John Stead, PhD, Associate Professor, Department of Neuroscience, Carleton University
Alex Wiseman, B.Sc., Department of Neuroscience, Carleton University
Kim Hellemans, PhD, Chair, Instructor III, Department of Neuroscience, Carleton University
What is Neuroscience?
Neuroscience is a highly interdisciplinary science that explores the relationship between the nervous system, behaviour, cognition, and disease. While the study of the nervous system harkens back to Egyptian times, modern neuroscience combines aspects of physiology, anatomy, psychology, biology, and mathematics to explore how the nervous system works at the cellular, molecular, cognitive, and societal level (Squire et al., 2012). Broadly, neuroscientists are interested in understanding how cells in the brain (primarily neurons and glia) communicate with one another, how they are organized to form circuits, how external and internal stimuli influence these circuits, and how they might go awry in the context of disease or trauma. Recent technological innovations in the 20th century with regard to both molecular biological and neuroimaging techniques have led to significant advancements in our understanding of brain function. However, despite these advances, exactly how the brain combines external and internal signals to create a perceptual reality remains elusive.
The last 50 years has seen a massive increase in Neuroscience research, incorporating expertise from a wide range of scientific disciplines. To begin to understand the current state of neuroscience, it is useful to briefly review some of the major milestones across the history of research into the nervous system.
History of Neuroscience: Significant Scholarly Findings
The study of the brain dates back through millennia (see Kandel, Schwartz, Jessell, Siegelbaum, & Hudspeth, 2013). The earliest written record referring to the brain dates from the 17th century BC, with an Ancient Egyptian medical text called the Edwin Smith Papyrus, which describes the symptoms associated with head injuries in two patients. Early descriptions of basic neuroanatomy have been found in Egyptian texts from the 3rd and 4th centuries BC, including reference to the cerebrum, cerebellum and ventricles. The idea that the brain was the physical location of the mind was suggested as early as the 5th century BC by the Greek philosophers Alcmaeon of Croton and Hippocrates. This relationship between brain and mind was not universally accepted however, with Aristotle (4th century BC) believing that the brain acted to cool the blood, with intelligence instead located in the heart. The importance of the relationship between the brain and body was highlighted by the Roman physician Galen in the 2nd century AD, who correctly identified 7 of the 12 cranial nerves, proposing that these nerves carry fluid from the brain towards the rest of the body. While further detailed characterization of the anatomy of the central nervous system would take place over the next 1500 years, including the contributions in 14th century by de Luzzi and da Vigevano, in the 15th-16th century by da Vinci, Vesalius and in the 17th century by Willis, substantial advancements in understanding the detailed functionality of nervous tissue would not be seen until the late 18th century.
18th to mid-19th century
Luigi Galvani (1737–1798) was an Italian physician who first discovered the link between electricity and activity of the body. By applying static electricity to a nerve in the leg of a dissected frog he revealed that electrical stimulation could produce contraction of the leg muscles. These experiments represent the origin of the discipline of electrophysiology. Demonstration that the brain and not the heart was the physical location of the ‘mind’ was not achieved until the 19th century, in part through the work of the French physiologist Jean Pierre Flourens (1794-1867). Working with rabbits and pigeons, Flourens lesioned areas of the brain and found impairments in sensory and motor skills. His work however was consistent with the prevailing view at that time that the brain was a unitary and indivisible organ, and that specific functions were not localized to specific brain areas. This view was ultimately challenged by explorations of linguistic deficiencies in humans. In the mid-19th century, the French neurologist Paul Broca described a patient who has suffered stroke resulting in specific impairments in his ability to speak, although his ability to understand language was seemingly unaffected. Following the death of the patient, Broca undertook a post-mortem examination and identified a specific region of the left frontal lobe that was damaged. Further studies of a total of eight similar individuals with similar impairments and similar patterns of damage led Broca to the conclusion that specific functions, such as language, are associated with specific areas of the brain.
LATE 19th CENTURY
A few decades later, work from the Italian biologist Camillo Golgi (1843-1926) would produce a watershed in our conceptualization of the organization of tissue in the brain. In the 1870s, Golgi invented a procedure for staining brain tissue with silver chromate salts. This technique, still widely used today, has the remarkable effect of completely staining a small subset (1-5%) of neurons in the brain. There is still no clear explanation for why some cells take up this stain while others do not. This technique was employed extensively by Santiago Ramón y Cajal beginning in 1887, allowing him to detail the shapes of hundreds of individual neurons across many different parts of the brain. This led Cajal to various conclusions including that brain tissue was a network of individual cells, with individual cells varying dramatically in their shapes and complexities depending on their location within the brain. Despite this morphological variability, neurons all seemed to have a cell body to which were connected two types of process, with many branching dendrites providing the input to the neuron, and a single axon providing the output from the neuron. These observations were used by Cajal to strongly support the neuron doctrine, that the neuron is the fundamental unit of signalling in nervous systems. Golgi and Cajal were awarded the Nobel Prize in Physiology or Medicine in 1906, for their pioneering contributions to understanding of the fine anatomy and organization of neural tissue. The legacy of these early microscopic anatomical studies is still clearly visible in neuroscience textbooks today, most of which still carry drawings of cells made by Golgi or Cajal, and invariably include images of Golgi-stained cells.
In the late 19th century, Emil du Bois-Reymond, Johannes Peter Müller, and Hermann von Helmholtz demonstrated that these neurons were electrically excitable and were therefore likely to be the cells carrying those signals that were first identified by Galvani. Furthermore, they found that electrically excited neurons were able to create changes in the electrical states of other nearby neurons.
