AA

Chapter 1: Brain Basics

Objectives of Chapter 1

  • I will be able to know the anatomy of the Nervous System
  • I will know the functions and anatomy of the Neuron
  • I will know the functions and different types of neurotransmitters and neuromodulators

Anatomy of the Brain

  • The brain is the body’s control center
  • The brain sends and receives messages, allowing for ongoing communication

Mapping the Brain

  • Cerebrum- the largest part of the brain
    • associated with higher level thinking, including control of voluntary behavior.
    • The cerebrum divided into 2 hemispheres: the left hemisphere & right hemisphere
    • Left and Right hemispheres are connected by a bundle of fibers called the Corpus Callosum
  • Cerebral cortex/gray matter: a sheet of tissue covering outermost layer of cerebrum
  • ⅔ of Cerebral Cortex is folded into grooves to increase surface area for more neurons but not to grow big to break skull
  • 4 main lobes:
    • The Frontal Lobe is responsible for
    • starting & overseeing motor movements,
    • higher cognitive skills (problem solving, thinking, planning, etc.)
    • aspects of personality, and emotional makeup.
    • The Parietal Lobe is responsible for
    • sensory processes (smell, touch, taste)
    • attention
    • language
    • The Occipital Lobe is responsible for
    • processing visual information
    • recognizing shapes & colors
    • The Temporal Lobe is responsible for
    • processing auditory information
    • combining information from other senses.
    • possibly having a role in short-term memory through the hippocampal formation
    • possibly having a role in learned emotional responses through the amygdala
  • The cerebral cortex and all four lobes are in the forebrain.
    • Other forebrain parts include the basal ganglia, hypothalamus, and thalamus
    • Thalamus: passes most sensory information onto cerebral cortex after helping to prioritize that information
    • Hypothalamus: the control center for appetites, defensive + reproductive behaviors, and the circadian rhythm
  • Cerebral nucleus: a cluster of neurons in the CNS (central nervous system)
    • Cerebral nuclei help coordinate muscle movements and reward useful behaviors.
  • The midbrain consists of two pairs of small hills called Colliculi.
    • Colliculus: a small bump, especially one of two pairs in the roof of the midbrain, involved respectively in vision and hearing.
    • The colliculi play a critical role in visual & auditory reflexes and in relaying this type of information to the thalamus.
    • The midbrain also has clusters of neurons that regulate activity in widespread parts of the Central Nervous System(CNS)
    • These are thought to be important for reward mechanisms and mood
  • The hindbrain includes the pons and the medulla oblongata, and the cerebellum
    • Pons and Medulla Oblongata control respiration, heart rhythms, and blood glucose levels
    • Cerebellum has two hemispheres that control the precise timing of movement and cognitive processes
    • also plays an important role in Pavlovian Learning
      • Pavlovian Learning: a learning procedure in which a biologically potent stimulus (e.g. food) is paired with a previously neutral stimulus (e.g. a bell).
  • The spinal cord is the extension of the brain through the vertebral column
    • It receives sensory information from all parts of body below head and uses this information for reflex responses to pain
    • It relays sensory information to the cerebral cortex
    • It creates impulses in nerves that control muscles and viscera through reflex activities and voluntary commands from the cerebrum

The parts of the Nervous System

  • There are two great divisions of the nervous system:
    • Central Nervous System (CNS) - formed by the brain and spinal cord
    • the brain is protected by the skull
    • the spinal cord is protected by the vertebral column
      • it is 17 inches in length
    • Peripheral Nervous System (PNS) - formed by all the other nerves branching off the brain and spinal cord into the body
    • The PNS contains nerves and small concentrations of gray matter called ganglia
  • The nervous system is a vast biological computer formed by gray matter regions interconnected by white matter
  • The brain sends messages via the spinal cord to peripheral nerves that control skeletal muscles and other organs.
  • Somatic Nervous System: made up of neurons connecting CNS to the parts of the body that interact with the outside world
    • This is the part of the nervous system we can voluntarily control
    • Somatic nerves regions and where they control
    • cervical region = neck and arms
    • thoracic region = chest
    • lumbar & sacral region = legs
  • Autonomic Nervous System: made of neurons connecting the CNS with the internal organs, smooth muscle, and cardiac muscle
    • This is the part of the nervous system that we cannot voluntarily control
    • The autonomic nervous system is further divided into two parts:
    • Sympathetic Nervous System: moves around energy and resources in times of stress
      • “fight or flight”
    • Parasympathetic Nervous System: conserves energy during relaxed states and sleep
  • The messages in the nervous system are carried by individual neurons

