I. Course Title Neurobiology II. Course Description In this course, students will be exposed to many of the exciting new discoveries related to the brain and how it functions. The course is not intended to be an introduction to neurobiology (which is more appropriately addressed at the college level). Rather, it is intended to give students an opportunity to learn about such topics ranging from how memories are formed and stored to the mechanism of depression; from gender differences in brain structure and function to synesthesia (a condition whereby peoples senses get mixed up); from the causes of and treatments for Alzheimer s disease to the effects of cocaine on the brain. The class modus operandi is similar to a graduate school seminar: students will lead and participate in discussions on specific topics, based on readings from the scientific literature. There is a heavy emphasis on the interpretation of data, analysis of methodology, and experimental design. Furthermore, creative thought is required for the discussions on the best path to take for future research. Specifically, Neurobiology is a post-ap biology course and approximately 60% of the time is dedicated to the discussion of recently published neuroscientific literature. Discussions focus on primary research articles, with secondary and review articles integrated as supporting documents. Students learn neurobiological concepts from the literature; however, emphasis is on the development of skills needed for reading and understanding primary research reports, analysis of experimental design and of the conclusions drawn by researchers, as well as developing skills for communicating complex material to non-scientific audiences. The remaining 40% of the course is divided roughly evenly between introductions to two things. First, students are introduced to fundamental neuroscience (concepts and technologies). This occurs prior to any article discussions. Second, students are introduced to some basic tools and practices for conducting neuroscience research. The culminating project in Neurobiology is a proposal for neuroscience research, complete with justification, experimental design specifications and explanations of the methodology proposed and intended statistical analysis of data. III. Performance Indicators Standard 1 (modified from State of VA Biology Std 1; note that standard s 1.j and 1.k are not included) The student will demonstrate an understanding of scientific reasoning, logic, and the nature of science by actively analyzing published primary reports of investigations. Benchmark 1.a Observations of living organisms, including humans, are recorded in the lab and in the field. Indicator 1.a.1 Students will identify the use of living organisms, including humans, in the discussed experiments, some of which will be observational studies. Benchmark 1.b (addition to State of VA Biology Std 1, TJHSST-specific) Non-human living organisms and systems are utilized as models to study human conditions. Indicator 1.b.1 Students will identify and explain the purpose of non-human organisms and systems in experiments designed to study human conditions. Indicator 1.b.2 1
Students will describe the advantages and disadvantages of using model organisms and systems in experiments designed to study human conditions. Benchmark 1.c Hypotheses are formulated based on direct observations and information from scientific literature. Indicator 1.c.1 Students will explain whether or not, and in what way hypotheses have been based on both preliminary observations and scientific literature. Indicator 1.c.2 Students will identify and describe scientific ideas that may be changed or modified due to the published research report at hand. Benchmark 1.d Variables are defined and investigations are designed to test hypotheses. Indicator 1.d.1 Students will explain whether or not hypotheses appear to be based on cause-and-effect relationships and are testable. Indicator 1.d.2 Students will identify the control, independent and dependent variables used in the experiment and assess the effect of the number of trials utilized. Benchmark 1.e Graphing and arithmetic calculations are used as tools in data analysis. Indicator 1.e.1 Students will identify when computational tools are used for analysis of experimental data. Indicator 1.e.1 Students will distinguish between qualitative and quantitative data and analyze the reliability of the methods, technologies or paradigms used in data analysis. Benchmark 1.f Conclusions are formed based on recorded quantitative and qualitative data. Indicator 1.f.1 Students will distinguish between qualitative and quantitative data and analyze the reliability of the methods, technologies or paradigms used to collect the data. Indicator 1.f.2 Students will use evidence, apply logic, and construct an argument for or against authors conclusions based on reported data. Indicator 1.f.3 Students will explain the application and purpose of the particular method used for statistical analysis and whether the statistical conclusions appear to reflect the trend(s) found within the data. Benchmark 1.g Sources of error inherent in experimental design are identified and discussed. Indicator 1.g.1 2
