Structure and Functions of the Nervous and Endocrine Systems

Structure and functions of the nervous and endocrine systems and ways in which these systems coordinate the organ system Nervous System: Structure and Function (BIO) • Major functions o High level control and integration of body systems ▪ Frontal lobe: carries out executive functions like planning, impulse inhibition ▪ Cerebellum: integrates, processes sensory, motor, vestibular input ▪ Cerebrum: processes and interprets sensory information. Impose higher level meaning on this information based on previous experience. Top-down influence o Adaptive capability to external influences o Sensory input ▪ Sensory = afferent ▪ Nerve impulses conveyed to the CNS o Motor output ▪ Motor = efferent ▪ Nerve impulses from CNS to effector organs o Integrative and cognitive abilities • Organization of vertebrate nervous system o Categories of nervous systems ▪ CNS = Central Nervous System = Brain and spinal cord • Brain • Spinal cord ▪ PNS = Peripheral Nervous System = Everything else, deal with sensory and motor functions • Sensory = Afferent = Nerves carrying signal toward CNS • Motor = Efferent = Nerves carry signal toward effector organs o Somatic Nervous System = Voluntary = Controls skeletal muscles o Autonomic Nervous System = Involuntary = Effects visceral organs ▪ Sympathetic division = fight or flight response ▪ Parasympathetic division = Rest o Divisions of brain (in ascending order of complexity) ▪ “Lower brain,” brainstem, cerebellum, diencephalon (thalamus, hypothalamus) • Brainstem: controls basic involuntary functions, includes medulla, pons, midbrain o Medulla: regulates cardiovascular and respiratory systems o Pons: coordinates communication between motor cortex and cerebellum o Midbrain: relay station for auditory, visual signals • Cerebellum: see above • Thalamus: processes all sensory information before it reaches a higher cortical level • Hypothalamus: maintains homeostasis. Works together with pituitary gland to exercise feedback control of hormone release o Ex. release of hormone → greater enzyme activity → signals to brain don’t need more hormone → hypothalamus tells pituitary to chill ▪ “Higher brain,” Cerebrum • Frontal lobe: see above • Motor, somatosensory cortex: topographic map, homunculus • Limbic system: made up of hippocampus, amygdala. Concerned with memory and emotion o Lateralization of cortical functions ▪ Language: production and comprehension localized in left hemisphere ▪ • • • Emotion: left hemisphere more involved with positive emotions, right with negative emotions Sensor and effector neurons o Sensor = senses, carries sensory signals from body to CNS o Effector = causes an effect = carries motor signals from CNS to body Sympathetic and parasympathetic nervous system: antagonistic control o Sympathetic = prepares body for activity = fight or flight response ▪ Increase heart rate, blood pressure ▪ More blood flow to muscles, less to digestive system ▪ Pupil dilation ▪ Break down glycogen to release glucose into blood o Parasympathetic = prepares body to rest = rest and digest response ▪ Decrease heart rate, blood pressure ▪ Less blood to muscles, more to digestive system ▪ Pupil constriction ▪ Synthesizes glycogen for storage from glucose o Both innervate the same organs, have opposing influences on the same organs, their signals compete with each other = antagonistic control o Location of sympathetic and para cell bodies relative to the things they effect ▪ Sympathetic: far from effectors (because need distance to generate strong, coordinated signal needed for flight or flight) ▪ Parasympathetic: close to effectors, give more uncoordinated signals ▪ Effector: organ or muscle that responds to neural innervation o Type of NT’s used by each ▪ Parasympathetic: acetylcholine ▪ Sympathetic: epinephrine or norepinephrine Reflexes o Feedback loop, reflex arc ▪ Feedback loop = positive feedback (reinforce initial event), negative feedback (counteracts initial event), or reflex arc (usually a type of negative feedback) • Positive feedback = uterine contraction lead to oxytocin release, which causes more uterine contractions • Positive feedback = blood clotting platelets activated at wound site attract more platelet activation and clumping • Negative feedback = drop in blood pressure