Brain Facts Notes

Brain Facts: A Primer on the Brain and Nervous System

Preface

• Over the past two decades, knowledge about the brain and nervous system has increased exponentially.

• Neuroscientists use tools and technologies to understand how the brain: controls and responds to the body, drives behavior, and forms the foundation for the mind.

• Research is essential for therapies for over 1,000 nervous system disorders, affecting >1 billion people worldwide.

• Scientists must communicate with the public, informing students, teachers, parents, medical caregivers, and policymakers about neuroscience.

• Students need clear, easy-to-use information on this topic.

• The Society for Neuroscience (SfN) presents the seventh edition of Brain Facts: A Primer on the Brain and Nervous System, substantially revised with updated research and a new section on animal research.

• Information reorganized into six sections for easier understanding.

• The launch of BrainFacts.org, a public information initiative, coincides with the seventh edition of Brain Facts.

• BrainFacts.org is a resource for authoritative public information about brain research progress and promise.

• It will be updated with the latest neuroscience information while the Brain Facts book will continue to be a vital teaching and outreach tool.

Contents

• Part 1: Introduction to the Brain

  • Chapter 1: Brain Basics

  • Chapter 2: The Developing Brain

• Part 2: Sensing, Thinking, and Behaving

  • Chapter 3: Senses and Perception

  • Chapter 4: Learning, Memory, and Language

  • Chapter 5: Movement

  • Chapter 6: Sleep

• Part 3: Across the Lifespan

  • Chapter 7: Stress

  • Chapter 8: Aging

• Part 4: Brain Research

  • Chapter 9: Kinds of Research

• Part 5: Diseases and Disorders

  • Chapter 10: Childhood Disorders

  • Chapter 11: Addiction

  • Chapter 12: Degenerative Disorders

  • Chapter 13: Psychiatric Disorders

  • Chapter 14: Injury and Illness

• Part 6: Treating Brain Disorders

  • Chapter 15: Potential Therapies

  • Chapter 16: Neuroethics

Introduction

• The human brain is a complex structure with the capacity to create networks surpassing any social network and store more information than a supercomputer.

• It enables achievements like walking on the moon, genome mapping and art masterpieces.

• The brain controls heart rate, sexual activity, emotion, learning, and memory, immune response, and influences response to medical treatments and shapes thoughts, hopes, dreams, and imaginations.

• Neuroscientists study the brain and nervous system, discovering that each person has ~100 billion neurons.

• Communication between neurons forms the basis of brain function.

• Research aims to understand human behavior, prevent/cure brain disorders, and advance understanding of the world.

• Over 1,000 brain and nervous system disorders result in more hospitalizations than heart disease or cancer.

• Neurological illnesses affect >50 million Americans annually, costing >$500 billion to treat.

• Mental disorders strike 44 million adults a year at a cost of $148 billion.

• Delaying Alzheimer’s onset by 5 years could save $50 billion in health care costs.

Recent Findings in Neuroscience

• Genetics: Disease genes identified for epilepsies, Alzheimer’s, Huntington’s, Parkinson’s, and ALS - providing insight into mechanisms and suggesting treatments.

• Mapping the human genome has aided identification of genes contributing to or causing neurological disease.

• Animal genomes mapping aids search for genes regulating complex behaviors.

• Gene-Environment Interactions: Major diseases have a genetic basis influenced by the environment.

• Identical twins (same DNA) have increased risk of same disease, but if one twin gets a disease, the probability the other will be affected is between 30%-60%, showing environmental factors matter.

• Environmental influences: exposure to toxic substances, diet, physical activity, and stressful life events.

• Brain Plasticity: The brain can modify neural connections to adapt.

  • Scientists uncover the molecular basis of plasticity, for learning/memory and reversing declines.

  • Adult brains continually generate new nerve cells (neurogenesis).

  • The hippocampus, active in neurogenesis, is heavily involved in learning and memory.

• New Therapies: Insight into molecular neuropharmacology (how drugs affect neurons) gives a new understanding of addiction.

  • Advances have led to new treatments for depression and obsessive-compulsive disorder.

  • Animal venoms can be adapted as pharmacological treatments.

