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Lesson 4.1: Engage: What is sleep? Rationale: This lesson is intended to introduce students to the concept of sleep and how we can visualize it to describe it. The lesson sets the students up to begin to learn about sleep in the context of neuronal control, a logical progression from the previous unit that focused on simple pathways. Here we will now continue to explore the role of stimulation and inhibition in complex circuits. Activities: Students begin the lesson by taking a sleep quiz. The purpose of the sleep quiz is to uncover misconceptions about the role of sleep and what we know about sleep. The sleep quiz is used as a springboard to take students interactively through basic information about sleep. Additionally, this lesson introduces the EEG because researchers use this tool to analyze sleep. With a partner, students complete a worksheet to analyze an EEG. The class concludes with a short discussion of how much sleep is enough. Homework: Bring in sleep journal for tomorrow’s lesson. Lesson Plan Do Now (5 min): The students work with a partner to determine whether four statements are true or false. Socratic Discussion (15 minutes): The sleep quiz is used to drive the student discussion about what we know about sleep, how it is measured and sleep characteristics. Activity (10 minutes): Analysis of an EEG Wrap-up (10 minutes): What amount of sleep is enough? Homework: Bring in sleep journal for tomorrow’s lesson. Do now: Have the students work with a partner to determine if the four statements are true or false. After giving the students 5 minutes to complete this task, review the answers with them using the next set of slides. Discussion: Ask the students – is the first statement “You will die if you don’t get enough sleep.” True or False? True (by extrapolation). Rats who are deprived of sleep die within a couple of weeks. This is because their homeostatic mechanisms (that control physiological processes) are linked to the sleep-wake cycle. The human record for going without sleep is 12 days. Show the students that when they are deprived other basic needs (air, water, food) as well as sleep, the result is death. Ask the students – is the second statement “You sleep so your body can repair itself from the day’s activities” True or False? False. Most people think that sleep is a time to recharge their batteries however there’s no evidence that more repair occurs during sleep than during rest or relaxed wakefulness. Ask the students – is the third statement “You can’t perform properly if you don’t get enough sleep.” True or False? True. Being sleep deprived impairs performance to the same extent as being drunk. We will revisit the concept of sleep deprivation in the next lesson, through the analysis of the students’ sleep journals, so you might want to stress this idea of sleep deprivation having an equally powerful effect on performance now. Ask the students – is the fourth statement “When you sleep your brain is less active than when you’re awake.” True or False? False. Your brain is incredibly active during sleep. Brain activity during sleep is the focus of the remainder of this lesson. You can measure the brain’s activity during sleep with an EEG. Ask the students – has anyone had an EEG before? If so, have that student describe what was done to record the EEG. If not, describe for the class how an EEG is recorded. A cap is placed on the head that has electrodes in it spaced out at regular intervals over the whole of the cortex. The EEG then records the voltage flowing through the brain tissue between each pair of electrodes. Because each pair of electrodes samples the activity of a population of neurons in different brain regions, each of the individual EEG traces will be different. Draw the students’ attention to the coding of the different electrodes placed on the scalp. At the front of the head the electrodes are coded with the letter “F” and at the back of the brain the electrodes are coded with the letter “O”. Ask the students if they can figure out the coding system. The coding system is for the lobe that the electrode is recording from: F – Frontal lobe involved in planning P – Parietal lobe involved in sensory processing T –Temporal lobe involved in auditory processing O – Occipital lobe involved in visual processing C – Motor in this case involved in motor control Tell the students that even numbers are placed on the left hand side and odd numbers are place on the right hand side. The EEG measures activity between electrodes Use this slide to show the students what the data from an EEG looks like. Draw the students’ attention to the coding system for each electrode on the trace. Tell the students that the electrodes measure the electrical activity between the two coded electrodes, which is why each trace is reported as P3 – T5. The EEG records activity in the form of waves Ask the students – When talking about a wave, what is frequency? What is amplitude? Frequency refers to how long (length) a wave is from trough to trough. Amplitude refers to how large (height) the wave is from peak to peak. Animate the slide to show the students that the red arrow labeled “A” refers to amplitude, and the blue arrow labeled “B” refers to frequency. What do the brainwaves signify? Use this slide to discuss how the EEG varies given our state of consciousness. First, make sure that the students are able to determine traces with high and low frequency, as well as traces of high and low amplitude. Ask the students to point out areas of high amplitude low frequency, high amplitude high frequency, low amplitude low frequency and low amplitude high frequency. Explain to the students we don’t really know how this translates into brain function i.e. none of the waves is equivalent to anything like a thought or a memory, they’re just showing overall activity in those areas. Next, introduce the students to the concept that our brain waves differ given our state of consciousness. Show the students that when we are mentally alert with our eyes open, our EEGs have high frequency, low amplitude waves. Show the students that when we are drowsy or asleep, our EEGs have lower frequency with higher amplitude waves. Activity: Give each student a copy of Neuro Unit 4.1 EEG Worksheet and have them work with a partner to complete the worksheet. (The worksheet can be found in the materials folder for this lesson entitled: Neuro Unit 4.1 EEG worksheet) Make sure that the students understand that the EEG measures activity between two cortical areas. Emphasize