causes ADH release, which increases it. Conversely increase in blood pressure causes a drop in ADH • Reflex arc = withdrawal from a painful stimulus = negative feedback • Reflex arc = knee jerk = tapping the knee tendon causes sudden stretching of the muscle, which lead to contraction of that muscle that creates the knee jerk = negative feedback ▪ Reflex arc = receptor → sensory neuron → integration center → motor neuron → effector • Receptor = site of stimulus • Sensory neuron = carries impulse from receptor to integration center • Integration center = connects sensory to motor neuron via synapse inside the CNS o Monosynaptic = no interneuron, direct synapse of sensory to motor o Polysynaptic = interneuron(s) present • Motor neuron = carries impulse toward effector • Effector = site of response to the stimulus ▪ Examples of reflexes: knee-jerk, withdrawal from pain ▪ Effects on flexor and extensor muscles • • During the knee-jerk, in addition to contracting the extensor, the reflex relaxes the flexor • Golgi tendon reflex: sudden contraction of the quads (extensor), causes a negative feedback that relaxes the quads and contracts the hamstrings (flexor) o Role of spinal cord and supraspinal circuits ▪ Spinal cord provides the synapse (or synapses if it’s polysynaptic) for the reflex arc ▪ Even though the reflex arc bypasses the brain, the brain is still aware of it happening ▪ Reflex sends signals to CNS via spinal cord, CNS perceives stimulus and prepares more complex response ▪ Supraspinal circuits: descend from CNS to inhibit reflexes, fine tune them so they proceed smoothly Integration with endocrine system: feedback control o Feedback control in hypothalamus. Communicates with pituitary o Pituitary sends out hormones which have effect → signal of hormone effects ready by hypothalamus → hypothalamus tells pituitary to chill Nerve Cell (BIO) • Cell body: site of nucleus, organelles o Contains nucleus and organelles just like any other cell o Has well-developed RER and golgi (makes lots of proteins) • Dendrites: branched extensions of cell body o Receptive region of the nerve = gets input o Branching helps increase surface area for reception • Axon: structure and function o Axon = conducting region of the nerve o Axon terminals = secretory regions of nerve o Other names for axon terminal = synaptic knob = bouton • Myelin sheath, Schwann cells, insulation of axon o Myelin sheath = covers the axon intermittently, with gaps called nodes of Ranvier o Purpose of myelin sheath is to speed up conduction by insulating the nerve in intervals. This intermittent insulation causes action potential to jump from one node of Ranvier to the next o Schwann cells = makes myelin sheath in the peripheral nervous system by wrapping around the axon o Oligodendrocytes = the central nervous system analogue of Schwann cells, makes myelin sheath around CNS axons o Insulation of axon = achieved by myelin sheath. Insulation occurs in intervals, which causes action potential to jump from one node of Ranvier to the next o Myelin sheath is a good insulator because it is fatty and does not contain any channels • Nodes of Ranvier: propagation of nerve impulse along axon o Action potential jumps from one node of Ranvier to the next o This jumping of action potential speeds up conduction in the axon • Synapse: site of impulse propagation between cells o Synapse = conduction from one cell to another o Axodendritic synapse = axon terminal of one neuron (presynaptic) → dendrite of another neuron (postsynaptic) o Axosomatic synapse = axon terminal of one neuron (presynaptic) → cell body of another neuron (postsynaptic) o Axoaxonic synapse (rare) = axon terminal of one neuron (presynaptic) → axon hillock of another (postsynaptic) • Synaptic activity: transmitter molecules o Transmitter molecules = neurotransmitters • • o Action potential → release of neurotransmitters by presynaptic axon terminal → picked up by receptor of postsynaptic neuron o Release of neurotransmitter = exocytosis of vesicles containing neurotransmitters. Triggered by calcium influx when action potential reaches axon terminal. o Neurotransmitter reception = diffusion of neurotransmitter across the synaptic cleft, binds to receptor, opens up ion channels that causes a change in membrane potential of the postsynaptic neuron (graded