20th to early 21st Century
The question of exactly what caused the transmission of electrical activity from one neuron to another was finally answered in 1921 by the German pharmacologist Otto Loewi (1873-1961). In what has become a very famous experiment, Loewi took a frog heart which was bathed in a saline solution and electrically stimulated it via the vagus nerve, causing the heart to beat more slowly. He then took some of the surrounding solution and applied it to a second heart that had not been electrically stimulated and found that this caused the second heart to also beat more slowly. He concluded that electrical stimulation of the heart caused the release of a chemical into solution, and this chemical by itself was sufficient to stimulate the second heart to beat more slowly. The chemical was later identified as acetylcholine, which was the first of many neurotransmitters that would ultimately be identified. For this research, Loewi was awarded the Nobel Prize in Physiology or Medicine in 1936, together with Sir Henry Dale who was able to demonstrate that the active chemical from Leowi’s experiments was indeed acetylcholine. Subsequent work by Sherrington found that these chemical messengers were usually released at small specialized structures called synapses, where chemical messages allowed one neuron to either excite or inhibit another; research for which Sherrington was awarded the Nobel in 1932.
By the 1930s, an emerging picture of the central nervous system had thus been established. The brain was the physical location of the mind, and controlled thought, sensation and movement. Brain tissue was composed of individual neurons each of which had an input and an output. Information was transmitted along neurons in the form of electrical impulses, with intercellular communication mediated by chemical messengers which we now call neurotransmitters. The last century has built upon this foundation with extraordinarily rapid advances in our understanding of the nervous system. Any summary of these advances will by its nature be very incomplete. We here choose to review progress by focusing exclusively on those neuroscientists whose research has been awarded the Nobel Prize in Physiology or Medicine. Names and dates of Nobel prize awards are indicated in parentheses below after “NP”. See www.nobelprize.org for all awards.
The 20th century saw enormous advances in our understanding of neuronal communication, both in terms of how information is transmitted along an individual cell, and also between different cells. New techniques that allowed visualization and recording of electrical signals were developed in the 1920, and different neurons were shown to transmit electrical signals at different speeds, depending on the thickness of the neuron (NP: Erlanger & Gasser, 1944). These tools led to an elegant series of experiments by Hodgkin and Huxley that elucidated the molecular basis of electrical signaling. Using the giant axon of the squid they were able to record electrical potential across the neuronal membrane. By manipulating the ionic solution in which the neuron was bathed, and the electrical potential across the membrane, while recording the magnitude of current flowing across the membrane, they developed a model of how an electrical impulse is produced and propagated along neuronal axons, mediated by the flow of different types of charged ions both along and through the membrane. Eccles extended these findings by describing how electrical activity at the synapse could lead to excitation or inhibition of adjacent cells (NP: Eccles, Hodgkin Huxley, 1963). Elucidation of the properties of individual ion channels that underlie changes in electrical currents across neuronal membranes was finally achieved through development of the patch-clamp technique, which allowed recording of electrical activity across microscopically small areas of cell membranes (NP: Neher & Sakmann, 1991).
In parallel with the detailed characterization of electrical properties of neurons, other neuroscientists were focused on understanding the basis of the chemical signals that mediated communication between neurons at the synapse. Building upon the earlier work of Loewi and Dale which identified acetylcholine as the first neurotransmitter, von Euler and Axelrood described a second neurotransmitter norepinephrine, which functioned (in part) to regulate blood pressure, and made the important observation that some antidepressants acted by blocking the reuptake of the neurotransmitter at the synapse. Katz demonstrated that neurotransmitters were stored in small vesicles in one neuron, with vesicles released into the synapse following electrical stimulation, in a mechanism that required changes in intracellular calcium signalling (NP: Katz, von Euler, Axelrod, 1970). The complex process of vesicle release was carefully elucidated by Südhof, Rothman, Schekman (NP: 2013). Many additional neurotransmitters were also identified by other researchers including dopamine, the deficiency of which was associated with Parkinson’s disease, leading to novel therapies for the disorder. Synaptic signalling was further refined with an understanding that while some neurotransmitters result in electrical changes in target cells, others change the chemical signalling environment of their targets, including mediating changes in synaptic strength as a form of learning and memory (NP: Carlsson, Greengard, Kandel, 2000).
The above studies describe how signals move along neurons, and between closely adjacent neurons. However, signals can also be transmitted across much larger distances, in some cases by hormones that are released by the brain and that act on neuronal and non-neuronal targets throughout the body. Guillemin and Schally identified the specific factors that were released by the brain that cause the release of hormones from the pituitary gland at the base of the brain. To allow the effects of such hormones to be characterized, Rosalyn Yalow developed a technique that combined radioactive isotopes with highly specific antibodies to track levels of such hormones in the body (NP: Guillemin, Schally, & Yalow, 1977). In addition to hormones released by the brain acting on non-neuronal tissue, extensive work characterized the effect of other factors released by non-neuronal tissue on the brain. For example, Levi-Montalcini identified nerve growth factor (NGF) – a substance isolated from tumours in mice that would cause growth of the nervous system in chick embryos. This formed the basis of detailed characterization of the role of various growth factors in the development and adaptation of the nervous system (NP: Cohen & Levi-Montalcini, 1986).
Beyond understanding the functionality of individual molecules and cells of the nervous system, other neuroscience pioneers explored various systems, including sensory systems by which the brain receives information from the outside world, and motor systems by which the brain acts on and interacts with the outside world. As an example of motor systems, early work on anesthetized cats revealed that weak electrical stimulation of the hypothalamic region of the brain could produce complex behavioural responses including both defensive and aggressive behaviours (NP: Hess & Moniz, 1949). For sensory systems, Nobel prizes have been awarded for the elucidation of both visual and olfactory systems. Collectively, Granit, Hartline and Wald pioneered research that enhanced our understanding of the operation of the retina, including characterizing chemical changes that resulted from exposure to photons of light, the presence of different types of photosensitive cells resulting in colour vision, and how signals received by nearby retinal cells are compared within the retina to highlight contrasts in our visual fields (NP: Granit, Hartline, & Wald, 1967). In the following decades, Hubel and Wiesel explored how these retinal signals were then processed by the brain, with separate processing streams focused on different aspects of the visual input such as movement, contrast, and linear orientation (NP: Hubel & Wiesel, 1981). Research on the olfactory system was awarded the Nobel in 2004, for research demonstrating that the rich diversity of smells that are detectable are the result of the combined actions of hundreds of different chemical receptors called olfactory receptors, which in turn are the product of hundreds of different olfactory receptor genes. Individual smells are the result of the combined signalling of different odorants across a wide spectrum of different receptors (NP: Axel & Buck, 2004).