that the measurement is overall activity through many thousands of neurons. After giving the students 7-10 minutes to complete this task, review potential answers with them using the animations in this slide. Show the students that circle A represents an area of high frequency. Then ask the students, what leads/what area of the brain does this trace represent? P3-O1 Show the students that circle B represents an area of low frequency. Then ask the students, what leads/what area of the brain does this trace represent? Fp1-F3 Show the students that circle C represents an area of high amplitude. Then ask the students, what leads/what area of the brain does this trace represent? Fp2-F8 Show the students that circle D represents an area of low amplitude. Then ask the students, what leads/what area of the brain does this trace represent? T3-T5 Show the students that circle E represents an area of high frequency and amplitude. Then ask the students, what leads/what area of the brain does this trace represent? CZ-PZ The EEG detects multiple stages of sleep Use this slide to describe how the EEG changes as we progress through a night’s sleep. Show the students that the awake EEG is characterized by high frequency, low amplitude waves, which slowly decrease in frequency and increase in amplitude. That is, until we get to Stage 5, which again has an EEG with high frequency and low amplitude waves. Ask the students – can anyone guess what is happening during this sleep stage that would cause the brain to have an EEG that is similar to the awake brain? Rapid eye movement (REM) sleep which is the stage of sleep that we dream. Animate the slide to show the students that there are essentially two sleep stages – Non rapid eye movement (NREM) and rapid eye movement (REM). Use the next slide to further discuss the two types of sleep. Two types of sleep Ask the students – What is the difference between NREM and REM sleep? NREM sleep in which the sleeper is still and the eyes aren’t moving. If the sleeper is woken up in this stage they rarely describe dreams. REM sleep is the physiologically dynamic stage. The overall physiology is active and the eyes move rapidly. If the sleeper is woken up at this stage they commonly report dreams (although they may forget them shortly thereafter). Wrap Up: How much is enough sleep? Use this slide to get students thinking about how much sleep is needed to function properly. Show the students different animals sleep for drastically different amounts of time. Remind the students that they should be keeping track of their own sleeping habits using their sleep journal, and that their homework for tonight is to make sure to bring that with them to class tomorrow since we will be analyzing it as a whole class. Homework: A week ago (in Neuro Unit 3.1), students were assigned to complete a sleep journal which can be found in the materials folder of Neuro Unit 3.1 or Neuro Unit 4.2, entitled: Neuro Unit Sleep Journal. Lesson 4.2: Sleep Journal Analysis: Are you getting enough quality sleep? Rationale: This lesson focuses on students applying what they learned in the previous lesson to analyze their sleep journals. The students were previously given a sleep journal to record how much sleep they got each night for a week, along with the amount of caffeine they drank, and their school performance. Using their journals, the students will calculate their own sleep patterns and sleep debts, and determine whether there are correlations between their sleeping behavior and the amount of caffeine they consume and whether either or both impact outcomes like their school grades. Activities: This lesson focuses on analyzing the students’ sleep journals. The analysis can be done as a whole class activity or the students can be divided into groups depending on how facile they are individually at calculations and plotting graphs. The students will use their sleep journal and the data derived from the class to calculate specific pieces of information about their sleep patterns, behaviors and impacts. You will then ask them to determine correlations between the sleep patterns and other behaviors as well as potential impacts. They will be asked to draw conclusions about the potential impact of sleep patterns on outcomes. Homework: Students will be asked to write a short report summarizing the findings of the sleep journal analysis and offer potential solutions to any problems the data has identified. Lesson Plan Do Now: Using their sleep journals, students will be asked to calculate a list of averages. Discussion (5 minutes): The PowerPoint is used to discuss how NREM and REM sleep occur in stages throughout the night. Activity (30 minutes): Analysis of sleep journals. After compiling class data, students will break off to calculate data from their sleep journals. Wrap-up (10 minutes): Students will summarize what they have found and the correlations they can make from the data. Homework: Students will write a report summarizing the findings of the sleep journal analysis and offer potential solutions to any problems the data has identified Do now (5 min): Give each student a copy of Neuro Unit 4.2 Sleep Journal Analysis Worksheet which can be found in the materials folder of this lesson. Instruct the students to complete Part 1 which asks them to calculate their average time spent sleeping, caffeine intake and grades for the duration of their sleep journal. The students are also asked to find the average of these values for their table group. Activity and Discussion (30 min): Gather class information calculate the class averages of: and Use this PowerPoint slide to collect class wide data for the sleep journal analysis. Have the students share their table averages of hours slept, caffeine intake and grades for the week. The students should report their table data and you will fill in the chart on the PowerPoint slide. Have the class calculate the class averages as well as make note of the lowest and the highest values in each category to give an idea of the range. Mark these values on the PowerPoint slide and have students record these values in the chart in Part 1 on their Neuro Unit 4.2 Sleep Journal Analysis Worksheet. Once all the students have the class values filled in Part 1 of the worksheet, have students work in small groups to complete Parts 2 & 3 of the worksheet. Give the students 15 minutes to complete this task. Part 2 asks students to plot a graph to illustrate the data. The graph might look something like the graph to the right that shows that caffeine intake goes down and sleep goes