The Neuron

  • The neuron is the basic working unit of the brain
    • It is a specialized cell designed to transmit information to other neurons, muscle, or gland cells
  • The mammalian brain contains between a 100 million to a 100 billion neurons
    • This number is species dependent
  • Each mammalian neuron has 3 parts
    • Cell body/Soma: the part of the neuron that contains all the cellular machinery it needs to survive (nucleus, mitochondria, etc.)
    • Dendrites: branched extensions of the neuron’s cytoplasm that receive messages from other neurons
    • Axon: mostly linear extension of the neuron’s cytoplasm that sends messages to other neurons
    • The axon gives rise to smaller branches & ends at nerve terminals
    • Neurons transmit electrical impulses along axons to send a message
      • Most axons are covered with a myelin sheath that is made by cells called glia
      • specifically oligodendrocytes in the brain & schwann cells in the PNS
  • Synapses are the contact points where neurons communicate
  • Glia perform many jobs:
    • Transporting nutrients
    • cleaning up debris
    • holding neurons in place
    • digesting dead neurons
    • forming the myelin sheath
  • Nerve impulses involve the opening & closing of ion channels
    • Ion channels: selectively permeable, water-filled molecular tunnels that pass through cell membrane and allow ions or small molecules to enter/leave the cell
  • The flow of ions creates an electrical current that produces tiny voltage changes across the neuron’s cell membrane
    • Membrane potential: the voltage of the cell’s membrane
  • The ability of a neuron to generate an electrical impulse depends on a difference in the charge between the inside & outside of cell
  • When nerve impulse begins, a dramatic reversal in electrical potential occurs on the cell membrane
  • Neuron switches from an internal negative state to an internal positive state
    • This is referred to as an action potential
    • This change then moves along the axon’s membrane
    • Can be at speeds up to several hundreds of mph
    • A neuron may be able to fire multiple impulses every second
  • When these voltage changes reach end of the axon, the release of neurotransmitters occurs
    • Neurotransmitters: the brain’s chemical messengers
    • Neurotransmitters are released at nerve terminals and diffuse across synapses to bind to receptors on the surface of the target cell
      • The target cell is usually another neuron but can be a muscle or gland cell
    • Drugs bring about their effects by acting like neurotransmitters
  • Receptors act as on & off switches for the next cell
    • Each receptor has a distinctly shaped region that recognizes a particular chemical messenger
    • Like a key and lock
    • When a neurotransmitter is in place, this interaction alters the target cell’s membrane potential and triggers a response from the target cell

Neurotransmitters and Neuromodulators

Acetylcholine (ACh)

  • ACh was the first neurotransmitter to be discovered (approximately 80 yrs ago)
  • Main characteristics of ACh
    • It’s released by neurons connected to voluntary/skeletal muscles
    • ACh causes these muscles to contract
    • It’s released by neurons that control heartbeat
    • It’s a neurotransmitter in many regions of the brain
    • It’s synthesized in axon terminals
  • How is ACh released?
    • When action potential comes to the nerve terminal, calcium ions rush into the cell
    • ACh is then released into the synapse where it attaches to ACh receptors on target cells
    • This opens sodium ion channels in the target cell and causes the intended effect to occur
  • Acetylcholinesterase: enzyme that breaks down ACh once it is not needed anymore
    • ACh gets resynthesized again if it is needed
  • Myasthenia Gravis: an autoimmune disease characterized by fatigue and muscle weakness caused by the formation of antibodies that attack ACh receptors on skeletal muscle
  • ACh may be important for normal attention, memory, and sleep
  • ACh-releasing neurons die in Alzheimer’s patients
    • Drugs used to treat Alzheimer’s inhibit acetylcholinesterase & increase ACh in the brain

Amino Acids

  • Amino acids are widely distributed throughout the body and brain
  • They mainly serve as building blocks of proteins but can also serve as neurotransmitters
  • 4 main amino acid neurotransmitters:
    • Glycine
    • Gamma-aminobutyric acid (GABA)
    • Glutamate
    • Aspartate
  • Glycine and gamma-aminobutyric acid (GABA) inhibit the firing of neurons
    • GABA activity is increased by benzodiazepines (e.g., Valium) and by Anticonvulsant Drugs
    • Benzodiazepines are organic chemical substances made of two carbon rings.
    • “Anticonvulsant” means “used to prevent or reduce the severity of epileptic fits or other convulsions.”
  • Huntington’s Disease: a fatal genetic disorder that causes the progressive breakdown of nerve cells in the brain.
    • GABA producing neurons degenerate, which causes uncontrollable movements
    • It deteriorates a person’s physical and mental abilities during their prime working years and has no cure.
  • Glutamate and Aspartate act as excitatory signals.
    • Activate N-methyl-d-aspartate (NMDA) receptors
    • NMDA receptors are involved in activities ranging from learning & memory to development
    • Stimulation of these receptors may be helpful but overstimulation may cause cell death
    • These receptors are involved in cell death due to a stroke or trauma
    • The development of drugs that block or stimulate NMDA receptors hold promise for improving brain function and treating neurological and psychological disorders