Other advances of the last century that led to receipt of the Nobel Prize include an understanding of functional differences between the left and right hemispheres of the brain (NP: Sperry, 1981), characterization of prions as agents of infectious disease (NP: Blumberg & Gajdusek, 1976; NP: Prusiner, 1997), and an understanding of how specific cells (termed place cells and grid cells) in the hippocampus and nearby entorhinal cortex contribute to the brain developing an internal map of the surrounding environment, and one’s location within that environment (NP: O’Keefe, Moser, & Moser, 2014).
The above description of neuroscience advances represents the research of a small number of exceptionally talented and celebrated neuroscientists, and of course represents a small fraction of the research output for the discipline. For example, each year, >20,000 neuroscientists meet at the annual Society for Neuroscience conference to discuss their recent finding and celebrate our discipline. While much of the research is not considered directly applied, basic research can potentially lead to various societal changes, both in the present and anticipated for the future.
Branches of Neuroscience
Modern neuroscience can be broadly organized into several major branches:
1) Cellular and Molecular neuroscience
2) Systems Neuroscience
3) Cognitive and Behavioural Neuroscience
4) Social and Translational Neuroscience.
Cellular and Molecular Neuroscience
Cellular and Molecular neuroscientists are focused on understanding how cells of the nervous system express and respond to molecular signals. These scientists typically employ techniques and concepts of molecular biology to study how the brain develops, how cells communicate with one another, how genes and the environment might influence these processes, and how the brain can change and adapt (“neuroplasticity”) over the course of one’s lifetime.
Systems Neuroscience is a branch of neuroscience focused on understanding how different cell groups in the nervous system work together to create circuits, or pathways that have a functional outcome. For example, a systems neuroscientist might ask how specific anatomical regions and/or cell groups are involved in the higher order cognitive processes of learning and memory, or sensory functions such as vision. One branch of systems neuroscience is neuroethology, which involves the study of non-human model organisms to explore how certain sensory or cognitive functions exist in other species. By contrast, neuropsychologists explore how specific neural substrates may be implicated in human behaviour (and how damage to specific brain regions may yield unique deficits in cognition or behaviour).
Cognitive neuroscience is the third major Neuroscience branch and emerged out the fields of psychology and computer science. Cognitive neuroscientists are interested in understanding how specific brain circuits may relate to higher order psychological functions such as learning and memory, language, and thought. The field of cognitive neuroscience has benefited greatly from advances in neuroimaging techniques such as functional magnetic resonance imaging (fMRI), positron emission tomography (PET) and diffusion tensor imaging (DTI), in addition to electroencephalography (EEG). Behavioural neuroscientists (also known as physiological or biological psychologists) employ basic techniques of biology and chemistry to study the function of the nervous system, with a specific application to how cells and cell circuits relate to all aspects of behaviour. Most of the experimental literature has employed model organisms such as rodents or non-human primates, with more recent research using molecular biological techniques to explore how genes and/or epigenetics may modulate behaviour.
Social and Translational Neuroscience
Social and translational neuroscience are the most recently developed fields of neuroscience. Social neuroscience borrows heavily from social psychology and seeks to understand how specific brain substrates, circuits, signals, and / or genes are related to behaviour, with an emphasis on domains of social behaviour. As humans are primarily a social species, this field has a focus on how higher order cognitive domains such as language and thought, as well as pathological conditions such as depression, may influence, and be influenced by, social behaviour. Related to social neuroscience, translational neuroscience is a field of study which translates study and knowledge of neuroscience to clinical applications. Translational neuroscientists are interested in applying technological advances in the field of neuroscience to address various societal needs, including novel treatments or therapies for neurological and psychiatric disease.
Methods in Neuroscience
Neuroscientists working within each of the major branches would typically apply a different set of techniques to answer questions about the brain (See Table 1 for a summary of some of the more common techniques). For example, while neuroscientists in general may be concerned with determining the neural basis for clinical depression, molecular-, systems-, cognitive-, and social-neuroscientists will employ differing techniques and methods to explore how proteins, cells, circuits, and brain regions may each be implicated in the aetiology of the disease.
Cellular and Molecular Neuroscience
A molecular neuroscientist may focus heavily on the application of molecular biology to the nervous system to answer questions regarding the pathophysiology of depression. For instance, they might be interested in identifying key changes in gene expression that are associated with depressive symptoms. This could be achieved by analysing expression levels of thousands of genes in various regions of the human brain using post-mortem tissues derived from individuals with and without depression. If the expression level of a specific gene was consistently higher or lower in the brains of depression patients compared with controls, that suggests that the gene may have a functional role in depression. These genetic profiles can also give us hints as to which proteins may be increased or decreased, and in which specific area of the brain. Furthermore, finding a biomarker that strongly correlates with depression has high diagnostic value in research and in medicine – a biomarker is an easily detectable molecule in our body that is correlated with, and used to predict the presence of disease, infection, symptom, or toxic exposure. To be useful, the biomarker must be detectable in tissues that can be easily obtained from patients (typically saliva, urine or blood). There are extensive interactions between the central nervous system and the periphery – our bodies can tell us numerous things about our brains. As such, a molecular neuroscientist might be interested in searching tissues outside of the central nervous system for candidate biomarkers for the diagnosis of depression.