up at the weekends. Part 3 ask the students to analyze the data collected and graphed. The class will discuss this analysis later. NREM and REM sleep occur in stages. Tell the students that another important component to analyzing sleep is analyzing how much time is spent in each of the sleep stages. Use this slide to remind students of the five different stages of sleep and how they occur sequentially during the night. The stages occur in cycles throughout the night Use this slide to demonstrate that the stages of sleep occur in cycles throughout the night. Remind students what each sleep stage is by describing what is happening at each stage. Stage 1 & 2 – You first fall asleep but are not yet in a deep sleep. Stages 3 & 4 – You are in a deep, restful sleep. Your breathing and heart rate slow down, your body is still. Stage 5 – Your brain is active and you dream. Your eyes move under your eyelids in REM sleep. Talk the students through the chart. Explain that as we enter sleep we gradually progress from stage I to stage II to stage III to stage IV, then back to stage III, to stage II and then to REM. After REM we progress to stage II then to stage III, etc. Be sure to point out where deep sleep (colored red) and when REM sleep (colored blue) occur. Ask the students – what happens to the periods of stage 4 or deep sleep as the night progresses? They get shorter. Ask the students – what happens to the periods of REM sleep as the night progresses? They get longer. Have students work in small groups to complete Part 4 of their worksheets which asks them to calculate how many sleep cycles and how much REM/NREM sleep they got during the school week and on the weekend. It also asks them to compare their results with the idealized young adult in the graph. If the students are going to bed late and getting up early they will be getting enough deep sleep but not enough REM sleep and sleep cycles. At the weekend they will probably be sleeping more and will fulfill their sleep debts. The question is whether they are fulfilling their sleep debt adequately. Give the students 10 minutes to complete this task. Wrap Up: Are you getting enough sleep? Have students review the data they have gathered to make sure everyone has a complete set for homework. Ask the students – what happens if you don’t get enough sleep? The students read about sleep deprivation for homework last night. So they should be familiar with the many effects of not getting enough sleep including: fatigue, daytime sleepiness, clumsiness and weight loss or gain, decreased concentration, decreased memory, decreased performance. Ask students who represent the low and high points of each category to talk about how their data fits with the other measurements – Does the person who gets the most sleep drink the least caffeine and vice versa. Does the person who has the highest grades drink the least caffeine and sleep the most, or is there no obvious correlation. Homework: For homework, have the students complete Part 5 of their worksheets which asks them to write a report about how sleep patterns correlate to behavior. The students should write one paragraph to answer each of the following questions: • Are you and the class getting enough total sleep and quality sleep time? • How does your sleep behavior on the weekends relate to your behavior during the week? • What are the correlations between sleep patterns and other behaviors – drinking caffeinated beverages and school performance? If there is no obvious correlation between sleep patterns and other behaviors (consuming caffeine and school performance), have the students examine REM vs NREM sleep. Students are probably getting adequate NREM sleep, this would suggest that performance is driven by NREM sleep. On the contrary, a correlation would suggest that REM sleep is important in performance even if no ill effects are suffered if people are deprived of it. This would be a new finding. Lesson 4.3: What makes us go to sleep and wake up? Rationale: This lesson is intended to demonstrate a simple neuronal circuit that regulates the sleep-wake cycle. Students will learn how neurons located in different parts of the brain perform different functions in regulating sleep and wakefulness. They will learn that a switch sensitive to outside stimuli is used to control the sleep-wake cycle and they will learn what can happen when the control of sleep and wakefulness goes wrong. They will be introduced to the idea of using an animal model to mimic the disruption in the sleep-wake cycle. Students will also be introduced to a key concept in neuronal circuit function – that circuits rely on both inhibition and excitation to function. Discussion: Students will begin the lesson by trying to determine what makes us fall asleep and what makes us wake up. To challenge their answers to these questions, they will be shown a video of Skeeter, a narcoleptic poodle. Students will then work through a PowerPoint with the teacher that describes the sleep-wake circuit. The PowerPoint is interactive and students will be required to make deductions and answer questions about how the circuit works. Activity: After learning about the sleep-wake circuit, students will be asked to predict what causes Skeeter’s narcolepsy. The lesson concludes with a video about research being done with dogs on narcolepsy. Homework: Students will complete a worksheet about the research being done on the role of orexin in the sleep-wake circuit. Lesson Plan Do Now (5 min): The students answer questions about what makes us fall asleep and what makes us wake up to introduce the concept of the stimuli required to keep us awake and allow us to sleep. Discussion (30 minutes): Using the PowerPoint, the class will piece together the flip-flop switch which underlies the sleep-wake circuit. The discussion will focus on: o The involvement of external stimuli in regulating the sleep-wake cycle o The two components of the sleep-wake circuit (arousal neurons and VLPO) and emphasize that when they are active they inhibit each other Wrap-up (10 minutes): You show the students a video about research done on narcoleptic dogs as an illustration of defects in the sleep/wake circuit. Homework: Students will complete a worksheet about the research being done on the role of orexin in the sleepwake circuit. Do now: Have the students work with a partner to answer the questions on the slide. Give the students 5 minutes to complete this task. Discussion: So, what makes this happen? Show the students the video of Skeeter, a narcoleptic poodle. This video is embedded