Students will use evidence, apply logic, and construct an argument for or against authors experimental design (hypothesis, methods, etc.) Benchmark 1.h (addition to State of VA Biology Std 1, TJHSST-specific) Sources of bias in experimental design are identified and discussed. Indicator 1.h.1 Students will discuss the validity or limitations of control conditions utilized. Indicator 1.h.2 Students will use evidence, apply logic, and construct an argument for or against authors experimental design (hypothesis, methods, etc.) Indicator 1.h.3 Students will recognize that in order to ensure the validity of scientific investigations, they must be evaluated by other members of the scientific community. Benchmark 1.i Validity of data is considered. Indicator 1.i.1 Students will discuss the validity of results; consider levels of data accuracy and precision, levels of statistical confidence, and/or sources of experimental error (e.g. discuss the number of trials or degree of variance in the data and how these factors could be improved). Indicator 1.i.2 Students will recognize and discuss contradictory or unusual data. Benchmark 1.j Chemicals and equipment are used in a safe manner. Indicator 1.j.1 Students will recognize and discuss the importance and limitations of the use of pharmaceuticals in human subjects research. Indicator 1.j.2 Students will recognize and discuss any special measures meant to protect the health and safety of the researchers during experimentation which are explicitly stated in the assigned scientific reports. Benchmark 1.k (modified from State of VA Biology Std 1.i, TJHSST-specific) Appropriate technology such as computers, imaging technologies (e.g. FMRI), and that which is used in molecular/cellular biology research (e.g. optogenetics, cell culture) is used for gathering and analyzing data. Indicator 1.k.1 Students will explain the choice of technology for data collection, as well as the authors interpretation of its outputted data. Indicator 1.k.2 Students will discuss the pros and cons of, and the strengths and weaknesses of the choice and use of technology in the collection and analysis of data. Benchmark 1.l (modified from State of VA Biology Std 1.i, TJHSST-specific) 3
Appropriate technology such as computers, and graphing and statistical software is used for communicating results, modeling concepts, and simulating experimental conditions. Indicator 1.l.1 Students will discuss the use of technology for simulation, the simulation model itself and particularly the robustness and relevance of the model for studying human conditions. Indicator 1.l.2 Regarding data tables, graphs and/or figures in articles, students will discuss the pros and cons of, and the strengths and weaknesses of chosen the format for data presentation. Benchmark 1.m Alternative scientific explanations and models are recognized and analyzed. Indicator 1.m.1 Students will determine which data support/do not support the stated hypothesis, and propose new hypotheses and directions for continued research. Indicator 1.m.2 Students will compare and contrast competing hypotheses, results or conclusions, for example, found in the other literature covered during the course. Benchmark 1.n Current applications of biological concepts are used. Indicator 1.n.1 In discussions of current research, students will apply their conceptual understandings from Advanced Placement Biology including and not limited to cell signaling events and pathways, regulation of homeostasis, neuronal signaling events, the basis and effect of genetic anomalies, behavior as a phenotype which scientists measure, etc. Indicator 1.n.2 Students will identify, analyze and discuss the unfamiliar biology concepts which are applied and evident in the published research reports. Standard 2 (TJHSST-specific) The student will understand hypothesized and known etiologies of some important human neurobiological conditions, as well as some neurobiological mechanisms involved in normal functioning; they will do this through reading and actively analyzing and discussing published scientific primary, secondary and review literature. Benchmark 2.a The human nervous system is compartmentalized and that brain regions and nervous system cells have specialized function. Indicator 2.a.1 Students will demonstrate understanding that the healthy operation of the human central nervous system (CNS) requires a variety of cell types and specialized structures. Indicator 2.a.2 Students will demonstrate understanding that the human CNS is regionally specialized with distinct regions of the brain roughly viewed as being hubs for particular processes and activities. 4
