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

\ \