in the PowerPoint. Ask the students – Do any of your answers to the previous explain Skeeter’s behavior. Most likely none of their answers will explain narcolepsy, but this video is used as a jumping point to show the students what we have learned about the sleep wake circuit. Specific brain areas keep us awake and other areas put us to sleep. This slide introduces the idea that specific areas of the brain need to interact with each other in order to regulate the behavior. This concept of multiple parts of the brain working together is the idea of the circuit. Tell the students that specific regions in our brain keep us awake and others cause us to fall asleep. Tell the students that the ‘wake up’ area is made of arousal neurons found in the brainstem. Ask the students – How could these neurons control wakefulness? The arousal neurons function because they connect directly with the cortex. One of feature of these neurons is that they make synapses all the way along their path to the cortex so they can influence many areas. Tell the students that the “go to sleep” area is located in the hypothalamus and that the hypothalamus is critical in maintaining body homeostasis. Ask the students – What is homeostasis? Homeostasis is the balance that is required to maintain physiological function. Tell the students that neurons in the ventrolateral preoptic nucleus (VLPO) of the hypothalamus help to regulate sleep. Specific brain areas keep us awake and other areas put us to sleep. The slide abstracts the two brain areas and shows them as a schematic. Tell the students that you can represent the two brain areas pictured on the previous slide with this schematic. We will use the schematic to describe how the brain areas work. Reiterate that connections between the two areas are bidirectional. When the “go to sleep” area is active, we fall asleep and when the “wake up area” is active, we are awake. The “go to sleep” area is actually called the VLPO, and the “wake up area” is actually called arousal neurons. These terms are used interchangeable, so get the students used to both names now. Ask the students – But how do these areas know what the other is doing? (This is the classic -Does the right hand know what the left hand is doing?) Based on their previous studies on pain, the students should be able to immediately say that there would be axonal connections between the two areas. Make sure they understand that the connections have to go in two directions. Students are likely to think that communication between the two areas requires them to activate each other. This is not necessarily the case as the next few slides will demonstrate. The two areas connect with each other. Can you predict how they connect? Ask the students – How would these two areas connect? The students might be able to figure out that since the two areas have opposing actions, they should inhibit each other. However, if the students need help getting to the answer, ask them what type of synapse would the “wake up” area need to make with the “go to sleep” area in order to not let it put yourself to sleep? The two areas connect with each other. They inhibit each other. This slide introduces inhibitory synapses into the schematic. The students have discussed inhibitory synapses in previous lessons about synaptic transmission, but it is important to refresh their memory since inhibitory synapses are an important concept in neuroscience. Explain to the students that as the circuit is drawn now, when each area is active it will inhibit the activity of the other area. Ask the students whether it could work as drawn? No because each component inhibits the output of the other. We would either constantly be asleep or constantly be awake, there is no balance between the two. Ask the students whether they can come up with an alternative circuit. To wake up, the ‘wake up’ area needs to be more active than the ‘go to sleep’ area. Ask the students - what would happen if the ‘wake up’ area was more active than the ‘go to sleep’ area? We would wake up because the ‘wake up’ area will inhibit the activity of the ‘go to sleep’ area. To sleep the ‘go to sleep’ area needs to be more active than the ‘wake-up’ area. Ask the students – what needs to happen for us to be able to go to sleep? For us to be able to go to sleep, the ‘go to sleep’ area needs to be more active than the ‘wake up’ area so that it can inhibit the ‘wake up’ area and also output sleeping behaviors. But how is the transition from sleep to wake (and vice versa) controlled? Ask the students – What makes us feel tired and sleepy? The students will likely have a variety of answers. Typical answers could include: o They feel tired when it’s dark, which could apply to rainy or grey days, as well as to nighttime. o They feel tired when they haven’t slept in a while – this gets into the circadian clock. o They feel tired after a big meal or when they are really relaxed. Animate the slide to show the students three possible answers. Ask the students - What makes us feel awake and alert? The students will likely have a variety of answers. Typical answers could include: o They feel awake when it’s light. o They feel awake and alert when they just slept or when they feel stressed. Animate the slide to show the students three possible answers. Remind the students that we needed an external stimulus to drive the circuit. The light/dark cycle acts as that stimulus. Tell the students that neurons that are sensitive to these signals, particularly light and dark, switch the “wake up” and “go to sleep” areas on and off. The Orexin neurons in our hypothalamus are activated by signals that keep us awake. Use this slide to describe the biology of the orexin neurons. Tell the students that orexin neurons in the hypothalamus actually drive the sleep/wake cycle. These neurons are called orexin neurons because they use a chemical neurotransmitter called orexin. Tell the students that the orexin neurons are stimulated by light as well as the other signals that keep us awake. Orexin neurons are activated by signals that keep us awake, and then activate the arousal neurons. Use this slide to show the students how the orexin neurons fit into the circuit. Walk the students through this schematic drawing. They have seen a similar drawing earlier in this lesson, and the only addition is that the orexin neurons are now stimulating the arousal neurons. Ask the students – What is the effect of the orexin neurons activating the arousal neurons? The students should be able to answer that the arousal neurons can then inhibit