  • Tetrodotoxin (TTX) from puffer fish poison halts electrical signaling in nerve cells; in targeted doses, TTX can shut down nerve cells involved in sending constant signals of chronic pain.

• Imaging: PET, fMRI, and optical imaging show brain systems underlying attention, memory, and emotions.

  • These techniques point to dynamic changes in schizophrenia and other disorders.

• Cell Death: Discoveries of how and why neurons die, along with stem cells discoveries, have clinical applications.

  • Improved chances of reversing effects of injury in brain and spinal cord.

  • Effective treatments for stroke and spinal cord injury based on these advances are under study.

• Brain Development: New understanding gives better insight into childhood disorders like cerebral palsy.

  • Along with stem cell discoveries, pointing to strategies for helping the brain or spinal cord regain lost functions.

Chapter 1: Brain Basics

Anatomy of the Brain and Nervous System

*The brain is the body’s control center, managing everything we do.
*The brain is organized into parts with specific jobs.
*Working with the nervous system, the brain sends and receives messages.

Mapping the Brain

• The cerebrum, the largest part of the human brain, controls voluntary behavior.

  • Thinking, perceiving, planning, and understanding language.

  • It is divided into two hemispheres.

• Bridging the hemispheres is the corpus callosum, used for communication.

• The cerebral cortex is the outermost layer of the cerebrum; its gray color gives it the name "gray matter."

  • It is folded into grooves to increase its surface area.

• The cerebral cortex can be divided into zones:

  • Frontal lobe: Motor movement, higher cognitive skills (problem solving, thinking, planning, and organizing), personality, and emotional makeup.

  • Parietal lobe: Sensory processes, attention, and language; damage to the right side causes difficulty navigating spaces while damage to the left side impairs language understanding.

  • Occipital lobe: Visual information processing, including shape and color recognition.

  • Temporal lobe: Auditory information processing, integration of information from other senses, short-term memory (hippocampal formation), and learned emotional responses (amygdala).

• Other Forebrain parts Include:

  • Basal Ganglia: Coordinate muscle movements and reward useful behaviors.

  • Thalamus: Passes sensory information to the cerebral cortex.

  • Hypothalamus: Control center for appetites, defensive and reproductive behaviors, and sleep-wakefulness.

• The midbrain has pairs of small hills called colliculi.

  • Critical for visual and auditory reflexes and relaying this information to the thalamus.

  • The midbrain regulates activity in the central nervous system and is important for reward mechanisms and mood.

• The Hindbrain includes the pons and the medulla oblongata.

  • Control respiration, heart rhythms, and blood glucose levels.

  • The cerebellum controls movement and cognitive processes requiring timing; plays a role in Pavlovian learning.

• The spinal cord extends from the brain through the vertebral column.

  • Receives sensory information from below the head, uses it for reflexes (e.g. pain), and relays it to the brain and cerebral cortex.

  • Generates nerve impulses in nerves that control muscles and viscera through reflexes and voluntary commands from the cerebrum.

The Parts of the Nervous System

• The forebrain, midbrain, hindbrain, and spinal cord form the central nervous system (CNS).

  • The brain is protected by the skull.

  • The spinal cord (17 inches long) is protected by the vertebral column.

• The peripheral nervous system (PNS) consists of nerves and ganglia (concentrations of gray matter).

• The nervous system is a biological computing device of gray matter interconnected by white matter.

• The brain sends messages through the spinal cord to peripheral nerves, controlling muscles and internal organs.

• The somatic nervous system connects the CNS with the outside world (e.g. neck and arms).

• The autonomic nervous system connects the CNS with internal organs.

  • The sympathetic nervous system mobilizes energy during stress.

  • The parasympathetic nervous system conserves energy during relaxed states, including sleep.

• Messages are carried throughout the nervous system by neurons

The Neuron

• Neurons communicate with each other in unique ways.

• The neuron is the basic working unit of the brain that transmits information to other nerve cells, muscle, or gland cells.

• The mammalian brain contains between 100 million and 100 billion neurons.

  • Each neuron has a cell body, dendrites, and an axon.

    • The cell body contains the nucleus and cytoplasm.

    • The axon extends from the cell body.

    • Dendrites receive messages from other neurons.

• Synapses are contact points for neuron communication.