A major component of molecular neuroscience involves the manipulation of genes within model organisms (rats, mice, zebrafish) in order to understand the function of that gene, including potential functions in the development of disease. Manipulations include changing the amount of gene product, changing the timing or location of gene expression, or changing the actual protein product that is generated by the gene. Molecular neuroscientists might therefore be interested in studying one of the differentially expressed genes identified through gene expression studies. Potential research questions might include, “What is the importance of this gene during development?”, “If we restore this gene back to ‘normal’ levels, what does it do to depressive-like symptoms?”, or “If we change gene expression levels in a similar manner to those that were observed in gene expression studies, does it induce depressive-like behaviours?”. Answering these questions requires the genetic engineering of non-human animals, a technique which had grown in prevalence over the last two decades as the technology becomes increasingly sophisticated, reliable and affordable.
While genetic manipulations can alter the amount, location, or sequence of a protein, there are other methods for manipulating protein functions within cells. Pharmacological manipulations can include the use of competitive agonists (which activate proteins), competitive antagonists (which inactivate proteins), and neutralizing antibodies that interfere with the ability of specific molecules to bind to their specific receptors. Whether by genetic-engineering, or pharmacological manipulation, molecular neuroscientists are concerned with the molecular and cellular changes that underpin diseases. Other techniques in the arsenal of the molecular neuroscientist include using radiolabelled tracers to visualize, in real-time, the movement of neurotransmitter-containing vesicles down an axon. Use of fluorescent or bioluminescent markers to visualize specific interactions between individual molecules (the fluorescence resonance energy transfer [FRET] or bioluminescence resonance energy transfer [BRET] techniques), such as for measuring the recruitment of receptors to the membrane, the coupling of a ligand to its receptor, the coupling of two or more receptors, and the change in conformation of an existing receptor. Researchers use microdialysis to measure the concentration of a specific molecule in the synapse between two neurons or use retrograde and anterograde tracers to determine the physical pathways linking one neuron to another. Ultimately, cellular and molecular neuroscientists interested in depression might employ a broad range of tools to understand how proteins and cells are implicated in disease, and whether these changes may represent either the cause or consequence of the disorder.
Questions about individual cells and molecules may also be of interest to a systems neuroscientist, but they would typically be exploring how cells and molecules modulate the function of brain regions, or circuits composed of multiple anatomical and functional components. One example to illustrate the systems neuroscience approach would be to investigate the hypothalamic-pituitary-adrenal (HPA) axis, which regulates the release of the stress hormone cortisol in humans (corticosterone in rodents) and has been heavily implicated in the aetiology of depression. Release of the stress hormone is mediated by a cascade of signalling factors released from various organs including the brain and regulated in a manner that involves multiple different brain regions. As an example, a systems neuroscientist might explore signalling interactions between the hippocampus and the hypothalamus (the hippocampus senses levels of stress hormone and suppresses any further release of the hormone from the hypothalamus). To that end, they may manipulate hippocampal function in one of many possible ways (including through using a transgenic animal model, or ablation, or by stereotaxic delivery of a drug to the hippocampus, or through electrical stimulation; see table 1 for details) and measure consequent changes in hypothalamic hormone release. This could be followed by post-mortem analyses of brain tissues by immunohistochemistry to determine whether patterns or levels of expression of specific proteins has altered in several interconnected brain regions. In the context of depressive disorders, any or all the above could be explored in the context of how these manipulations also impact depressive symptoms in model organisms.
Cognitive and Behavioural Neuroscience
In the study of depression, a cognitive neuroscientist could ask questions regarding how depression might affect activity levels of different regions of the brain, by for example using imaging techniques to search for changes in metabolic processes of specific brain regions between depressed patients and healthy controls. Cognitive neuroscientists heavily rely on modern neuroimaging techniques such as functional magnetic resonance imaging (fMRI, to measure cerebral blood flow), or positron emission tomography (PET, to measure the metabolism of glucose within brain regions). While MRI technologies have been used in diagnostic medicine since the 1970s, novel analysis of MRI sequences using specialized software developed by computer scientists allows for alternative forms of MRI such as diffusion tensor imaging (DTI) which allows high resolution mapping of the major connections that link and allow communication between different regions of the brain.
Electroencephalography (EEG) is another technique that can be used to measure the electrical activity of the brain. EEGs are an inexpensive means of measuring brain activity in awake humans. A cognitive neuroscientist might use EEG to explore differences in the patterns of electrical activity between depressed individuals and healthy controls while they are engaged in specific cognitive tasks that are designed to assess processes such as attention, inference, reaction time, working memory, or cognitive flexibility.
Behavioural neuroscience, wherein researchers are concerned primarily with physiological, genetic, and developmental mechanisms of behaviour, investigates the influence depression has on behaviour, and often involves use of animal models (such as rodents or zebrafish). Animal models could be generated by various methods including selective breeding for a desired trait (such as anxiety or aggression), by genetic mutation (such as metabolic diseases), or conditioning an animal to elicit a desired behaviour (such as social defeat paradigms and the production of a socially anxious animal). Behavioural neuroscientists have developed a wide array of behavioural paradigms to explore different aspects of depressive-like behaviour including measures of learned helplessness (to model despair), sucrose preference (to model hedonic feeding), food intake, or locomotor activity.
Social and Translational Neuroscience
Social neuroscientists are fundamentally interested in how the brain mediates social interaction; behaviours that are meaningful, elicited by one individual agency, directed towards another individual agency, and receive a response. Most applicable to depression, social neuroscience could explore how social behaviours such as work-place deviance manifest in the neurological condition. Alternatively, social neuroscientists might be interested in how specific gene polymorphisms influence individual vulnerability to depression following exposure to bullying – both in humans or non-human animals.