the VLPO neurons, and we wake up. Orexin neurons are activated by signals that keep us awake, and can activate the arousal neurons. Ask the students – Other than light, what keeps us awake? The students will probably answer things like stress and/or caffeine. Animate the slide to show the students that orexin neurons are sensitive to signals other than light which then keeps us awake. Tell the students that orexin neurons are not only responsive to light they can also respond to energy balance and emotional states – that is why you can’t sleep sometimes when you’re tense or stressed, or why you wake up too early. What happens when the orexin neurons are switched off? Use this slide to show the students how the circuit switches to sleep. When orexin neurons are not stimulated (its dark, your blood fat levels are high, you feel calm) they do not activate the arousal center. Now the arousal center cannot activate the sleep center, so sleep occurs. Ask the students – what would be the effect of turning off the orexin neurons? The students should be able to predict that you would fall asleep because the “go to sleep” neurons are no longer inhibited, and so they then can inhibit the “wake up” area. Use the next slide to answer this question for the students. What happens when the orexin neurons are switched off? Use this slide to show the students how the circuit switches to sleep. Tell the students that when the orexin neurons are switched off, arousal neurons are switched off too and we fall asleep. Activity: Think, Pair, Share. Use this slide to remind the students of how we started this discussion – Skeeter and his inability to stay awake. Ask the students – Given what you just learned about the sleep-wake circuit, can you predict what causes Skeeter’s narcolepsy? After 5 minutes, have some of the student groups present their ideas of what causes Skeeter’s narcolepsy. Wrap Up: Narcolepsy Tell the students that researchers have used dogs as a model of narcolepsy. Show them the video to demonstrate what researchers have learned about orexin’s role in the sleep-wake circuit. The video has been embedded into the PowerPoint. Homework: Homework: What causes narcolepsy? Tell students that in 1999 researchers identified the gene responsible for causing narcolepsy in dogs. The gene identified was a mutation in the receptor for orexin. The mutation caused the receptor to be defective. Make sure the students know that this means dogs with this gene would not be able to detect orexin. Tell the students that for homework they will apply what they have learned about the flipflop switch to figure out what causes narcolepsy. For homework have the students complete Neuro Unit 4.3: Homework which can be found in the materials folder of this lesson entitled: Neuro Unit 4.3 Homework. This homework is designed to walk students through the research done on the role of orexin in the sleep-wake circuit. Lesson 4.4: Regulating output: How circuits use excitation and inhibition for control Rationale: This lesson is intended to demonstrate how different arrangements of excitatory and inhibitory connections can regulate output from a neuron both spatially and temporally. The concept of inhibitory control sets the stage for later lessons in this unit that examine the clinical consequences when inhibition is abnormal, and for later units in which students will examine more complex circuits. Activity: The students begin this lesson by reading a short description of the circadian clock in the SCN. After reading about the circadian clock students work with a partner to figure out how it would interact with the sleep-wake circuit (flip-flop switch) discussed in the previous lesson. After a short discussion, students will divide into groups of 6 to solve an engineering problem about how to regulate synaptic output. Homework: For homework students will complete a worksheet that is designed to get them thinking about the importance of controlling excitation to a specific area. Lesson Plan Do Now (15 min): Students complete Neuro Unit 4.4 Do Now Worksheet which includes a brief description of the circadian clock in the SCN and then asks them to figure out how this biological clock interacts with the sleep-wake circuit discussed in the previous lesson. Activity (20 minutes): Students will divide into groups of 6 to solve an engineering problem about how to regulate synaptic output. Wrap-up (10 minutes): Students share their solutions with the class. Homework: The students will complete a worksheet on inhibitory control of excitatory circuits. Students will complete a worksheet about the research being done on the role of orexin in the sleepwake circuit. Do now: Have the students work with a partner to complete Neuro Unit 4.4 Do Now Worksheet which is included in the materials folder for this lesson. This worksheet includes a brief description of the circadian clock in the SCN and asks the students to figure out how this biological clock interacts with the sleep-wake circuit discussed in the previous lesson. Discussion: Where does the SCN connect? And how? Ask the students – How does the SCN connect to the sleep-wake circuit? Allow a couple of groups of students to present their answers to the class. The answer is on Slide 3. The SCN and the sleep-wake circuit in light Use this slide to help the students to understand how the circadian clock functions with the sleepwake circuit. Ask the students – what is the effect of light on the orexin neurons? Light stimulates the orexin neurons to then stimulate the arousal neurons which then inhibit VLPO. Ask the students – what is the effect of light on the SCN? Light causes the SCN to inhibit the PON which then does not produce melatonin. The SCN and the sleep-wake circuit in darkness Ask the students – what happens to the orexin neurons in darkness? They turn off, which then turns off the arousal neurons. Ask the students – what happens to the SCN in darkness? It turns on and stimulates the PON which induces the release of melatonin. Ask the students – We know that the SCN makes a connection with the VLPO. What type of connection must this be? Excitatory or inhibitory? Excitatory Animate the slide to show the students that the SCN makes an excitatory connection with the VLPO. Ask the students – We know that the SCN makes a connection with the orexin neurons. What type of connection must this be? Excitatory or inhibitor? Inhibitory Animate the slide to show the students that the SCN makes an inhibitory connection with the orexin neurons. Emphasize the following points The SCN acts oppositely