  • Dendrites are covered with synapses from other neurons.

• Neurons transmit electrical impulses along axons, which vary in length.

• Myelin sheath (made by glia) accelerates electrical signal transmission.

  • Oligodendrocytes make the myelin sheath in the brain.

  • Schwann cells make the myelin sheath in the peripheral nervous system.

• The brain contains at least 10x more glia than neurons

  • Glia transport nutrients to neurons, clean up brain debris, digest dead neurons, and hold neurons in place.

  • Research uncovers new roles for glia in brain function.

• Nerve impulses involve the opening and closing of ion channels that are selectively permeable, water-filled molecular tunnels that pass through the cell membrane and allow ions (electrically charged atoms) or small molecules to enter or leave the cell.

• Ion flow creates electrical current and voltage changes across neuron’s cell membrane.

• A neuron’s ability to generate impulse depends on the charge difference between inside and outside of cell.

• An action potential (reversal in membrane electrical potential from negative to positive) passes along the axon’s membrane at hundreds of miles per hour.

• A neuron may fire impulses multiple times per second.

• Voltage changes trigger neurotransmitter release at nerve terminals, which diffuse across the synapse and bind to receptors on the surface of the target cell (neuron, muscle, or gland cell).

• Receptors act as on-and-off switches for the next cell.

  • Each receptor has a distinctly shaped region that recognizes a particular chemical messenger.

  • The neurotransmitter fits like a key into a lock, altering the target cell’s membrane potential and triggers a response (action potential, muscle contraction, enzyme stimulation, neurotransmitter release inhibition).

• Increased neurotransmitter understanding and drug effects on chemicals is a large neuroscience research area.

• Scientists hope it will help then become more knowledgeable about circuits responsible for disorders such as Alzheimer’s and Parkinson’s diseases.

• The nervous system has two great divisions: the central nervous system (CNS), which consists of the brain and the spinal cord, and the peripheral nervous system (PNS), which consists of nerves and small concentrations of gray matter called ganglia. The brain sends messages via the spinal cord to the body’s peripheral nerves, which control the muscles and internal organs.

• Sorting out the various chemical circuits is vital to understanding the broad spectrum of the brain’s functions, including how the brain stores memories, why sex is such a powerful motivation, and what makes up the biological basis of mental illness.

Neurotransmitters and Neuromodulators

• Acetylcholine (ACh): The first neurotransmitter identified by scientists.

  • Released by neurons connected to voluntary muscles, causing them to contract and by neurons that control the heartbeat.

  • It is a transmitter in many brain regions and is synthesized in axon terminals.

  • When an action potential arrives at nerve terminal, electrically charged calcium ions rush in, and ACh is released into the synapse, where it attaches to ACh receptors on the target cells.

  • On voluntary muscles, this action opens sodium channels and causes muscles to contract.

  • ACh is broken down by the enzyme acetylcholinesterase and resynthesized in the nerve terminal.

  • Antibodies that block one type of ACh receptor cause myasthenia gravis, characterized by fatigue and muscle weakness.

  • It may be critical for normal attention, memory, and sleep.

  • ACh-releasing neurons die in Alzheimer’s patients, so restoring this neurotransmitter is a goal of current research.

  • Drugs that inhibit acetylcholinesterase and increase ACh in the brain are presently the main drugs used to treat Alzheimer’s disease.

• Amino Acids: Widely distributed throughout the body and brain that serve as the building blocks of proteins.

  • Glycine and gamma-aminobutyric acid (GABA) inhibit the firing of neurons.

    • GABA activity is increased by benzodiazepines (e.g., valium) and by anticonvulsant drugs.

    • In Huntington’s disease, GABA-producing neurons degenerate, causing uncontrollable movements.

  • Glutamate and aspartate act as excitatory signals, activating N-methyl-d-aspartate (NMDA) receptors, which, in developing animals, have been implicated in activities ranging from learning and memory to development and specification of nerve contacts.

    • Stimulation of NMDA receptors may promote beneficial changes in the brain, whereas overstimulation can cause nerve cell damage or cell death.

    • Developing drugs that block or stimulate activity at NMDA receptors holds promise for improving brain function and treating neurological and psychiatric disorders.