Catecholamines

  • This category of neurotransmitters includes dopamine, norepinephrine, and epinephrine
    • This chapter does not really discuss epinephrine
    • They are widely present in the nervous system
  • Dopamine is present in three principal circuits in the brain
    • One dopamine circuit regulates movements
    • Dopamine deficits in the brain cause people w/ Parkinson’s to show symptoms such as muscle tremors, rigidity, difficulty in moving
    • Administration of the drug Levodopa is an effective treatment
      • Allows Parkinson’s patients to walk and more effectively do skilled movements
    • Another dopamine circuit regulates cognition and emotion
    • Abnormalities in this system are related to schizophrenia
    • Drugs that block certain receptors are helpful in diminishing psychotic symptoms
    • Dopamine is important in understanding mental illness
    • Another circuit regulates Endocrine System
    • Dopamine directs hypothalamus to make hormones
    • Makes the hormones go to pituitary gland for release into bloodstream or to activate pituitary cells’ hormones
  • Norepinephrine might play a role in learning and memory
    • It’s also secreted by the Sympathetic Nervous System throughout the body to increase HR and BP
    • Acute stress increases the release of norepinephrine from sympathetic nerves and the adrenal medulla
    • Deficiencies in norepinephrine occur in people with Alzheimer’s, Parkinson’s, and Korsakoff’s Syndrome (disorder associated with alcoholism)
    • All of the above lead to memory loss and decline in cognitive functioning

Serotonin

  • It’s present in the brain, blood, and lining of digestive tract
  • In the brain, serotonin is an important factor in sleep quality, mood, depression, and anxiety
  • Serotonin controls different switches affecting many emotional states
    • Scientists believe that these switches can be manipulated by analogs (chemicals with molecular structures like Serotonin)
  • Drugs that reverse the actions of Serotonin relieve symptoms of depression and OCD

Peptides

  • Peptides: short chains of amino acids synthesized in themcell body
    • These greatly outnumber other transmitters (dopamine, ACh, etc)
    • Peptide neurotransmitters include:
    • enkephalin
    • endorphins
    • Substance P
  • Scientists discovered receptors for opiates on neurons in many regions in 1973
    • This suggests that the brain makes chemicals similar to opium
  • After that, they discovered an opiate peptide produced by brain
    • This peptide resembled the opium derivative morphine
    • The substance was named Enkephalin meaning “in the head”
  • Soon after, many more of these were discovered and were named endorphins
    • Endorphins: a class of opiate-like peptides that were named based on the term “endogenous morphine”
    • The precise role of naturally occurring endorphins is unclear
    • A hypothesis is that they are released by brain neurons to relieve pain and enhance adaptive behavior
  • Substance P: a peptide neurotransmitter causing the sensation of burning pain
    • present in some sensory nerves and tiny unmyelinated fibers
    • Capsaicin: a compound that causes the release of Substance P
    • active component in chillies

Trophic Factors

  • Trophic Factors: substances needed for development, function, and survival of groups of neurons
    • these tend to be small proteins
  • Trophic factors are made in brain cells, released locally in brain, and bind to receptors expressed by specific neurons
  • Genes have been identified that code for the receptors and are involved in signaling mechanisms of trophic factors
    • Theses findings are expected to result in a greater understanding of how trophic factors work for brain
  • Trophic Factors may also prove useful for new therapies of developmental and degenerative brain diseases