to the orexin neurons. When orexin is off, the SCN is on. The combination of excitation and inhibition is critical to control a circuit. Activity: Building Neural Circuits Prepare the students for the activity. Tell them that they will be working in groups to engineer a neural circuit using excitatory and inhibitory synapses. Divide the students into groups. Give each group a copy of Neuro Unit 4.4 Engineering Worksheet found in the materials folder for this lesson. This activity has students work in groups to assemble a neuronal circuit to meet the requirements specified with the different components listed on the engineering worksheet. As the students are assembling their circuits make sure they understand that each neuron can only work when it has been stimulate. Give the students 15 minutes to assemble their circuits and then have one or two student groups present their solutions to the class. A Possible Neural Circuit This slide presents one possible solution to the activity. Ask the students what each type of inhibition is called? The answers are on the next slide. A Possible Neural Circuit This slide demonstrates the two different types of inhibition. The one on the right is called feedback inhibition because the same output that excites ends up inhibiting itself. The one on the left is called feed forward inhibition because it comes from a different unique source. Why do we need feedback control? This slide shows a simplified version of the previous circuit. Review the excitatory and inhibitory inputs and how the circuit works. Tell the students that we are now going to look at the synaptic level. Ask the students whether they remember what effects excitation and inhibition has on the postsynaptic membrane? This maybe a stretch of memory! Excitation causes the membrane to depolarize, inhibition causes it to hyperpolarize. How depolarization leads to hyperpolarization This slide reviews the effects of an excitatory input on an inhibitory neuron. The excitatory neuron causes depolarization (and thus activation) of the inhibitory neuron. Once the inhibitory neuron is depolarized (active) it fires an action potential. When the inhibitory neuron fires an action potential, it causes its postsynaptic cell to hyperpolarize. The notion that two things happen to the inhibitory neuron – it gets excited and then inhibits the post synaptic cell are important in order to understand the pathway. Ask the students whether hyperpolarizing the postsynaptic membrane will make the membrane more or less sensitive to a new stimulus? Less sensitive. Hyperpolarization shifts the membrane potential away from its resting potential, so it takes longer to respond to another signal. Feedback inhibition The next set of slides put depolarization/hyperpolarization into the context of the feedback inhibition. Point out to the students that one of the synaptic connections is excitatory and one is inhibitory. Also emphasize that the inhibitory connection is made on the same neuron that excites the inhibitory neuron. Feedback inhibition Tell the students that the cell body fires an action potential. Ask the students – What will be the effect on the inhibitory neuron? The inhibitory neuron will depolarize. Feedback inhibition Show the students that the inhibitory neuron depolarizes and fires and action potential. Ask the students – What will be the effect on the cell body? The cell body will hyperpolarize. Feedback inhibition Show the students that the cell body hyperpolarizes. This happens because the inhibitory neuron releases a neurotransmitter that causes the postsynaptic cell (in this case our initial neuron) to hyperpolarize, essentially switching this pathway off for a while. Why do we need feedback control? Ask the students – So, we have learned that feedback control can switch off a pathway for a while. Why is this important? Wouldn’t it be just as easy to do it with feed forward inhibition? Feedback inhibition allows for very tight regulation of activity. Ask the students what simplifications we have made within our circuit diagram? Does this really represent neural circuits in our brains? The most important simplification is in what the output neuron looks like. We have all the inputs coming into one dendrite and all the outputs going down one axon. This type of design is only true for a very few neurons in the nervous system. Neurons in which feedback control is important Tell the students that neurons in the nervous system do not have only one input and output. Tell the students that 99% of our neurons look like this – they may have thousands of dendrites and hundreds of thousands of synapses and highly branched axons. Feedback inhibition is important in this neuron to allow different inputs a chance to excite the output cell (remember the inhibition is on the inputting dendrite, not on the output area). Neurons in which feedback control is important Tell the students that another type of neuron for which feedback inhibition is particularly important are those that don’t have a single long axon (like your motor neurons). Feedback inhibition is important in these neurons because it keeps activity confined to a specific area of the brain. Homework: Have the students complete the Neuro Unit 4.4 Homework Worksheet which is included in the materials folder of this lesson. This homework assignment is designed to get students thinking about control excitation which leads into the next lesson’s discussion of epilepsy. Lesson 4.5: Epilepsy Rationale: This lesson focuses on epilepsy. Because epilepsy is caused by abnormal disordered neuronal activity, this lesson provides the medical application of abnormal neural circuits. The lesson begins with an activity to demonstrate the consequence of removing inhibition within a circuit. After a discussion of epilepsy, including the symptoms, types and origin of seizures, the students will analyze three patients’ EEGs and give them a diagnosis. The lesson concludes with an overview of the current treatments for epilepsy. Activity: This lesson includes two activities. The first activity, included as the “Do Now”, is an extension of the discussion from the previous lesson about the importance of inhibition within neuronal circuits. The students will analyze a circuit and determine the consequences of removing the inhibition from within the circuit locally and at a distance. The second and main activity of this lesson has students analyzing EEGs from three patients who suffer from seizures. The students will examine the EEGs and answer questions to help diagnose the type