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