Color-Coded Big Ideas

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1 Big Ideas in Action: 1.02 Learning Objectives Color-Coded Big Ideas 1. The cells and tissues of nervous systems organize and interact using electrochemical signaling. SIGNALING. 2. Nervous systems are organized into a network of functional, interconnected subsystems. NETWORK. 3. Nervous systems enable organisms to perceive, interact with, and respond to their environment. INTERACTION. 4. Nervous systems grow and change over time. PLASTICITY. 5. Nervous systems experience biological and environmental insults which contribute to the pathology of neurological diseases. DISEASE. 6. Innovation of techniques to analyze nervous systems is integral to advancements in clinical, experimental, and theoretical neuroscience. DISCOVERY. Note: Learning Objectives marked with a preceding A are intended for Advanced Learners and include Advanced Content INTRODUCTION TO CELLULAR NEUROSCIENCE # OBJECTIVE ESSENTIAL QUESTIONS ESSENTIAL UNDERSTANDINGS GUIDANCE FOR TEACHERS 1 Students will be able to describe the role of neurons in the nervous system. - What is a neuron? - What role do neurons have in the nervous system? - A neuron is the basic working unit of the brain. - Neurons transmit electrochemical signals. - Three types of neurons include sensory neurons, motor neurons, and interneurons. - Although it is said that there are approximately 100 billion neurons in the human brain, show awareness that this is not a fact (closer to 86 billion). - Debunk the myth that we only use 10% of our brains.

2 2 Students will be able to identify and draw the different subcellular components of a neuron. - What are the major components of a neuron? - The dendrites receive signals from other neurons. - The cell body contains the nucleus and other organelles characteristic of all animal cells. - The axon allows for the transmission of signals. - The axon terminal is the site of neurotransmitter release. - It may be valuable to briefly mention the concept of axonal transport in order to show the interrelationships between the different subcellular compartments 3 Students will be able to compare and contrast the structure of neurons with other somatic cells. - What do neurons have in common with other somatic cells? - What makes a neuron unique? - Neurons contain the general set of organelles including the nucleus, mitochondria, and endoplasmic reticulum. - Neurons have many mitochondria which produce ATP for the active transport of ions. - Neurons have an extensive cytoskeleton to maintain its structure. 4 Students will be able to outline the relationship between structure and function of a neuron. - What is the relationship between structure and function in neurons? - The shape of a neuron allows for unidirectional transmission of an action potential. - The length of motor neurons allows signaling to limbs - The extensive arborization of Purkinje cells allows for signal integration. - If time permits, include a discussion of how these same principles relate to glia after the major glial cell types are introduced 5 Students will be able to explain the progression of the action potential and annotate graphs of their progression - How do neurons send signals from one end to the other? - Signals integrated at axon hillock - Sodium and Potassium channels allow the propagation of the action potential down an axon - Na+/K+ ATPase restores the resting potential to allow the axon to fire again - The rapid pace of these processes is important to survival - Note that if a neuron is stimulated in the middle, the action potential can be transmitted in both directions. However, this does not occur in physiological settings

3 - Graphs of the action potential reflect the distinct stages of ion channel opening - If time permits include an explanation of how Hodgkin and Huxley discovered the action potential 6 Students will be able to outline the role of the myelin sheath and saltatory conduction. - Why do neurons need a myelin sheath? - How do action potentials propagate? - The myelin sheath allows ions to diffuse to further parts of an axon much faster than they would without it. - At the Nodes of Ranvier, many Na+ channels are present to propagate the action potential. - If time permits, include a brief discussion of Multiple Sclerosis to underscore the role of the myelin sheath 7 Students will be able to explain the process of vesicle exocytosis - How are neurotransmitt ers released? - Neurotransmitters are contained in synaptic vesicles. - The action potential opens voltage-gated calcium ion channels. - Influx of calcium ions activate cytoplasmic proteins that mediate vesicle fusion. - Synaptic vesicles fuse with the presynaptic membrane and neurotransmitters are expelled. - Neurotransmitters diffuse through the synaptic cleft and bind to receptors on the postsynaptic membrane. 8 Students will be able to identify key neurotransmitte rs and their functions. - How do neurons signal to other neurons? - Glutamate is the brain s primary excitatory neurotransmitter and important in LTP - GABA is the brain s primary inhibitory neurotransmitter, Glycine is important in the PNS. - ACh is important at the NMJ - Dopamine is important for mediating reward and regulating motion. - Serotonin is important in regulating mood. - It may be best to explore two or three neurotransmitters in more depth and discuss their role in disease (e.g. dopamine in Parkinson s disease and Schizophrenia, Serotonin in depression