Translational neuroscientists apply basic neuroscientific research relating to structure and function of the brain in a clinical setting. For example, basic research might indicate that cerebral stimulation has a significant positive effect on depression. A translational neuroscientist might thus investigate the use of a transcranial magnetic stimulator (TMS) as a viable means for brain stimulation to decrease depressive symptoms, and determine the precise stimulation procedure (electrical frequency, duration, etc.) that generates the best results in patients. Alternatively, translational neuroscientists might explore new pharmaceutical drugs for the treatment of psychiatric or neurological disease, determining appropriate dose and duration of the drug to maximize efficacy. Neurorehabilitation is another area encompassed in translational neuroscience, wherein researchers develop, test, and optimize sensory prostheses for the implantation into humans suffering from sensory loss.
Animal Ethics in Neuroscience Research.
The use of animals in experimental research has always been a point of controversy. However, the use of animals in research is highly regulated, with usage most carefully controlled for animals with higher sentience (primates, then other mammals, then other vertebrates and certain molluscs). As such, research that induces suffering in any capacity (e.g., pain, adverse changes in psychological states, stress) must be stringently justified, and will often not be approved. That is, the expected benefits from the proposed research must outweigh the potential suffering of the animal. Governing the subjective nature of such decision-making is an institutional animal care committee composed of both scientists and members of the non-scientific community that decides whether or not the research merits the use of animals. In Canada, the federal government does not have jurisdiction to legislate animal experimentation but does exert influence through the Criminal Code of Canada, Health of Animals Act (1990), and the Canadian Food Inspection Agency. In order for institutions to be federally funded for animal research they must receive accreditation from the Canadian Council on Animal Care (CCAC), which is the national peer-reviewed organization that oversees and implements standards for animal ethics and care. Institutions that are accredited are eligible to receive funding from federal granting agencies, such as Natural Sciences and Engineering Research Council (NSERC) Canadian Institute for Health Research (CIHR), and the Social Sciences and Humanities Research Council of Canada (SSHRC). In addition, provinces in Canada have legislated their own animal-welfare protection acts, and similarly operate provincial-level regulatory agencies similar to the national CCAC body. Because of such system, each research project that includes the use of animals must first have their proposal approved by their institutions committee, and such proposals must abide by the standards set out by the CCAC.
|Name of the technique||Description/Purpose of the technique|
|Imaging and Microscopy|
|Magnetic resonance imaging (MRI)||Use of strong magnetic fields and electrical currents to visualize brain structure in a non-invasive manner|
|Functional magnetic resonance imaging (fMRI)||Form of MRI that measures changes in blood flow to brain regions, from which localized brain activity can be inferred|
|Diffusion tensor MRI||Form of MRI that reveals major pathways of communication between regions of the brain|
|Computerized tomography (CT)||Use of X-rays to visualize brain structure in a non-invasive manner|
|Cerebral angiogram||Use of X-rays and an injected iodine tracer to visualize blood vessels in brain|
|Positron emission tomography (PET)||Use of injected radioactive tracers combined with imaging techniques to measure metabolic activity in brain|
|Electroencephalography||Use of external electrodes on the scalp to measure electrical activity of the cortex|
|Light microscopy||Visualize microscopic brain structure (i.e., neurons, glia)|
|Fluorescence microscopy||Visualize microscopic brain structures that have been tagged with a fluorescent marker, allowing the location of specific known molecules to be seen|
|Electron microscopy||Visualize microscopic brain structures at considerably higher magnification than is possible through light microscopy|
|Rodent behavioural paradigms|
|Rotarod||Measure of coordinated movement|
|Vertical pole test||Measure of balance|
|Visual cliff assay||Measure of visual acuity|
|Morris water maze||Measure of cue-associated spatial learning and memory|
|Radial arm maze||Measure of spatial learning and memory|
|Novel object recognition||Measure of non-spatial learning and memory|
|Social approach/avoidance||Measure of social behaviours|
|Open field test||Measure of anxious behaviour|
|Elevated plus maze||Measure of anxious behaviour|
|Forced swim test||Measure of disparity|
|Tail suspension assay||Measure of learned helplessness|
|Sucrose preference test||Measure of anhedonia|
|Stereotaxic surgery||Surgery that reproducibly targets a very specific region of the brain|
|Cannulation||Introduction of a cannula into a specific region of the brain to allow for controlled delivery of drug or electrode|
|Microdialysis||Continuously samples extracellular fluid from the brain allowing concentration of specific molecules to be determined in real time|
|Ablation||Removal/destruction of a specific brain region to investigate normal function of that region|
|Manipulation of cells and tissues|
|Cell culture||Living cells are grown in vitro, allowing various manipulations to be tested in controlled living systems|
|Electrophysiology||Use of electrodes placed on or in cells to manipulate and record electrical activity, to explore factors that affect excitability of neurons|
|In situ hybridization||Labelled nucleic acid sequences are used to visualize the location and concentration of RNA molecules generated from specific genes|
|Immunohistochemistry||Labelled antibodies are used to visualize the location and concentration of specific proteins in slices of tissue|
|Immunocytochemistry||Labelled antibodies are used to visualize the location and concentration of specific proteins in cells|
|Anterograde and retrograde tracers||Use of chemicals that travel along cells in the same direction or opposite direction compared to the flow of information, in order to determine anatomical connections between cells|
|Molecular biology, genetics and genomics|
|Southern/Northern/Western blots||Semi-quantitative methods to detect specific molecules of DNA/RNA/proteins|
|Immunoprecipitation||Use of an antibody to precipitate a specific protein out of solution, concentrating the solution, and potentially identifying other molecules to which the target protein binds|
|Enzyme-linked immunosorbent assay||Detection and quantification of peptides, proteins, hormone, and antibodies|
|Selective breeding paradigms||Selectively breeding animals over many generations to enrich for genetic variants that may underlie specific traits|
|Genetic modification of animals||Model organisms have specific genes modified, inserted, or removed, in order to determine the function of the gene|
|Viral vector-mediated gene transfer||Use of viruses modified to contain specific genetic sequences, in order to introduce gene expression changes into animal tissues|
|Optogenetics||Insertion of light-sensitive receptor into membrane of neurons. Give experiment control over neuron excitation/inhibition|
|Genome-wide association studies (GWAS)||Analysis of DNA variation across the genome to screen for genes that associate with specific diseases or characteristics|
|Whole genome sequencing||Sequencing of the entire genome to screen for mutations, or genetic variations that associate with specific diseases or characteristics|
|Bisulphite sequencing||Modified DNA sequencing paradigm used to detect epigenetic (methylation) signatures on DNA molecules|
|Polymerase-chain reaction (PCR)||Amplification of DNA and RNA molecules|
|Real-time PCR||PCR-based quantification of DNA/RNA (commonly used for determining levels of gene expression)|
|RNA-seq/whole transcriptome sequencing||High-throughput sequence analysis of RNA extracted from tissues, to determine amounts of all genes expressed in those tissues|
The above techniques were often developed in the context of academic research and remain used in that setting. However, neuroscientists use these and other techniques while working in a range of different career paths.