potential). If this graded potential is large enough, it will trigger a full-fledged, all-or-nothing action potential in the postsynaptic neuron o Neurotransmitters are quickly eliminated (destroyed by enzymes, reuptake by presynaptic terminal, or diffuse away) so that they don’t persistently stimulate the postsynaptic neuron o Neurotransmitter molecules: ▪ Acetylcholine (ACh) ▪ Norepinephrine (NE) ▪ Dopamine ▪ Serotonin ▪ Histamine ▪ ATP o Synaptic knobs ▪ Another name for axon terminal ▪ Contains vesicles of neurotransmitters waiting to be exocytosed ▪ Action potential reaching the synaptic knob causes an influx of calcium, which signals the vesicles to fuse with cell membrane (exocytosis) to release the neurotransmitters into the synaptic cleft o Fatigue ▪ Continuous synaptic activity → depletion of neurotransmitters → fatigue o Propagation between cells without resistance loss ▪ Action potential is all-or-nothing ▪ As long as neurotransmitters cause the postsynaptic cell to reach a certain threshold potential, the action potential induced is just as large as the presynaptic action potential ▪ In summary, propagation between cells involves no resistance loss because the postsynaptic action potential is just as large as the presynaptic potential - all action potentials are all-or-nothing o Firing of synapse causes change in postsynaptic membrane potential ▪ EPSP: excitatory postsynaptic potential, adds up to cause action potential ▪ IPSP: inhibitory postsynaptic potential, adds up to discourage action potential o Acetylcholine vs epinephrine in parasympathetic, sympathetic nervous systems ▪ All preganglionic neurons in autonomic and postganglionic neurons in parasympathetic nervous system use acetylcholine ▪ Postganglionic neurons in sympathetic nervous system use epinephrine Resting potential: electrochemical gradient o Na+-K+ pump = 3 Na+ out, 2 K+ in = net negative to the inside, net positive to the outside o K+ leakage = the resting cell membrane has channels that allow K+ to leak out, but don’t allow Na+ to leak in = net negative to the inside, net positive to the outside o Resting potential is -70 mV because the cell is more negative on the inside, and more positive on the outside o Electrochemical gradient = combination of electrical and chemical gradient = both electrical potential and ion concentration gradient across membrane Action potential o Stages of an action potential: ▪ 1. Resting: cell at rest, sodium-potassium pump maintaining resting potential (-70 mV). Lots of sodium outside, lots of potassium inside. Ion channels closed so the established ion gradient won’t leak ▪ • • 2. Depolarization: sodium channels open, positive sodium rushes inside, membrane potential shoots up to +30 mV. Lots of sodium inside, lots of potassium inside. ▪ 3. Repolarization: potassium channels open, sodium channels close, positive potassium rushes outside, membrane potential drops back down. Lots of sodium inside, lots of potassium outside (opposite of resting state) ▪ 4. Hyperpolarization: potassium channels don’t close fast enough, so membrane potential drops below resting potential for a bit ▪ 5. Refractory period: sodium-potassium pump works to re-establish the original resting state (more potassium inside, sodium outside). Until this is done, the neuron can’t generate another action potential. • Absolute refractory period = from depolarization to the cell having re-established the original resting state • Relative refractory period = after hyperpolarization till resting state re-established o Threshold, all-or-none ▪ When a stimulus (graded potential) depolarizes above a threshold value, an action potential will occur ▪ Action potentials are all-or-none, meaning that if it occurs, all action potential have the same magnitude ▪ One graded potential just barely makes the threshold value, another overshoots it a lot, but both will cause same action potential o Sodium/potassium pump ▪ 3 sodium out ▪ 2 potassium in ▪ Net positive out ▪ Causes membrane to be more negative on the inside, hence negative membrane potential Excitatory and inhibitory nerve fibers: summation, frequency of firing o Excitatory = stimulates an action potential to occur o Excitatory synapse = receptor binding causes postsynaptic potential to be more positive (depolarization) = if it gets above