Indicator 2.a.3 The CNS adjoins the peripheral nervous system, allowing organisms to sense, process and respond to external stimuli. Indicator 2.a.4 Students will be able to identify at least three human brain regions and the processes with which these regions are associated. Indicator 2.a.5 Students will recognize that neuroscience includes studying both the central and peripheral nervous systems, although the source of many disorders is within the brain itself. Benchmark 2.b Roles and functions of brain structures, tissues and cells are discussed. Indicator 2.b.1 Students will explain the location and function of the blood brain barrier. Indicator 2.b.2 Students will describe the function of endothelial cells, tight junctions, transport proteins and astrocytes, and the contribution each makes to a healthy blood brain barrier. Indicator 2.b.3 Students will explain the four main functions of glial cells in the brain: (1) provide physical support to neurons, (2) supply neurons with nutrients, oxygen and chemical signals to neurons, (3) insulate neurons from each other, and (4) destroy dead neurons and pathogens. Indicator 2.b.4 Students will understand that glial cells form myelin but are distinct from the Schwann cells of the peripheral nervous system which have are tight junctions between them. Indicator 2.b.5 Students will understand that astrocytes (of the blood brain barrier) and oligodendrocytes (of the CNS myelin sheath) are sub-types of glial cells, of which there are several other types. Benchmark 2.c Causation and effects of infection of the central nervous system are addressed. Notably, investigators are focusing intense effort into understanding and treating HIV-associated neurocognitive impairment which has become increasingly prevalent. Antiretroviral therapies may inhibit AIDS infection of CD4 T cells. However, cognitive impairment is becoming a grave problem as infected individuals are living longer but therapies are failing to control the progression of the cognitive dysfunction associated with HIV entry into the brain. Indicator 2.c.1 Students will demonstrate understanding that infection of the brain can occur, despite the high level of protection the blood brain barrier provides. Indicator 2.c.2 Students will describe one way HIV can enter the brain and the general course of disease. Indicator 2.c.3 5
Students will explain why HIV-associated neurocognitive disorder (HAND) has become a pressing biomedical issue. Indicator 2.c.4 Students will describe one current line of research investigating the mechanism of HIV infection within the brain, or its treatment. Benchmark 2.d Effects of impact injury to the brain are discussed. This can occur from both mechanical blows and non-blow air pressure impact, for example. Effective treatments, and the identification of biomarkers for treatment failure and recovery progression, are under investigation for all types of traumatic brain injury (TBI). Scientists are also working to identify biomarkers which indicate the occurrence of non-blow brain injury. Indicator 2.d.1 Students will demonstrate understanding that traumatic injury to the brain is a serious medical issue particularly for sports enthusiasts and military personnel. Indicator 2.d.2 Students will define or describe traumatic brain injury and the possible course of the condition. Indicator 2.d.3 Students will describe the objective of one current line of research regarding the treatment or identification of traumatic brain injury. Benchmark 2.e Common and debilitating human CNS diseases and disorders are discussed. Indicator 2.e.1 Students will demonstrate understanding that mechanisms of heredity affect human neurobiological functioning in complex ways that extend beyond the simple passage of genetic material to offspring. Epigenetic influences, for example, have been found to alter an individual s ability to cope with stressful situations as an adult. Indicator 2.e.2 Students will recognize mechanisms of epigenetic changes, and apply Advanced Placement Biology knowledge during discussions. Indicator 2.e.3 Students will demonstrate understanding that normal human functions such as sleep, navigation, communication, learning and memory, consciousness, and the experience of pain (especially neuropathic) are each under the control of the central nervous system. Disruption of these normal functions can be debilitating or even lethal and is under continued investigation by scientists. Indicator 2.e.4 Students will describe and discuss one neurobiological mechanism currently under investigation which functions in regulation of (each) sleep, navigation, communication, learning and memory, consciousness, and the experience of pain. Indicator 2.e.5 Students will recognize and understand that frequently, the etiology of a CNS disorder is not fully understood, yet treatments still may exist. Indicator 2.e.6 6