• Catecholamines: Include dopamine and norepinephrine.

  • They are present in the brain and peripheral nervous system.

  • Dopamine is present in three principal circuits in the brain.

    • The dopamine circuit that regulates movement has been directly linked to disease; dopamine deficits in the brain causes symptoms such as muscle tremors, rigidity, and difficulty in moving for people with Parkinson’s disease.

      • Administration of levodopa, a substance from which dopamine is synthesized, is an effective treatment for Parkinson’s, allowing patients to walk and perform skilled movements more successfully.

    • Another dopamine circuit is thought to be important for cognition and emotion; abnormalities in this system have been implicated in schizophrenia.

      • Drugs that block certain dopamine receptors in the brain are helpful in diminishing psychotic symptoms, so learning more about dopamine is important to understanding mental illness.

    • In a third circuit, dopamine regulates the endocrine system, it directs the hypothalamus to manufacture hormones and hold them in the pituitary gland for release into the bloodstream or to trigger the release of hormones held within cells in the pituitary.

  • Deficiencies in norepinephrine occur in Alzheimer’s, Parkinson’s, and Korsakoff’s syndrome; these conditions lead to memory loss and a decline in cognitive functioning, thus norepinephrine may play a role in both learning and memory.

    • Norepinephrine is secreted by the sympathetic nervous system throughout the body to regulate heart rate and blood pressure.

    • Acute stress increases release of norepinephrine from sympathetic nerves and adrenal medulla.

• Serotonin: Present in the brain and other tissues, particularly blood platelets and the lining of the digestive tract that is an important factor in sleep quality, mood, depression, and anxiety.

  • It controls different switches affecting emotional states, scientists believe these switches can be manipulated by analogs, chemicals with molecular structures similar to that of serotonin.

  • Drugs that alter serotonin’s action, such as fluoxetine, relieve symptoms of depression and obsessive-compulsive disorder.

• Peptides: Short chains of amino acids that are linked together, synthesized in the cell body, and greatly outnumber the classical transmitters discussed earlier in this chapter.

  • In 1973, scientists discovered receptors for opiates on neurons in several regions of the brain, suggesting that the brain must make substances very similar to opium, and therefore scientists made their first discovery of an opiate peptide produced by the brain and named it enkephalin or literally, “in the head.”

  • The precise role of naturally occurring opioid peptides is unclear; simple hypothesis is that they are released by brain neurons to minimize pain and enhance adaptive behavior.

  • Some sensory nerves contain peptide called substance P, which causes sensation of burning pain.

    • Active component of chili peppers, capsaicin, causes the release of substance P, something people should be aware of before eating them.

• Trophic Factors: Researchers have discovered several small proteins in the brain that act as trophic factors; these factors are are necessary for the development, function, and survival of specific groups of neurons.

  • These small proteins are made in brain cells, released locally in the brain, and bind to receptors expressed by specific neurons.

  • Researchers also have identified genes that code for receptors and are involved in the signaling mechanisms of trophic factors.

  • These findings should also prove useful for the design of new therapies for brain disorders of development and for degenerative diseases, including Alzheimer’s disease and Parkinson’s disease.

• Hormones: The endocrine system is a major communication system of the body.

  • The nervous system uses neurotransmitters, but the endocrine system uses hormones.

  • The pancreas, kidneys, heart, adrenal glands, gonads, thyroid, parathyroid, thymus, and even fat are all sources of hormones.

  • The endocrine system works in large part by acting on neurons in the brain, which controls the pituitary gland, and to other endocrine glands, so this system is very important for activation and control of basic behavioral activities, such as sex; emotion; responses to stress; and eating, drinking, and the regulation of body functions, including growth, reproduction, energy use, and metabolism.

  • The brain is very malleable and capable of responding to environmental signals, the brain contains receptors for thyroid hormones (those produced by the thyroid) and the six classes of steroid hormones, which are synthesized from cholesterol– androgens, estrogens, progestins, glucocorticoids, mineralocorticoids, and vitamin D, and are found in selected populations of neurons in the brain and relevant organs in the body.

  • Thyroid and steroid hormones bind to receptor proteins that in turn bind to DNA and regulate the action of genes that can result in long-lasting changes in cellular structure and function.