of seizures the patients are having. Homework: Students will read a short article entitled “Controlling Epilepsy” by Christian Hoppe from Scientific American Mind. This article presents the story of one woman’s journey to get her epilepsy properly diagnosed and treated. Lesson Plan Do Now: Examination of circuit and predict effect of removing inhibitory neurons. Discussion: The teacher uses the PowerPoint to have a Socratic discussion of epilepsy, including partial and generalized seizures as well as their symptoms and causes. Additionally, the teacher reviews the EEG and introduces how they are used to diagnose epilepsy and determine the origin of a seizure, called the seizure focus. Activity: Exam EEGs of partial and generalized seizures. Based on location of seizure activity students will determine if the patient is having a partial or generalized seizure as well as predict behavioral symptoms displayed. Wrap up: Treatments of epilepsy will be presented, including drugs, surgery, and vagus nerve stimulation. This discussion introduces important medical issues that are further discussed in the homework assignment. Homework: Read Scientific American Mind article “Controlling Epilepsy” and answer questions Students will complete a worksheet about the research being done on the role of orexin in the sleepwake circuit. Do Now: Have the students work with a partner to complete Neuro Unit 4.5 Do Now Worksheet contained in the materials folder for this lesson, entitled: Neuro Unit 4.5 Do Now Worksheet. Alternatively, have the students work on the problem presented on this slide as it is the first part of the worksheet and will get the students thinking about the necessity for balance between excitatory and inhibitory outputs. Discussion: Removing Inhibition: The Effect Locally Use this slide to work through the Do Now with the students. Ask the students – what effect would removing the two blue inhibitory neurons have on this circuit’s activity? Since the two red neurons are excitatory and make synapses on each other, without the inhibition provided by the two blue neurons the circuit’s activity would greatly increase. Animate the slide to show the students that the local circuit’s activity would greatly increase when the inhibition is removed, represented by a red upward facing arrow. Removing Inhibition: The Effect Distantly Ask the students – what effect would removing the two blue inhibitory neurons within the local circuit have on the activity of these distant excitatory neurons? Again, by removing the inhibition provided by the two blue neurons, you are increasing the activity of the local red excitatory neurons. Because the local excitatory neurons make synapses with the distant neurons, this increase in activity will propagate to the distant excitatory neurons. Since these distant neurons are also excitatory, they will continue to propagate this increase in excitatory signal. Animate the slide to show the students that the distant circuit’s activity will also increase when inhibition is removed from the local circuit. Can anyone think of a condition caused by abnormal disordered neuronal activity? Ask the students – Can anyone think of a condition caused by abnormal disordered neuronal activity? The students may come up with a variety of answers. Since many neurological disorders cause abnormal neuronal activity, there are a number of reasonable answers to this question, including stroke, Parkinson’s disease, and Alzheimer’s Disease. However, we want to focus on epilepsy, the only disorder that we currently know is caused by abnormal neuronal activity. Epilepsy Use this slide to introduce epilepsy. Tell the students that epilepsy is a chronic neurological condition that results in unprovoked seizures. Ask the students – What is a seizure? Students will likely answer that a seizure is when someone convulses or shakes uncontrollably. While this response is not incorrect, it also is not complete. If students answer with this, foreshadow the fact that there are different types of seizures and not all result in convulsions of the entire body. Tell (and animate the slide to show) the students that seizures are the changes in behavior caused by disordered abnormal electrical activity in the brain. Symptoms of Seizure Use this slide to discuss the symptoms of seizures. Tell the students that there are many different symptoms to seizure, and that the symptoms are characterized into two groups: Positive and Negative. Positive symptoms are any symptoms that involve the addition of an abnormal behavior, for example jerking one’s arm. Negative symptoms are any symptoms that involve the loss of a normal behavior, for example temporary losing one’s sight. Symptoms of Seizure Ask the students – what do you think determines what type of symptoms patients experience? Given the picture on this slide, hopefully students will be able to figure out that the symptoms patients experience directly relates to the brain areas affected by the seizure. If students need help answering this question, ask them, what is the function of the occipital lobe? Vision. If a seizure disrupted the neural circuits and thus the function of the occipital lobe, what might the patient have problems doing? Seeing. Remind the students that each part of our brain has a very specialized function and when a seizure disrupts that function, patients experience different symptoms. Use this figure to show the students that when seizures are localized to specific areas of our brain, the function of the specific area is disrupted. For example - when patients experience a seizure in their temporal lobe (responsible for audition), patients can have either auditory hallucinations or problems hearing. Types of Seizure Use this slide to introduce the two types of seizure: Partial and Generalized. Tell the students that partial seizures occur when abnormal electrical activity remains in a limited area of the brain, and generalized seizures occur when abnormal electrical activity extends throughout the entire brain. Partial Seizure Use this slide to explain how a partial seizure develops. Tell the students that partial seizures originate within a small group of neurons called a seizure focus, and that partial seizures start due to a loss of inhibitory control. Ask the students – does this remind you of anything? Yes! The do now! Partial Seizure: Spread from Seizure Focus Ask the students – In the Do Now activity, what happened when the increased excitatory activity from the local circuit spread to a distant circuit? The activity also spread. Show