Foundational Neuroscience Discussion Paper

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Week 1 discussion Discussion: Foundational Neuroscience As a psychiatric mental health nurse practitioner, it is essential for you to have a strong background in foundational neuroscience. In order to diagnose and treat clients, you must not only understand the pathophysiology of psychiatric disorders, but also how medications for these disorders impact the central nervous system. These concepts of foundational neuroscience can be challenging to understand. Therefore, this Discussion is designed to encourage you to think through these concepts, develop a rationale for your thinking, and deepen your understanding by interacting with your colleagues. Foundational Neuroscience Discussion Paper Required Readings Note: All Stahl resources can be accessed through the Walden Library using this link. This link will take you to a log-in page for the Walden Library. Once you log into the library, the Stahl website will appear. Stahl, S. M. (2013). Stahl’s essential psychopharmacology: Neuroscientific basis and practical applications (4th ed.). New York, NY: Cambridge University Press *Preface, pp. ix–x Note: To access the following chapters, click on the Essential Psychopharmacology, 4th ed tab on the Stahl Online website and select the appropriate chapter. Be sure to read all sections on the left navigation bar for each chapter. Chapter 1, “Chemical Neurotransmission” Chapter 2, “Transporters, Receptors, and Enzymes as Targets of Psychopharmacologic Drug Action” Chapter 3, “Ion Channels as Targets of Psychopharmacologic Drug Action” Document: Midterm Exam Study Guide (PDF) Document: Final Exam Study Guide (PDF) Required Media Laureate Education (Producer). (2016i). Introduction to psychopharmacology [Video file]. Baltimore, MD: Author. Note: The approximate length of this media piece is 3 minutes. Accessible player Optional Resources Laureate Education (Producer). (2009). Pathopharmacology: Disorders of the nervous system: Exploring the human brain [Video file]. Baltimore, MD: Author. Note: The approximate length of this media piece is 15 minutes. Dr. Myslinski reviews the structure and function of the human brain. Using human brains, he examines and illustrates the development of the brain and areas impacted by disorders associated with the brain. Accessible player Laureate Education (Producer). (2012). Introduction to advanced pharmacology [Video file]. Baltimore, MD: Author. Note: The approximate length of this media piece is 8 minutes. In this media presentation, Dr. Terry Buttaro, associate professor of practice at Simmons School of Nursing and Health Sciences, discusses the importance of pharmacology for the advanced practice nurse. Accessible player To prepare for this Discussion: Review this week’s Learning Resources. Reflect on concepts of foundational neuroscience. Week 3 discussion Discussion: The Impact of Ethnicity on Antidepressant Therapy Major depressive disorder is one of the most prevalent disorders you will see in clinical practice. Treatment for this disorder, however, can vary greatly depending on client factors, such as ethnicity and culture. As a psychiatric mental health professional, you must understand the influence of these factors to select appropriate psychopharmacologic interventions. For this Discussion, consider how you might assess and treat the individuals in the case studies based on the provided client factors, including ethnicity and culture. Required Readings Note: All Stahl resources can be accessed through the Walden Library using this link. This link will take you to a log-in page for the Walden Library. Once you log into the library, the Stahl website will appear. Stahl, S. M. (2013). Stahl’s essential psychopharmacology: Neuroscientific basis and practical applications (4th ed.). New York, NY: Cambridge University Press. Note: To access the following chapters, click on the Essential Psychopharmacology, 4th ed tab on the Stahl Online website and select the appropriate chapter. Be sure to read all sections on the left navigation bar for each chapter. Chapter 7, “Antidepressants” Stahl, S. M. (2014b). The prescriber’s guide (5th ed.). New York, NY: Cambridge University Press. Note: To access the following medications, click on the The Prescriber’s Guide, 5th ed tab on the Stahl Online website and select the appropriate medication. Review the following medications: amitriptyline bupropion citalopram Foundational Neuroscience Discussion Paper