Neuroscience and Careers
What Do Neuroscientists do?
Neuroscientists are scientists who are engaged in activities that seek to improve our understanding of the nervous system and its relationship to behaviour and/or disease. Neuroscientists who are principle investigators (and who therefore determine their own research directions) have typically followed a training path consisting of an undergraduate degree in Science (B.Sc.) or Arts (B.A.), usually followed by a Master’s degree, then a Ph.D. in Neuroscience or a related discipline. For those wishing to pursue an academic career, it is common to complete one or more post-doctoral positions, typically at an internationally reputed laboratory. Postdoctoral positions (commonly referred to as postdocs) involve working in the research lab of a principle investigator and leading individual research projects. Post-doctoral fellows also typically take on supervisory responsibilities for other members of the research lab, including graduate students. However, unlike undergraduate or graduate studies, post-doctoral positions do not involve any course work. Instead, the focus is on acquiring techniques and publishing research. An academic, tenure-track appointment at a university is the typical desired outcome for people who have pursued each step of this pathway. However, these jobs have been relatively scarce in the past decade.
In a university environment, neuroscientists may be spread across many different academic units, and departments fully dedicated to the discipline of Neuroscience are relatively rare in North America. For example, neuroscientists may be housed in a department of Psychology, Biology, Pharmacology, Cognitive or Computer Science. From a programmatic perspective, this can be challenging, as students who wish to obtain a degree in Neuroscience often may find that their degree has no ‘home base’, and instead consists of courses that may have a focus on neuroscience, but are housed in multiple, related units. Further compounding this issue is that neuroscience is not commonly taught in high school but may sometimes be included as part of a Biology curriculum. As such, many students graduate from high school not being aware that neuroscience does exist as a discipline of study. That said, neuroscience has been growing over the last few decades, and is becoming more defined as a stand-alone discipline.
Common misconceptions about what Neuroscientists do
There are several common misconceptions regarding what neuroscientists do. For example, it is common to confuse a doctoral (PhD) degree with a medical (MD) degree. However, neuroscientists (who have earned a PhD) are not trained to deliver therapy and they do not treat patients with medicine (as would someone with an MD). Neurologists are specialized medical practitioners who have earned an MD followed by residency training in neurology. Neurologists treat individuals with neurological disorders such as stroke, epilepsy, and Parkinson’s disease. Neurosurgeons have earned a medical degree followed by residency training in neurosurgery; as a surgical profession, neurosurgeons would operate on patients with any damage or trauma to their nervous systems, e.g., tumor excision.
Similarly, there are branches of psychological practice that often are confused with neuroscience: Clinical Neuropsychologists are individuals who have earned a PhD in Clinical Psychology, followed by, or with a specialization in neuropsychology. These individuals have the training to do both research and clinical practice, though they do not have training in medicine. Moreover, they are specialized to assess, diagnose, and treat patients with either congenital or acquired brain injury. Although a fundamental understanding of how the nervous system works is a key component of each of these above-mentioned disciplines (and indeed, it is common for someone interested in pursuing one of these careers to complete a Master’s in Neuroscience prior to completing an MD or Clinical Psychology PhD), it is important to emphasize that research neuroscientists do not treat or provide therapy to patients.
Common careers in Neuroscience
Students graduating with an undergraduate degree in Neuroscience will have developed a range of technical and analytical skills, and the ability to synthesize and communicate research findings in an effective manner. For example, they have developed investigative and research skills in the collection, organization, analysis and interpretation of data, use of appropriate laboratory techniques, application of logical reasoning and critical/analytical thinking, proficiency in computing skills, familiarity with a wide range of scientific/lab equipment, and extensive oral and written communication skills. They are creative thinkers, can work effectively both as individuals and as part of a team, and they have advanced time-management skills. As with most university degree programs, neuroscience is not a vocational program – it does not lead directly into a specific and defined career. Instead, training received as an undergraduate provides students with an excellent foundation for a range of possible careers.
Based on our experience over the last decade, over half of students who graduated with an undergraduate degree in Neuroscience have secured employment in either a scientific research setting, in health care, or are in continuing education. Common research paths for Neuroscience graduates include coordinating clinical research trials or working as research scientists and research technicians in the government, academia or industry. While many graduates are therefore directly employed in a scientific environment, other students chose to pursue graduate degrees in neuroscience or a related discipline (including psychology, biology, biochemistry, pharmacology, ethics).
