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