Students will demonstrate understanding that the functioning of the human CNS is affected by factors not under neurobiological control, such as the sex of an individual, aging, and exercise, that these factors interact with the nervous system to alter an individual s behavior and cognitive abilities, as well as the course of disease. Indicator 2.e.7 Students will discuss one line of neuroscience research investigating the effect of sex, aging and/or exercise on neurobiological function, conditions, disease and/or processes. Indicator 2.e.8 Students will demonstrate understanding that there are numerous debilitating human CNS disorders/diseases, including and not limited to Alzheimer s disease, addiction, autism, attention deficit disorder, depression, epilepsy, Parkinson s disease and schizophrenia. Indicator 2.e.9 Students will demonstrate understanding that the etiology of each of the disorders (2.e.7) is not fully understood and thus these conditions can have serious negatively impact not only those affected, but also their care-takers. Indicator 2.e.10 Students will understand that these disorders (2.e.7) are under continued investigation by scientists who utilize a multitude of experimental approaches and some scientists focus on studying options for treatment, regardless of the fact that etiologies are not well understood. Indicator 2.e.11 Students will describe one currently hypothesized etiology for each of the following: Alzheimer s disease, addiction, autism, attention deficit disorder, depression, epilepsy, Parkinson s disease and schizophrenia. Indicator 2.e.12 Students will recognize that studying efficacious treatments sometimes helps scientists elucidate the underlying mechanism of a function or disorder. Benchmark 2.f Dysfunction or unusual function of the senses, particularly vision and the phenomenon synesthesia, are discussed. Indicator 2.f.1 Students will demonstrate understanding that while sensory pathways are well-delineated in the peripheral nervous system, in the central nervous system, dysfunctional crosstalk between brain regions can cause a single sensory stimulus to activate more than one sensory experience; this phenomenon is known as synesthesia. Indicator 2.f.2 Students will describe at least one sub-type of synesthesia. Indicator 2.f.3 Students will discuss at least one specific hypothesis and line of research attempting to elucidate the etiology of synesthesia. Indicator 2.f.4 Students will demonstrate understanding that the sense of vision provides a neurobiological model for other senses. 7
Indicator 2.f.5 Students will demonstrate understanding that vision disabilities, specifically, are a serious impediment to normal living and that various causes of blindness and disease are being investigated by scientists, as are various routes of treatment (e.g. stem cell transplant). Indicator 2.f.6 Students will discuss discoveries which have been made during investigations relating to human sight, such as the identification of novel photoreceptors not belonging to either the rods or cones groups, and that there can be unconscious vision (seeing without knowing it). Indicator 2.f.7 Students will discuss one line of research investigating the normal neurobiological functioning of the sense of vision, and/or a current line of research investigating a treatment for blindness or a vision disorder. Benchmark 2.g The neurobiological bases of emotional and other psychological states are discussed. Indicator 2.g.1 Students will demonstrate understanding that emotions and other psychological phenomena such as anxiety, morality, decision-making, love, trust, humor and creativity all have been found to have neural correlates. These amorphous experiences and abilities have their basis in neurobiology. Indicator 2.g.2 Students will understand that neuroscientists study human psychological and/or emotional experiences for many different purposes - to ameliorate dysfunction (e.g. panic disorder) or to better understand how to influence consumer purchasing decisions (neuroeconomics), for example. Indicator 2.g.3 Students will describe one neural mechanism under investigation that explains each of at least four of the following phenomena: anxiety, morality, decision-making, love, trust, humor and creativity. Benchmark 2.h Scientists use a myriad of experimental approaches in neuroscience. Indicator 2.h.1 Students will be able to name and/or describe experimental methods that scientists use in neuroscience (e.g. molecular biology techniques to