Neuroscience is the scientific study of the nervous system.[1] Traditionally, neuroscience has been seen as a branch of biology. However, it is currently an interdisciplinary science that collaborates with other fields such as chemistry, computer science, engineering, linguistics, mathematics, medicine and allied disciplines, philosophy, physics, and psychology. It also exerts influence on other fields, such as neuroeducation[2] and neurolaw. The term neurobiology is usually used interchangeably with the term neuroscience, although the former refers specifically to the biology of the nervous system, whereas the latter refers to the entire science of the nervous system.Foundational Neuroscience Discussion Paper
The scope of neuroscience has broadened to include different approaches used to study the molecular, cellular, developmental, structural, functional, evolutionary, computational, and medical aspects of the nervous system. The techniques used by neuroscientists have also expanded enormously, from molecular and cellular studies of individual nerve cells to imaging of sensory and motor tasks in the brain. Recent theoretical advances in neuroscience have also been aided by the study of neural networks.
Because of the increasing number of scientists who study the nervous system, several prominent neuroscience organizations have been formed to provide a forum to all neuroscientists and educators. For example, the International Brain Research Organization was founded in 1960,[3] the International Society for Neurochemistry in 1963,[4] the European Brain and Behaviour Society in 1968,[5] and the Society for Neuroscience in 1969.[6]
Neuroscience is the scientific study of the nervous system.[1] Traditionally, neuroscience has been seen as a branch of biology. However, it is currently an interdisciplinary science that collaborates with other fields such as chemistry, computer science, engineering, linguistics, mathematics, medicine and allied disciplines, philosophy, physics, and psychology. It also exerts influence on other fields, such as neuroeducation[2] and neurolaw. The term neurobiology is usually used interchangeably with the term neuroscience, although the former refers specifically to the biology of the nervous system, whereas the latter refers to the entire science of the nervous system.Foundational Neuroscience Discussion Paper
The scope of neuroscience has broadened to include different approaches used to study the molecular, cellular, developmental, structural, functional, evolutionary, computational, and medical aspects of the nervous system. The techniques used by neuroscientists have also expanded enormously, from molecular and cellular studies of individual nerve cells to imaging of sensory and motor tasks in the brain. Recent theoretical advances in neuroscience have also been aided by the study of neural networks.

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Modern medicine has worked miracles: we have cured infectious diseases with vaccines, replaced failing organs with transplants, converted many cancers from death sentences into treatable conditions. But one area has lagged far behind the others: the brain. Psychiatric illnesses are some of the most widespread and poorly treated conditions. The problem? Our treatments are too broad. We have many drugs to treat psychiatric diseases, but instead of just adjusting the activity of certain neurons in an affected region, they change the function of the entire nervous system. The consequence? A laundry list of harmful side effects. Thus, finding new, precise ways to treat psychiatric disease is a critical endeavor.Foundational Neuroscience Discussion Paper

Fortunately, tools for better psychiatric treatment already exist thanks to an ongoing revolution in basic neuroscience research. Two technologies in particular have transformed our ability to precisely manipulate neurons: optogenetics and chemogenetics. In optogenetics, light- sensitive molecules, known as opsins, are inserted into the cell membranes of a given population of neurons. These opsins are ion channels that open in response to light and thereby enhance or suppress the electrical activity of neurons. By applying laser light to the neurons expressing the opsins, you can rapidly alter the cells’ electrical activity. Scientists have used this method to control a variety of animal behaviors such as eating, sleeping, learning, mood. One major shortcoming of optogenetics is the need for a fiber optic cannula or a cranial window in the skull to deliver laser light. A potential solution that could bring optogenetics closer to the clinic is the use of red-shifted opsins, which are activated by a lower energy laser that scatters less when traveling through tissue, allowing light delivery external to the skull (1).Foundational Neuroscience Discussion Paper