  • The brain has receptors for many hormones; for example, the metabolic hormones insulin, insulin-like growth factor, ghrelin, and leptin, and hormones are also important agents of protection and adaptation, but stress and stress hormones, such as the glucocorticoid cortisol, can also alter brain function, including the brain’s capacity to learn.

  • Reproduction in females is a regular, cyclic process driven by circulating hormones and involving a feedback loop; the neurons in the hypothalamus produce gonadotropin-releasing hormone (GnRH), a peptide that acts on cells in the pituitary.

  • In males and females, it causes two hormones — the follicle-stimulating hormone (FSH) and the luteinizing hormone (LH) to be released into the bloodstream, and act on receptors on cells in the testes, where they promote spermatogenesis and release the male hormone testosterone, an androgen, into the bloodstream.

  • Increased levels of sex hormones also induce changes in cell structure and chemistry, leading to an increased capacity to engage in sexual behavior.

  • Sexual differentiation of the brain is caused by sex hormones acting in fetal and early postnatal life, although recent evidence suggests genes on either the X or Y chromosome may also contribute to this process.

  • Scientists have found statistically and biologically significant differences between the brains of men and women that are similar to sex differences found in experimental animals., and affect many brain regions and functions, ranging from mechanisms for perceiving pain and dealing with stress to strategies for solving cognitive problems.

• Gases and Other Unusual Neurotransmitters: Scientists have identified a new class of neurotransmitters that are gases.

  • These molecules — nitric oxide and carbon monoxide — are not stored in any structure.

  • They are made by enzymes as they are needed and released from neurons by diffusion, and gases simply diffuse into adjacent neurons and act upon chemical targets, which may be enzymes.

  • Nitric oxide has already been shown to play several important roles as it governs erection in the penis and also governs the relaxation that contributes to the normal movements of digestion in the nerves of the intestine.

  • Nitric oxide controls the intracellular messenger molecule cyclic GMP.

  • In conditions of excess glutamate release, as occurs in stroke, neuronal damage following the stroke may be attributable in part to nitric oxide.

• Lipid Messengers: In addition to gases, which act rapidly, the brain also derives signals from lipids.

  • Prostaglandins are a class of compounds made from lipids by an enzyme called cyclooxygenase, and these very small and short-lived molecules have powerful effects, including the induction of a fever and the generation of pain in response to inflammation.

    • Aspirin reduces a fever and lowers pain by inhibiting the cyclooxygenase enzyme.

  • The brain’s own marijuana, referred to as endocannabinoids, because they are in essence cannabis made by the brain, control the release of neurotransmitters, usually by inhibiting them, and can also affect the immune system and other cellular parameters still being discovered.

    • They increase in the brain under stressful conditions.

• Second Messengers: Substances that trigger such communication are called second messengers.

  • Second messengers convey the chemical message of a neurotransmitter (the first messenger) from the cell membrane to the cell’s internal biochemical machinery.

  • Second messenger effects may endure for a few milliseconds to as long as many minutes, and an example of the initial step in the activation of a second messenger system involves adenosine triphosphate (ATP), the chemical source of energy in cells.

  • Second messengers also are thought to play a role in the manufacture and release of neurotransmitters and in intracellular movements and carbohydrate metabolism in the cerebrum.

  • Second messengers also are involved in growth and development processes and may lead to long-term alterations in cellular functioning and, ultimately, to changes in behavior.

Chapter 2: The Developing Brain

The Journey of Nerve Cells

• The intricate communication among the brain's billions of interacting cells gives the human brain its amazing abilities.

• Although connectivity patterns are shaped by genes and environment, much of brain cell development occurs prenatally.

• Developmental neurobiology is largely focused on cell specialization, travel, and connection into adaptive networks.

• Brain development studies have become increasingly relevant for medical treatment.

• Diseases once thought to be disorders of adult function, such as schizophrenia, are now being considered in developmental terms:

  • Such disorders may occur because pathways and connections to the brain did not form correctly early in life.

• Brain development knowledge is essential for understanding its ability to reorganize in response to external influences or injury.

• Different learning abilities and vulnerability to brain disorders emerge during infancy and childhood.