Graduate degrees can lead towards careers within academia or increase a student’s opportunities of employment in non-academic environments. Health care professions are very popular with Neuroscience graduates. Many students wish to pursue medicine, though being a doctor is just one of many career options in health. Neuroscience graduates have successfully pursued continuing education to train in a variety of professions including psychologists, speech pathologists, occupational therapists, psychologists, medical assistants, nurses, or polysomnographic technicians. While science, healthcare, and future education are the main career paths pursued by neuroscience graduates, almost as many of our graduates have followed alternative routes following graduation, including training as school teachers, working for government funding agencies, regulatory agencies, or the civil service, working in knowledge brokerage, law, or following careers as emergency responders (police, ambulance, firefighters).
Tailoring degrees with minors
In some cases, undergraduate students who have specific career interests are able to tailor their degrees in a manner that facilitate employment in those areas, such as obtaining a degree in Neuroscience with a Minor in Law, or a Minor in Social Work, if these specializations fit their individual career aspirations. In this way, an education in Neuroscience opens the door to many possible careers, without restricting graduates to a limited number of career options. While it impossible to predict the major growth areas in terms of neuroscience career paths, some of the more promising areas for future expansion are described in detail in the following section.
Applications of Neuroscience in Society
Over 1000 neurological and neurodegenerative diseases affect the lives of almost 100 million people in the USA alone (Gooch, Pracht, & Borenstein, 2017), and neuroscience research has led to a diversity of therapeutic approaches to the treatment of diseases including mood disorders, chronic pain, neurodegeneration, stroke, and addiction. Many of these treatments are pharmacological, with widespread use of drugs including antidepressants, anti-anxiety medication, attention deficit hyperactivity disorder medication, etc., though non-pharmacological treatments have also been supported by neuroscientific research, including behavioural/lifestyle modification or external brain stimulation.
Unfortunately, many of the pharmacological interventions have been successful in only a subset of patients, with individuals often having to try several different treatment paths before finding one that is successful. This may be due to many disorders being commonly diagnosed through somewhat imperfect tests, often including self-report measures. A specific disease, defined by a collection of symptoms, may not be a unitary condition but instead a spectrum of related disorders, which collectively have a diversity of different potential origins and associated cellular and molecular signatures. While symptoms may be similar across individuals, the best route for treatment may be very different. Current research attempts to better define subsets of patients for various diseases, to facilitate more efficient targeting of specific treatment to the individual. Understanding the specific cellular and molecular deficits in an individual may be informative as to which molecules would be the best targets for pharmacological treatment.
Public Health: Recreational drugs
Outside of drug development for medical purposes, there is a need for still more neuroscience research on recreational drugs. Use of legal means to control the misuse of recreational drugs (i.e., the ‘war on drugs’) has been of limited success, with a growing interest amongst some nations including Canada towards tolerance and education. We are continually exposed to the use in society of drugs that alter brain activity including some drugs that are common and largely accepted (e.g., nicotine, caffeine, alcohol), drugs prescribed to patients but for which dependency develops (e.g., our current opioid crisis), classical illegal drugs that stimulate our reward systems (e.g., cocaine, heroin) or alter consciousness (e.g., amphetamine, MDMA), drugs used to improve performance (e.g., Ritalin and Adderall for exam performance), or drugs that have been weaponized and used widely (including the date-rape drugs GHB or rohypnol). An important part of any strategy to deal with drug use and misuse is to understand the biological effects (both in the short and long terms) of these various drugs, for which additional neuroscience research and outreach to the community is required.
Public Health: Mental Illness
On a related topic, one of the most compelling (and difficult to measure directly) applications of neuroscience on public health has been the impact of increased understanding of the role of the nervous system in psychiatric and neurological disease. Indeed, over the last 50 years, we have made great strides in our understanding of how key neural circuits and signals are disrupted in several disorders, including (but not limited to) depression, anxiety, schizophrenia, substance use disorders, attention deficit hyperactivity disorder, and dementias such as Alzheimer’s and Parkinson’s Disease, among others. These advances have led to not only the development of pharmacotherapeutics for the treatment of these disorders, but also, crucially, the de-stigmatization of mental health. More specifically, when we educate the public around the role of brain (dys)function underlying psychiatric disorders, it can lead to increased awareness and knowledge, and reduced blame for mental illness (Corrigan & Watson, 2004).
Neuroscience and Technology: Neural interface devices
In addition to pharmacological interventions, neuroscience research is likely to result in growth in the number, efficacy and complexity of neural interface devices. Devices are being developed that both enhance existing sensory inputs (including replacing deficiencies in inputs) or enhance/replace motor outputs. The range of applications is diverse, from the purely medical, to military, to recreational. Neurobionics, a rapidly advancing subfield of neuroscience, explores bionic therapies for sensory and motor impairments.
One example of bionic therapy is for blindness, which affects millions of people worldwide, with a subset of that population suffering from complete retinal degeneration. Among potential treatment options is sensory substitution, wherein an inoperable sensory organ is replaced with an artificial sensor. Most recently, cortical prostheses have taken a leap forward, featuring arrays that are upwards of 192 electrodes in size that are moulded to the occipital lobe of experimental subjects. Miniaturized computers connecting the electrode plates to light-sensing glasses worn by the subject can simulate a small, but promising, degree of vision (Maghbami, Sodagar, Lashay, Riazi-Esfahani, & Riazi-Esfahani, 2014). There are currently several groups of researchers actively engineering and developing visual prosthetics to better the quality of life for those suffering from blindness, Groups such as the Artificial Retina (University of S. California, University of California), The Boston Retinal Implant (Massachusetts Institute of Technology, Massachusetts Eye and Ear Infirmary), C-Sight (Shanghai Jiao-Tong University), Polystim (University of Montréal), Japanese Consortium for an Artificial Retina (Osaka University), and Optoelectronic Retinal Prosthesis (Stanford University) each demonstrate unique and successful efforts to enhance vision for those impaired. Many of these projects combine an external visual processing source (i.e., a camera attached to the frames of glasses), a processor that breaks down visual images into similar bits of information that the brain uses to construct visual images, and a transducer that turns such bits of information into patterns of activation on the microarray of electrodes which then stimulates the visual cortex. Other prostheses exist that are also integrating neural interfaces, such as prosthetic hands that give amputees a functional hand, or cochlear implants that restore function back to the deaf and hearing-impaired.