4 9 Students will be able to discuss the role of glial cells in the nervous system. - What other cells are in the brain? - Astrocytes - Microglia are a key component of the brain s immune defense - Oligodendrocytes - Schwann Cells A1 Students will be able to distinguish between Different morphological classes of neurons. - What are the different morphological classes of neurons? - Unipolar neurons - Pseudo-unipolar neurons - Bipolar neurons - Multipolar neurons - Anaxonic neurons - This concept is very difficult to understand without a diagram A2 Students will be able to describe axonal transport and its significance. - How are materials delivered to the axon terminal? - Motor proteins walk along microtubules to reach the axon terminal. - Organelles and vesicles are transported through axonal transport. -Poliovirus and Herpes Simplex Virus use retrograde transport to reach the cell bodies of infected cells. A3 Students will be able to outline the process by which neurotransmitte r signaling is stopped. - How are neurotransmitt ers removed from the synaptic cleft? - Neurotransmitters diffuse away from the synaptic cleft. - Enzymes in the synaptic cleft break down specific neurotransmitters. - Transport proteins in the presynaptic membrane actively transport neurotransmitters back into axon terminal. - One relevant example of the importance of understanding neurotransmitter breakdown is the use of AChE inhibitors in the treatment of Myasthenia Gravis, a neuromuscular disorder A4 Students will be able to describe the roles of other neurotransmitte rs in the nervous system. - What other signals do neurons use? - Histamine mediates itch sensation and inflammation. - Substance P transmits pain signals. - Orexin helps regulate the sleep/wake cycle. - Retrograde messengers, such as NO and CO, can signal to presynaptic neurons.

5 Paper Lab: Neurohistology Neurohistology Lab In this module, we learned about the cells that make up the nervous system. Now, it is your turn to analyze cells and determine their functions. Neurohistology refers to the study of the structure of the cells of the nervous system. From cells that look like little stars to cells that look like giant nets, our nervous system is home to a great variety of cellular morphology (shape). In the first part of the lab, we will investigate the relationship between the structure and function of neurons. In the second part, we will further investigate structure and function by proposing a structure well-suited to a particular function. Part I: Structure and Function (L) By Bechara Kachar - Public Domain, Shown here is a sensory cell with several stereocilia, or hairlike protrusions with a sensory function, extending from above it. What sorts of stimuli (e.g. mechanical, optic, chemical) would this cell best suited to detect? What sense(s) may they function in?

6 Photomicrograph of hematoxylin stained section of normal ependymal cells at 400x magnification. Human autopsy tissue. Image taken using an Olympus Microscope and Analysis-Imaging Software on by Martin Hasselblatt MD Shown above is a row of ependymal cells (in dark blue line near the middle). What might their functions be? What characteristics of the cell make you think this? Image retrieved from: Shown above are slices of the cerebral cortex of a normal human brain (L) and the brain of a patient with lissencephaly (R), a neurodevelopmental disorder. What differences can you see? How may these differences affect how the brain functions?

7 Part II: Predicting the Structure of Neurons The following descriptions are of important cells in the nervous system. Your job is to propose the structure of the cells in the nervous system. Be prepared to defend your answers in a discussion with your classmates. 1. Olfactory chemoreceptors must both detect chemical stimuli in the nose and transmit signals through the cribriform plate of the skull to reach the olfactory bulb, a structure just below the frontal lobe. Consider what adaptations may be necessary to maximize the amount of odorant detected, and what parts of the neuron (dendrites, axons) may be localized in the nose and inside the brain. 2. Motor neurons innervating smooth muscle need to stimulate large regions of muscle at once, meaning that a large number of synapses within a single cell is necessary. Hint: It is possible to have multiple synapses going along a single axon. What might the structure of neurons with these boutons en passant look like? What organelles would need to be in each of the boutons, or presynaptic terminals.