study gene expression, BOLD to study neural metabolic activity) and discuss their use in (the published) research. Standard 3 (modified from State of VA Biology Std 1; note that standard s 1.a, 1.g, 1.k and 1.l are not included) The student will demonstrate an understanding of scientific reasoning, logic, and the nature of science by performing laboratory activities and planning a potential, viable Neuroscience Senior Research Lab (NRL) investigation. Benchmark 3.a (addition to State of VA Biology Std 1, TJHSST-specific) Non-human living organisms and/or systems are utilized as models to study human conditions or their possible treatments. Indicator 3.a.1 Students will describe the relationship between the model system and humans. 8
Benchmark 3.b Hypotheses and project objectives are formulated based on direct observations and information from scientific literature. Indicator 3.b.1 Students will design an investigation predicated upon, and which references relevant and recent primary research reports, as well as prior related research conducted in the NRL and other labs. Indicator 3.b.2 Students will provide a compelling justification for their investigation by articulating the current scientific or medical problem it helps to solve. Benchmark 3.c (modified from State of VA Biology Std 1.c, TJHSST-specific) Variables and controls are defined and investigations are designed to test hypotheses. Indicator 3.c.1 Students will articulate a testable hypothesis with defined, appropriate controls and variables. Indicator 3.c.2 Students will draw a viable, specific connection (i.e. cause and effect relationship) between the independent and dependent variables. Indicator 3.c.3 Students will propose a satisfactory number of trials for proper statistical analysis and/or level of confidence. Benchmark 3.d Graphing and arithmetic calculations are used as tools in data analysis. Indicator 3.d.1 Students will describe at least one statistical method for analyzing the collected data. Indicator 3.d.2 Students may present representative tables and graphs to display their results. Benchmark 3.e Conclusions are formed based on recorded quantitative and qualitative data. Indicator 3.e.1 Students will describe steps taken to ensure reliability of data, particularly if the study is a behavioral study with a qualitative dependent variable. Indicator 3.e.2 Students will describe data resulting from any simulation and how it will be analyzed in order to determine degree of success. Indicator 3.e.3 Students will describe how the data and its analysis will directly provide evidence to refute or support the experimental hypothesis. Benchmark 3.f (modified from State of VA Biology Std 1.f, TJHSST-specific) 9
Sources of error and limitation inherent in experimental design are identified, discussed and remedied if possible. Indicator 3.f.1 Students will acknowledge, describe and/or discuss important limitations to the experimental design. Indicator 3.f.2 Students will plan an investigation that is feasible in terms of time, NRL resources (e.g. equipment), and money. Indicator 3.f.3 As appropriate, students will make corrections based on feedback from instructors and peers. Benchmark 3.g (addition to State of VA Biology Std 1, TJHSST-specific) Sources of bias in experimental design are identified and discussed. Indicator 3.g.1 Students will discuss the validity or limitations of control conditions utilized. Indicator 3.g.2 Students will use evidence, apply logic, and construct an argument for or against a peer s proposed experimental design and/or methodology. Indicator 3.g.3 Students will recognize that in order to ensure the validity of scientific investigations, they must be evaluated by other members of the scientific community. Benchmark 3.h Chemicals and equipment are used in a safe manner. Indicator 3.h.1 Students will not plan to avoid known hazards which cannot be controlled. Benchmark 3.i (modified from State of VA Biology Std 1.i, TJHSST-specific) Appropriate technology such as computers, imaging technologies (e.g. fluorescent microscope), and that which is used in molecular/cellular biology research (e.g. EEG, electrophysiology) is used for gathering and analyzing data. Indicator 3.i.1 Students will describe the use of technology in the gathering and analysis of data. Benchmark 3.j (modified from State of VA Biology Std 1.i, TJHSST-specific) Appropriate technology such as computers, and graphing and statistical software is used for communicating results, modeling concepts, and simulating experimental conditions. Indicator 3.j.1 Students will present their proposed investigation using technology. Indicator 3.j.2 Students will describe the use of technology for any proposed simulation in an investigation, and they will discuss the perceived robustness of that model. Benchmark 3.k Research utilizes scientific literature. 10