• Neuroscientists are beginning to discover general principles that underlie developmental processes, many of which overlap in time.
  *All of this includes neural induction, cell proliferation, migration, differentiation, axon growth, synapse formation, and cell death.

Induction

*In early embryonic development, three layers emerge:
* Endoderm.
* Ectoderm.
* Mesoderm.

• These cells undergo interactions to grow into an organ, bone, muscle, skin, or nerve tissue.

• Signaling molecules released by the mesoderm turn on certain genes and turn off others.
  *When some ectoderm cells become nerve tissue, it is called neural induction, and this tissue is refined into neurons/ glia and subclasses of cell types.

• Remaining cells of the ectoderm, not receiving signaling molecules, become skin.

• Proximity of cells to signaling molecules determines their fate because the concentration weakens further from its source.

• A signaling molecule, called sonic hedgehog, is secreted from mesodermal tissue beneath the developing spinal cord, and the adjacent nerve cells are converted into a specialized class of glia.

Migration

• Once neural induction occurs, migration is the next step for the new neurons.

• It starts three to four weeks after conception when the ectoderm thickens and builds up its middle.

• This builds and plate with ridges that fold in toward each other.

• These ridges then fuse to form a hollow neural tube.

• The top of the neural tube thickens into three bulbs that form the hindbrain, the midbrain, and the forebrain.

• In week seven the first signs of the hemisphere appear.
  *Neurons move from the inner surface of the zone to the outer surface, where they begin to accumulate and then migrate to their final destination.

• The most common guidance mechanism (90% in humans) comes from glia, which project radially from an intermediate zone to the cortex.

• Inhibitory interneurons migrate tangentially across the brain.
  *Migration is a delicate process, and factors such as alcohol, cocaine, or radiation can prevent proper migration, resulting in misplacement of cells, which may lead to mental retardation or epilepsy.

Making Connections

• Once the neurons reach their final location, they must make the proper connections to emerge a particular function.
  *Activity such as listening to a voice and responding to a toy lead to more connections between neurons.

• Neurons are interconnected via

  • The growth of dendrites, extensions of the cell body that receive signals from other neurons.

  • The growth of axons, extensions from the neuron that can carry signals to other neurons.

• Growth cones, enlargements on the axons tip, explore the environment to seek their destination as guidance molecules are released by cells to contact axon's end

• When particular ligands are bound with a receptor, the growth cone moves forward or stops.

  • These signaling molecules include proteins with names such as netrin, semaphorin, and ephrin.

• After axons reach their targets, they form connections with another cell at synapses, where the electrical signal of the sending axon is transmitted by neurotransmitters to the receiving dendrites of another neuron.

• For processing to occur properly, the connections must be highly specific.
  * Additional molecules can help with target recognition.
  *Dendrites are actively involved in the process of recruiting proteins and synapse differentiation once contact is made.

Myelination

*Myelination: Glia extensions wrap axons to insulate like wire, increasing transmission speed by factor of 100.

• Nodes of Ranvier are myelin gaps with fast signal jump, known as saltatory conduction.

Paring Back

*Neural networks are pared back after growth to refine system to efficient adult processes.

• Neurons lose life-sustaining trophy factors signals and thus undergo apoptosis by activated cells’ own death programs.
  *Brain cells also form excess connections and need pruning away by signals.

Critical Periods

*Genes and environment converge to form circuits underlying behavior during early development.

• Critical periods (postnatal life) are key for sensory, movement, and emotional input for proper neural development.
  *After a critical period, connections diminish in number and are less subject to change, the brain becomes set.

• Injury or deprivation dramatically reshapes underlying circuit development at sensitive stages, making correction harder in later life.
  *Enriched environments or stimulation bolster brain development by increasing more branches and connections on their neurons than in isolated animals.

Plasticity

*Plasticity means that the brain can modify itself and adapt to different challenges of the environment.
*Can be categorized as experience-expectant or experience –dependent.

• Experience-expectant plasticity
  * refers to the need to integrate environmental stimuli into the normal patterns of development, such as languages in childhood.

• Experience-dependent plasticity

If we figure out how to restrict adult plasticity -- either pharmacologically or rewiring — it may be possible to correct damage or issues during critical periods.