the students that while a partial seizure starts in one specific area, the seizure focus, it can spread to other areas of the brain. Ask the students – What is the function of the thalamus? The thalamus filters incoming stimuli sends/redirects the information to the necessary parts of the brain. You can think of the thalamus as the post office of the brain – receiving letters and packages (stimuli) and then delivering to addresses (different parts of the brain). Ask the students – What do you think would happen if a partial seizure spread to the thalamus? Since the thalamus redirects and sends information all over the brain, if a partial seizure spread to the thalamus, it would then be redirected over the entire brain. Partial Seizure: Spread from Seizure Focus Use this slide to demonstrate the last point made on the previous slide. Tell the students that when a partial seizure spreads to the thalamus, the thalamus then spreads it throughout the entire brain. Emphasize the point that while a partial seizure starts in a specific brain area of the brain; it can spread throughout the entire brain. When a partial seizure spreads throughout the entire brain, its symptoms are very similar to a generalized seizure. However the difference is that generalized seizures start within the thalamus and spread simultaneously to both sides of the brain. This last point will be more obvious on the next slide. Generalize Seizures Use this slide to explain how a generalized seizure develops. Tell the students that a generalized seizure originates within the thalamus. Also, because generalized seizures originate in the thalamus, seizure activity starts simultaneously in both sides of the brain. Measuring Seizures Ask the students – What instrument or recording device could we use to measure a seizure, keeping in mind that a seizure is abnormal electrical activity of the brain? Hopefully the students remember that an EEG measures the electrical activity of the brain, and are able to use that fact to answer this question. Animate the slide to show the students that EEGs are used to measure seizures. Tell the students that EEGs measure the electrical activity of the brain, and doctors use them to help diagnose seizure. Measuring Seizures Use this slide to remind the students of the placement of electrodes for the EEG. This will be important in diagnosing where seizures are occurring within the brain. Remind the students that the placement of electrodes on the head allows doctors to determine where within the brain electrical activity might be abnormal. The placement of electrodes are standardized for all EEGs and the coding system used is displayed on this slide. The students saw this coding system before, but quickly review it to refresh their memories. Measuring Seizures Tell the students that this is a normal EEG. Draw their attention to how the electrode numbers are written to the left hand side. Ask the students – if the recording from one or two electrodes was abnormal, what would that say about that part of the brain? That the part of the brain the electrode records from is abnormal and perhaps it is the seizure focus. Measuring Seizures Use this slide to show the students what a seizure looks like on an EEG. Show the students that the EEG for the partial seizure only has abnormal high activity for some but not all of the electrodes. Also, show the students that once abnormal activity begins in the one area, it slightly disrupts activity in other areas as well – note the bottom electrode leads. Show the students that the EEG for the generalized seizure has abnormal high activity for all the electrodes and that this abnormal activity beings at the same time for all the electrodes. Ask the students – How would a doctor know via EEG if a patient has had a partial seizure that has spread throughout the entire brain or if a patient has had a generalized seizure? The EEG for a partial seizure with spread will show abnormal activity beginning at specific electrodes which then spreads to all leads. The EEG for a generalized seizure will show abnormal activity beginning at the same time in all electrodes. Activity: Analyzing EEGs Prepare the students from the activity. Tell the students that they will be working in pairs to analyze EEGs and help diagnose patients. Give each student a copy of Neuro Unit 4.5 Activity Worksheet which is included in the materials folder for this lesson, entitled: Neuro Unit 4.5 Activity Worksheet. Patient 1 Ask the students, is this patient having a partial or generalized seizure? Partial seizure What electrodes show increased activity? T3-T5 T5-O1 What brain regions do these electrodes record from? T – Temporal Lobe Right Side because odd numbered electrodes What behaviors does this area control? What symptoms would a patient experience? Auditory, the patient might have auditory hallucinations or loss of hearing. Patient 2 Ask the students, is this patient having a partial or generalized seizure? Partial seizure What electrodes show increased activity? F8-T8 T8-P8 To a lesser extent – FP2-F8, and P8-O2 What brain regions do these electrodes record from? T – Temporal Lobe P – Parietal Lobe Left side because even numbered electrodes What behaviors does this area control? What symptoms would a patient experience? Temporal - Auditory, the patient might have auditory hallucinations or loss of hearing. Parietal – Movement, the patient might have motor abnormalities Ask the students – is this seizure spreading at all throughout the brain? Yes. You can see that other electrodes start to show abnormal activity as the seizure progresses. Patient 3 Ask the students, is this patient having a partial or generalized seizure? Generalized seizure What differences do you see in this EEG from the previous EEGs? This EEG has all electrodes showing seizure activity at one time. Wrap Up: Treatment Use this slide to introduce the different treatment options for epilepsy. Tell the students that often patients are treated with medicine, but sometimes surgery is needed to remove the brain tissue that is causing the seizure. Additionally, a new method which is a sort of like a brain pace maker has also been developed. It works by giving regular pulses to the vagus nerve which keeps the brain from seizing. Tell the students that for homework they will read more about different treatment options. Homework: Have the students read “Controlling Epilepsy” by Christian Hoppe 2006, from Scientific American Mind. It tells one woman’s story to treat her epilepsy. This can be found in the materials folder of this lesson.