Neuroscience and the Law
The legal and ethical ramifications of current and future research in neuroscience are likely to be diverse, from which a few examples will be introduced. In criminology, identification of structural and/or functional correlates of criminal behaviour will lead to questions of free will and determinism, and debates about the concept of criminal responsibility. Remaining with the judicial system, neuroscientific research of memory has clear implications for reliability and accuracy of witness testimony. Within pharmacology, there is limited and contentious evidence to support the efficacy of current brain-enhancing drugs (termed “nootropics”) such as Ritalin and Adderall, yet such drugs are widely used in college campuses to improve performance. If the efficacy of these, or other drugs, was clearly demonstrated, it may lead to the need for drug testing analogous to that employed in competitive sport, especially in the context of examinations that are viewed as a component of competitive entry to certain career or funding opportunities.
The last decade has seen dramatic proliferation of wearable biometric technology. Most of our cell phones are quietly collecting information about our daily activity. Some phones can sense when you are looking directly at the screen. Our watches may be constantly collecting data on our heart rate, while we may be inputting data on our sleep patterns, our meditation routines, and/or our patterns of eating and drinking, to name a few. There are important ongoing conversations around the ownership, privacy and security of these data. The coming decades are likely to see growth of biometric inputs to incorporate limited neural data – data that, as with heart rate, we are often unaware of inputting to our devices.
Future Considerations for the Discipline of Neuroscience
The discipline of neuroscience has clearly grown and thrived over the last number of decades. Recent announcements of international, federal and local funding opportunities related to neuroscience and brain health suggest that the study of the nervous system and its application to several branches of society will continue to grow. For example, the Human Brain Project, an ongoing initiative from the European Union, was the winner of one of the largest European scientific funding competitions, with an estimated cost of $1.19 billion euros between 2013-2023. Similarly, the White House BRAIN initiative, announced in 2013, saw an initial investment of over $100 million dollars (US) in the development of neurotechnologies. Despite the dramatic advances in our understanding of the nervous system over the last century, we are just starting to make sense of the enormous complexity that underlies the structure and function of the human brain and how it underlies all thought, behaviour and perception.
Corrigan, P. W., & Watson, A. C. (2004). At Issue: Stop the stigma: Call mental illness a brain disease. Schizophrenia Bulletin, 30(3), 477-479.
Gooch, C. L., Pracht, E., & Borenstein, A R. (2017). The burden of neurological disease in the United States: A summary report and call to action. Annals of Neurology, 81(4), 479-484.
Kandel, E. R., Schwartz, J. H., Jessell, T. M., Siegelbaum, S. A., & Hudspeth, A. J. (Eds.). (2013). Principles of neural science (5th ed.). New York, NY: McGraw Hill
Maghami, M. H., Sodagar, A. M., Lashay, A., Riazi-Esfahani, H., & Riazi-Esfahani, M. (2014). Visual prostheses: The enabling technology to give sight to the blind. Journal of Ophthalmic and Visual Research, 9(4) 494-505.
Squire, L., Berg, D., Bloom, F. E., du Lac, S., Ghosh, A., & Spitzer, N. C. (Eds.). (2012). Fundamental neuroscience (4th ed.). Cambridge, MA: Academic Press.
Latest publications of neurobionics groups
Zhou, D. D., Dorn, J. D., & Greenberg, R.J. (2013). The Argus II Retinal Prosthesis System: An Overview. Proceedings of the IEEE International Conference on Multimedia and Expo Workshops (ICMEW), USA, 1, 1-6. doi: 10.1109/ICMEW.2013.6618428
Kelly, S., Shire, D. B., Chen, J., Gingerich, M. D., Cogan, S. F., Drohan, W. A., … Rizzo, J. F. (2013) Developments on the Boston 256-Channel Retinal Implant. Proceedings of the IEEE International Conference on Multimedia and Expo Workshops (ICMEW), USA, 1, 1-6. doi: 10.1109/ICMEW.2013.6618445
Lu, Y., Yan, Y., Chai, X., Ren, Q., Chen, Y., & Li, L. (2013). Electrical stimulation with a penetrating optic nerve electrode array elicits visuotopic cortical responses in cats. Journal of Neural Engineering, 10(3), 036022. https://doi.org/10.1088/1741-2560/10/3/036022
Mathieson, K., Loudin, J., Goetz, G., Huie, P., Wang, L., Kamins, T. I., … Palanker, D. (2012). Photovoltaic retinal prosthesis with high pixel density. Nature Photonics, 6(6), 391–397. https://doi.org/10.1038/nphoton.2012.104
Ohta, J., Noda, T., Sasagawa, K., Tokuda, T., Terasawa, Y., Kanda, H., & Fujikado, T. (2013). A CMOS microchip-based retinal prosthetic device for large numbers of stimulation in wide area. IEEE International Symposium on Circuits and Systems (ISCAS), 642–645. https://doi.org/10.1109/ISCAS.2013.6571924
Mohammadi, H. M., Ghafar‐Zadeh, E., & Sawan, M. (2012). An Image Processing Approach for Blind Mobility Facilitated Through Visual Intracortical Stimulation. Artificial Organs, 36(7), 616–628. https://doi.org/10.1111/j.1525-1594.2011.01421.x
Please reference this chapter as:
Stead, J., Wiseman, A., & Hellemans, K. (2019). Neuroscience and careers. In M. E. Norris (Ed.), The Canadian Handbook for Careers in Psychological Science. Kingston, ON: eCampus Ontario. Licensed under CC BY NC 4.0. Retrieved from https://ecampusontario.pressbooks.pub/psychologycareers/chapter/neuroscience-and-careers