8 Advanced Paper Lab: Model Organisms Part A: Model Organisms in Research Below are abstracts from two research papers, with the names of the model organisms they studied removed. Based on your knowledge of the anatomy and physiology of key model organisms in neuroscience, identify the organism that was most likely studied in each of the following studies, and explain your reasoning. You should justify by underlining the relevant components of the abstract and writing a brief justification below it. Humanized Foxp2 accelerates learning by enhancing transitions from declarative to procedural performance The acquisition of language and speech is uniquely human, but how genetic changes might have adapted the nervous system to this capacity is not well understood. Two human-specific amino acid substitutions in the transcription factor forkhead box P2 (FOXP2) are outstanding mechanistic candidates, as they could have been positively selected during human evolution and as FOXP2 is the sole gene to date firmly linked to speech and language development. When these two substitutions are introduced into the endogenous Foxp2 gene of ( Foxp2 hum ), cortico-basal ganglia circuits are specifically affected. Here we demonstrate marked effects of this humanization of Foxp2 on learning and striatal neuroplasticity. Foxp2 hum/hum learn stimulus response associations faster than their WT [counterparts] in situations in which declarative (i.e., place-based) and procedural (i.e., response-based) forms of learning could compete during transitions toward proceduralization of action sequences. Striatal districts known to be differently related to these two modes of learning are affected differently in the Foxp2 hum/hum, as judged by measures of dopamine levels, gene expression patterns, and synaptic plasticity, including an NMDA receptor-dependent form of long-term depression. These findings raise the possibility that the humanized Foxp2 phenotype reflects a different tuning of corticostriatal systems involved in declarative and procedural learning, a capacity potentially contributing to adapting the human brain for speech and language acquisition. Reprogramming Chemotaxis Responses: Sensory Neurons Define Olfactory Preferences in Different olfactory cues elicit distinct behaviors such as attraction, avoidance, feeding, or mating. In the, these cues are sensed by a small number of olfactory neurons, each of which expresses several different odorant receptors. The type of behavioral response elicited by an odorant could be specified by the olfactory receptor or by the olfactory neuron in which the receptor is activated. The attractive odorant diacetyl is detected by the receptor protein ODR-10, which is normally expressed in the AWA olfactory neurons. The repulsive odorant 2-nonanone is detected by the AWB olfactory neurons. Transgenic animals that express ODR-10 in AWB rather than AWA avoid diacetyl, while maintaining qualitatively normal responses to other attractive and repulsive odorants. Animals that express ODR-10 simultaneously in AWA and AWB have a defective response to diacetyl, possibly because of conflicting olfactory inputs. Thus, an animal's preference for an odor is defined by the sensory neurons that express a given odorant receptor molecule.

9 Part B: Choosing the Right Organism Imagine that you are a neuroscientist in a lab trying to develop new technologies to advance the pace of research. Your job is to select the best model organism to conduct one of the three neurotechnology research projects listed below. Be sure to consider the evolutionary relationship of the organism to humans, the ease of handling and raising the organism, the ethical issues associated with research on vertebrates, and any other factors you find important. Explain your choice to your classmates in a two to three minute speech. 1. One promising approach to study the human connectome is the use of synaptic barcode sequencing. In barcode sequencing, each neuron is assigned a unique DNA barcode (approximately 20 nucleotides in length), and this sequence can be found in the neuron given the barcode and its immediate synaptic partners. By sequencing the barcodes from each neuron, researchers will be able to develop a better understanding of how neurons connect. Which model organism would be best in showing that barcode sequencing is a viable approach to studying the human connectome? 2. Although patch-clamping can give high-resolution imaging of single neurons, and EEG scans can show broad-scale connectivity, researchers currently lack the technology to characterize the activity of thousands of neurons at once. One promising approach is the use of genetically-encoded voltage indicators (GEVIs), which emit visual light upon depolarization. By using organisms with this gene incorporated into their genome, researchers will be able to image neural activity in situ (within the living organism in normal conditions). Which model organism would be best to study the properties of different GEVIs in living organisms? 3. Deep Brain Stimulation (DBS) surgery involves the surgical implantation of electrodes into the brain, and is commonly used to treat Parkinson s Disease (PD). However, it often involves side-effects on mood, so your research team is working to develop a DBS electrode that will not impact cognition in an animal model of PD. Which model organism would be best to use in a study investigating whether different DBS electrodes impact mood and other higher cognitive functions?