Indicator 3.k.1 Students will design an investigation predicated upon, and which references relevant and recent primary research reports, as well as prior related research conducted in the NRL and other labs. Benchmark 3.l Current applications of biological concepts are used. Indicator 3.l.1 Students will apply their conceptual understandings of biological concepts introduced in Advanced Placement Biology including and not limited to cell signaling events and pathways, regulation of homeostasis, neuronal signaling events, the basis and effect of genetic anomalies, behavior is a phenotype and scientists measure it, etc. Standard 4 (TJHSST-specific) The student will demonstrate an understanding of the current social context in which neuroscience research is occurring. Benchmark 4.a Communicating with both scientific and non-scientific audiences is an essential component of a complete and successful scientific investigation. Scientists must be able to convey complex scientific information to varied communities peers, personnel of funding organizations, the public, etc. Typically, this is a skill that requires development with frequent practice over time. Indicator 4.a.1 Students will participate verbally in each class discussion about scientific articles by asking a question or making a comment requiring comprehension, analysis, evaluation or synthesis skill and which forwards the conversation and enhances the understanding of the experiment at hand for other students. Benchmark 4.b Gaining impartial research funding is a vital part of scientific pursuit. Indicator 4.b.1 Students will demonstrate the understanding that, by its very nature, objectivity is necessary in scientific endeavors. Indicator 4.b.2 Students will recognize that the vast majority of scientific investigations are conducted by academic, philanthropic or government institutions. And, the financial backing for these investigations comes from impartial sources, rather than from sources which could encourage bias or deceit. Benchmark 4.c The justification for a research study arises from the potential for it to advance community-wide understanding and to benefit disabled individuals in the future. Indicator 4.c.1 Students will demonstrate understanding that in order for a scientific investigation to be feasible the perceived benefit of the research must be at least as valuable as the expected cost of the investigation. Benchmark 4.d 11
Breaches in integrity have wide-sweeping and serious effects. Individual scientists sometimes publish false results for personal gain. However, this kind of deceit has wide-sweeping and serious consequences. Often, every professional associate and the institution lose credibility. Offending scientists may be arrested for illegally using Federal funding (at least). Furthermore, there can be significant misappropriation of money and effort in subsequent investigations which are designed to further these (false) results, or that are relying on these false results for justification. Indicator 4.d.1 Students will demonstrate an understanding that there are wide-sweeping and serious effects of breaches in scientific integrity. Benchmark 4.e Ethical elements of conducting studies with human and animal subjects are pertinent and regulated. Indicator 4.e.1 Students will explain the role of the Institutional Animal Care and Use Committee (IACUC). Proposed scientific studies involving warm-blooded vertebrates must obtain approval from the Institutional Animal Care and Use Committee (IACUC) which oversees ethical use of such animals in research. The Animal Welfare Act of 1966 and the Public Health Service provide the main tenants on which IACUC operates. Part of the IACUC s job is to conduct regular inspections of laboratories using such animals as subjects. Indicator 4.e.2 Students will describe the role of the (an) Institutional Review Board (IRB). Proposed scientific studies involving human subjects must obtain approval by the Institutional Review Board (IRB) which conducts a risk-benefits analysis. The priority of the IRB is to protect human subjects from physical or psychological harm. This includes that anonymity of human subjects is ensured, for example, by requiring that lab samples taken for analysis are labeled with scant, predetermined information. In a few, specific situations, there are exceptions to needing IRB approval (e.g. some surveys). Benchmark 4.f Neuroscientists are currently collaborating to create a brain map of neural circuits for use in preventing, treating and/or curing brain disorders that take significant toll on individuals, families and society. Indicator 4.f.1 Students will demonstrate an awareness of the BRAIN initiative, for example, and the collaborative nature of neuroscience research. 12