveled cannula over'CeA Population Time'in'Open'Arm'(s)' Behavior Beveled cannula over'CeA Figure 8. A subpopulation of BLA neurons that encoded port entries in the presence predicts response intensity and extinction resistance. A, A representative BLA neuron t absent during maintenance, but developed a phasic inhibition upon port entries when s condition including the 22 neurons that displayed a similar response profile to that of t is present, did not respond upon port entries when sucrose was absent during maintena showing normalized activity in each port entry condition for neurons with response prof recorded per rat was significantly correlated with each rat’s response intensity (E) and 0 0 N in'Center'(s) ChR2:BLA9CeA 18'min Table 2. Linear regression scores and p values for correlations between all ne closed a Circuit 3'min EYFP:BLA9CeA ChR2:BLA'Soma ChR2:BLA9CeA What neural circuits mediate motivated behaviors? What processes underlie motivated behavior? Cell EYFP:BLA9CeA How do different cell types contribute to distinct aspects of behavior? 124 • J. Neurosci., January 6, 2010 • 30(1):116 –125 2:'BLA'Soma How can the balance of synaptic input influence behavior? Synapse 27 0 Why do we care about emotion and motivation? Anxiety Positive Emotion Motivated to Seek Rewards Negative Emotion Motivated to Avoid Punishment Addiction Depression 28 Genes and molecules Cellular components Neurons Interaction of many neurons Behavior Introduction The fundamental goal of neuroscience is to understand the brain mechanisms that give rise to behavior “Consciousness” “Theory of mind” “Understanding causality” “Reasoning” “Learning” “Emotion” “Motivation” “Language” “Memory” “Decision making” “Perception” “Recognition” Course 9.17: Systems Neuroscience Laboratory, Brain and Cognitive Sciences “Intent” “Action” 29 Genes and molecules Cellular components Neurons Level Functions investigated Preparations Techniques Molecular neuroscience - Channel function - Signaling cascades - Neurotransmitter processing - Modifications to above: (development, memory) -DNA solutions -Protein solutions -Cell fractions -Cell cultures - Brain slices - transgenic animals* - Xray crystallography - DNA and protein sequence analysis - in situ hybridization - genetic manipulations -models / computation - neurotransimission - signal integration - neuronal plasticity - neuronal development - Cell cultures - Isolated nerve - Brain slices - detailed, simulated neurons - transgenic animals* - electron microscopy - chemical manipulations - intra-cellular electrophysiology - immunohistochemistry - two-photon microscopy -models / computation - system architecture - system connectivity - neuronal signaling - neuronal transfer functions - neuronal coding of information - neuronal computation - links between neuronal properties and behavior - Brain slices - invertebrates - anesthetized vertebrates - awake vertebrates - awake,non-human primates - simulated neuronal networks - transgenic animals* - gross anatomy, histology - immunohistochemistry - tract tracing - extra-cellular electrophysiology - intra-cellular electrophysiology - multi-unit electrophysiology - chronic electrophysiology - electrical microstimulation - pharmacological stimulation/inhibition - brain lesions - intrinsic signal imaging - animal behavior and psychophysics - models / computation - Perception - Motor control - Memory - Decision/reasoning - Language - Consciousness? - human subjects - simulated brain processes - human psychophysics - behavioral observations - functional MRI -models / computation (DNA, proteins, transmitters) Cellular neuroscience (whole neurons) Systems neuroscience (interactions of groups of neurons) Interaction of many neurons Cognitive neuroscience Behavior (emergent, complex behavior) Course 9.17: Systems Neuroscience Laboratory, Brain and Cognitive Sciences 30 Level Functions investigated Preparations Techniques Systems neuroscience - system architecture - system connectivity - neuronal signaling - neuronal transfer functions - neuronal coding of information - neuronal computation - links between neuronal properties and behavior - Brain slices - invertebrates - anesthetized vertebrates - awake vertebrates - awake,non-human primates - simulated neuronal networks - transgenic animals* - gross anatomy, histology - immunohistochemistry - tract tracing - extra-cellular electrophysiology - intra-cellular electrophysiology - multi-unit electrophysiology - chronic electrophysiology - electrical microstimulation - pharmacological stimulation/inhibition - brain lesions - intrinsic signal imaging - animal behavior and psychophysics - models / computation (interactions of groups of neurons) Course 9.17: Systems Neuroscience Laboratory, Brain and Cognitive Sciences 31 What is the right tool for the job? Behavior (psychophysics) Brain 3 2 Map 1 Column 0 Layer Neuron Dendrite Synapse MEG + ERP 2-Deoxglucose Spatial resolution (log mm) Spatial and temporal resolution fMRI Optical imaging PET Gross anatomy Lesions -1 -2 -3 Extracellular electrophysiology Patch clamp electrophysiology Light Microscopy -4 -3 -2 Milisecond -1 0 Second 1 2 3 4 Minute Hour 5 6 7 Day Temporal resolution (log seconds) Image by MIT OpenCourseWare. Course 9.02: Systems Neuroscience Laboratory, Brain and Cognitive Sciences 32 Use of animals in this class: f animals • It is not possible to study the nervous system without handling actual neural tissue. Thus, several of the classes will use animals (rats, frogs, cockroaches, flies). • We have made every attempt to reduce the number of animals used in this course. Several labs use simulations instead of animals. • All animal procedures are in accordance with NIH guidelines are approved by MIT’s Committee on Animal Care. • We will have a presentation on the use on animals in research and teaching from an MIT veterinarian. • If you are uncomfortable with the use of animals, please contact one of us immediately after this introduction (TODAY). Course 9.17: Systems Neuroscience Laboratory, Brain and Cognitive Sciences 33 Class 1: overview • • • • Goals, syllabus, grading, expectations, etc. Overview of methods used to study the brain Discussion on animals in research Lab tour and safety presentation • (Add/drop/etc. Please put your name on sign up sheet before you leave. See Steve Russo for this!) Course 9.17: Systems Neuroscience Laboratory, Brain and Cognitive Sciences 34 MIT OpenCourseWare http://ocw.mit.edu 9.17 Systems Neuroscience Lab Spring 2013 For information about citing these materials or our Terms of Use, visit: http://ocw.mit.edu/terms.