Hormones

  • Endocrine system (ES) is a major communication system of the body
  • While the nervous system uses neurotransmitters as chemical signals, the endocrine system uses hormones
  • The endocrine system works by acting on neurons in the brain & controlling the pituitary gland
    • the pituitary gland secretes factors that either increase or decrease hormone production in the glands
    • This is called a feedback loop
      • This involves communication from the brain to the pituitary gland to the endocrine gland and back to the brain
  • The endocrine system is important for
    • activation and control of basic behavioral activities (emotion, responses to stress, drinking)
    • growth
    • reproduction
    • energy use
    • metabolism
  • The way the brain responds to hormones indicates that the brain is very malleable and capable of responding to environmental signals
  • Brain contains receptors for thyroid hormones and 6 classes of steroid hormones
    • Steroid hormones are synthesized from cholesterol
    • The 6 classes of steroid hormones are:
    • androgens
    • estrogens
    • progestins
    • glucocorticoids
    • mineralocorticoids
    • vitamin D.
    • Receptors for thyroid and steroid hormones 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
    • This can result in long-lasting changes in cellular structure and function
  • The brain also has receptors for insulin, ghrelin, and leptin
    • Hormones enter the blood and travel to organs in response to stress and changes in biological clocks
    • Hormones are taken up from blood and act to affect neuronal activity and aspects of neuronal structure
  • In the brain, hormones alter production of gene products that participate in synaptic neurotransmission as well as affect structure of brain cells
    • As a result, the circuitry of brain and its capacity of neurotransmission are changed over a course of hours to days
  • The brain adjusts its performance and control of behavior in response to changing environment
  • Hormones are important agents of protection and adaptation
    • But stress hormones like the glucocorticoid cortisol can also alter brain function
    • This includes brain’s capacity to learn
    • Severe and prolonged stress can impair ability of brain to function normally
    • But the brain is also capable of remarkable recovery
  • Reproduction in females is a good example of regular cyclic process driven by circulating hormones and involving a feedback loop
  • Neurons in the hypothalamus produce gonadotropin-releasing hormone (GnRH)
    • This is a peptide that acts on cells in pituitary
    • In all people this causes the release of two hormones: Follicle-stimulating hormone (FSH) and Luteinizing hormone (LH)
      • Females- causes ovulation and starts releasing Estrogen and Progesterone
      • Males- promotes spermatogenesis, releasing Testosterone (androgen- male sex hormone)
  • The sex hormones include testosterone, estrogen, and progesterone
    • Increased levels of Testosterone/Estrogen signal hypothalamus & pituitary to stop releasing FSH and LH
    • These hormones induce changes in cell structure
    • They increase the capacity to engage in sexual behavior.
    • They have widespread effects on many other functions including attention, motor control, pain, mood, and memory
    • The sexual differentiation of the brain caused by these hormones in fetal and postnatal life
    • The genes on the X and Y chromosomes might contribute to this
  • The male and female brain are biologically different
    • Differences exist in size/shape of brain structures in hypothalamus and arrangement of cortex and hippocampus
    • There are also brain differences in homosexual and heterosexual men

Gaseous and other Neurotransmitters

  • The gaseous neurotransmitters include
    • Nitric oxide
    • carbon monoxide
  • They are not present in any structures (vesicles, etc.)
  • They are made by enzymes as needed and released from neurons by diffusion
  • Gaseous neurotransmitters don’t act at receptor sites
    • Instead, they simply diffuse into adjacent neurons and act upon their chemical targets (may be enzymes)
  • Nitric oxide neurotransmission governs erections
    • Causes the relaxation of intestinal nerves that contributes to normal digestive movements
    • Nitric oxide may also be attributed to excess glutamate release that causes stroke and neuronal damage
  • The major intracellular messenger molecule in the brain is cyclic GMP (Guanosine Monophosphate)

Lipid Messengers

  • Brain also derives signals from lipids
  • Prostaglandins: a class of compounds made from lipids made by an enzyme called cyclooxygenase
  • Prostaglandins have powerful effects:
    • They can induce a fever
    • They can generate pain in response to inflammation
    • Aspirin reduces fever and pain by inhibiting the cyclooxygenase enzyme
  • The second class of membrane-derived messengers is endocannabinoids
    • “Brain’s own marijuana”
    • They control the release of neurotransmitters by inhibiting them
    • They can also affect the immune system
    • They play an important role in the control of behaviors
    • Endocannabinoid levels increase in the brain under stressful conditions

Second Messengers

  • After the action of neurotransmitters, biochemical communication is still possible
  • Second messengers: substances that convey the message of neurotransmitters from the membrane to the internal cell machinery
    • May endure for a few milliseconds to many minutes
    • May also be responsible for long-term changes in the nervous system
  • The initial step of activation is ATP (Adenosine Triphosphate)
    • ATP: the source of energy in all cells
  • When norepinephrine binds to receptors on the surface of a neuron, the activated receptor binds a G protein on the inside of the membrane
  • Activated G protein causes adenylyl cyclase to convert ATP → cAMP (cyclic Adenosine Monophosphate)
    • cAMP: changes the function of ion channels in the membrane and the expression of genes in the nucleus
  • Second messengers are thought to play role in
    • the manufacture and release of neurotransmitters
    • intracellular movements
    • carbohydrate metabolism in the cerebrum
    • growth and development processes
  • Direct effects of second messengers on genetic materials may lead to long-term alterations in cellular functioning and changes in behavior
  • These communication systems in the brain and nervous system develop 3 weeks after the formation of an embryo