Chemogenetics employs a similar strategy to optogenetics, but it replaces light with a more traditional activator—drugs. The most popular variant of chemogenetics is DREADDs: designer receptors exclusively activated by designer drugs. DREADDs were developed by altering existing cell membrane receptors so that they instead respond to a designer drug, clozapine N-oxide (CNO). CNO was selected because it is otherwise inert in rodents, so no matter where the CNO is administered it can only produce an effect at its designer receptor. Like opsins, DREADDs can excite or inhibit the electrical activity of neurons, depending on the receptor from which the DREADD is derived. The DREADDs can be activated at any time by administering CNO as you would any other drug.Foundational Neuroscience Discussion Paper

The key advancement of chemogenetics over standard pharmacological treatment is the ability to restrict DREADD expression, and thus CNO’s effect, to a specific population of cells using a combination viral genetic technique. DREADDs are delivered to a region of interest via intracranial infusion of an adeno-associated virus (AAV). These viruses are capable of infecting cells, but they have been robbed of their ability to replicate, preventing harmful spread. Scientists can alter the DNA sequence of the virus to contain different gene and promoter combinations.
The gene determines the protein product, DREADDs in this case, and the promoter region determines which cells can initiate transcription of that gene. For example, the promoter region for agouti-related peptide (AgRP), a signaling molecule that increases appetite, would cause DREADDs to be expressed only in cells that also produce AgRP.Foundational Neuroscience Discussion Paper

One group of researchers used that very approach to investigate how the activity of AgRP-producing cells in the arcuate nucleus control eating (2). They found that after injecting an excitatory DREADD into the arcuate nucleus, the administration of the designer drug CNO caused an increase in food consumption. When an inhibitory DREADD was used instead, the mice ate less. The study provided some of the first evidence for the role of these neurons in controlling feeding behavior. Many additional studies have successfully used DREADDs to demonstrate the importance of distinct cell populations in previously uncharacterized behaviors. One group of scientists used DREADDs to investigate the role of the suprachiasmatic nucleus (SCN) in controlling the circadian rhythm, which regulates cycles of sleep and activity (3). Remarkably, the researchers could reprogram the circadian clock just by activating a small population of SCN cells. Another study sought to understand the mechanisms in the hippocampus underlying the formation of fearful memories (4). By inhibiting certain cells in the hippocampus, the researchers could prevent the formation of the contextual fear memories so detrimental to post-traumatic stress disorder patients.Foundational Neuroscience Discussion Paper

These studies are just a small sample of the many discoveries DREADDs have afforded. Their findings have not only enhanced our knowledge of the brain; they provide new approaches to treat conditions that have few efficacious treatments. The most common prescriptions for PTSD, for instance, are selective serotonin reuptake inhibitors (SSRIs). SSRIs act by increasing the amount of the chemical messenger serotonin throughout the entire nervous system. Such a broad effect explains why SSRIs have numerous side effects, including sexual dysfunction, nausea, and insomnia. Treating PTSD with DREADDs would avoid all of these complications because the drug would only have an effect on the group of neurons involved in the fearful memories.Foundational Neuroscience Discussion Paper

Two barriers remain between DREADDs and the clinic. Injecting the DREADD-containing AAV requires intracranial surgery, restricting recipients to the neediest. But there is precedent for successful use of AAV in humans: a 2007 clinical trial improved movement impairment in Parkinson’s Disease patients (5). The other consideration is the designer drug. Although CNO is inert in rodents, the human body occasionally converts it to clozapine, an antipsychotic drug. One alternative is the drug perlapine, which is approved in Japan for the treatment of insomnia. It has a very high affinity for DREADDs, so at small doses it could activate the receptors without risk of off-target effects(6). Because it is already approved for use in humans, perlapine may be the best bet for a DREADD clinical trial. These obstacles are only temporary and pale in comparison to the promise DREADDs hold for treating psychiatric illness. We must now harness the level of precision DREADDs and optogenetics provide to develop better psychiatric treatments.Foundational Neuroscience Discussion Paper