threshold, action potential results o Inhibitory = inhibits an action potential from occurring o Inhibitory synapse = receptor binding causes postsynaptic potential to be more negative (hyperpolarization) = makes it more difficult to reach threshold o Summation = two or more nerves firing at the same time ▪ Two subthreshold excitatory nerves firing at the same time can sum to reach the threshold ▪ A threshold excitatory nerve and an inhibitory nerve firing at the same time, and the resultant signal won’t reach the threshold o Frequency = firing, then quickly firing again ▪ If the first fire is subthreshold, fire again before the previous depolarization dies, and the new depolarization will be even higher than the first time Glial cells, neuroglia o Qualities of glia ▪ Capable of cell division, multiply to fill empty space in CNS after trauma ▪ Do not convey electrical signals ▪ Often responsible for brain cancer o 6 types of glial cells ▪ 1) Microglia: macrophages, break down debris and potentially harmful microbes ▪ 2) Ependymal cells: help circulate cerebrospinal fluid ▪ 3) Satellite cells: support ganglia (neuronal bodies in PNS) ▪ 4) Astrocytes: star shaped cells in CNS, give physical support to neurons and maintain mineral and nutrient balance in interstitial space ▪ 5) Oligodendrocytes: myelinate multiple axons at one time in CNS, arms extend outwards which myelinate ▪ 6) Schwann cells: myelinate single axons in PNS o White vs grey matter: white = myelinated fiber tracts, grey = bundles of neuron bodies Electrochemistry (GC) • Concentration cell: direction of electron flow, Nernst equation o Half reactions ▪ Oxidation half reaction describes the species that loses electrons (increases in charge) ▪ Reduction half reaction describes the species that gains electrons (decreases in charge) o Reduction potential = potential of the reduction half reaction o Oxidation potential = potential of the oxidation half reaction = reverse the sign of the reduction potential o Cell potential = Reduction potential + Oxidation potential o Direction of electron flow ▪ Electrons always flow from the Anode to the Cathode. Mnemonic: A to C in alphabetical order. ▪ Oxidation (at the anode) produces electrons (and cations) and shoots out electrons toward the cathode. The cathode receives those electrons and uses them for reduction. ▪ Naturally, the species with the highest oxidation potential (lowest reduction potential) will be the anode, and the species with the highest reduction potential will be the cathode ▪ Electrons flow in wires and electrodes, while ions flow in the electrolyte solution, thus creating a completed circuit o Nernst equation ▪ ▪ At 298 K, and in base 10 log form, the equation is • E = E˚ + .06/n log(Q) Used to find potential difference in a cell in nonstandard conditions Biosignaling (BC) • Gated ion channels: let ions from one side of membrane to another o Voltage gated ▪ Na and K voltage gated channels: involved in action potential. Speed at which they open are different ▪ Ca2+ voltage gated channels: located at presynaptic side of synaptic cleft. Action potential causes channels to open, Ca2+ to flow into cell. This causes efflux of NT vesicles o Ligand gated ▪ Transmembrane proteins activated by binding of a specific ligand ▪ “Lock and key” model ▪ When ligand binds to allosteric site, channel opens up • Receptor enzymes: bind neurotransmitters or hormones and trigger processes in cell o Neurotransmitter binding to receptor makes postsynaptic side more permeable to ions. This completes the transfer of the neural impulse o Neurotransmitters released back into cleft after binding to receptor ▪ Need ways to get rid of neurotransmitters in cleft • Destroy using an enzyme in the cleft • Reabsorb into presynaptic side • • Diffuse out of cleft G protein-coupled receptors o Example of secondary messenger system o Binding of neurotransmitter to this receptor causes release of an attached G-protein’s alpha subunit o Alpha subunit release in postsynaptic neuron has variety of effects: ▪ 1) activates separate specific ion channels ▪ 2) activate a second messenger (ex. cAMP) ▪ 3) activate intracellular enzymes ▪ 4) activate transcription Lipids (BC, OC) • Description, structure o Description; varying structures but all have low solubility in water and high solubility in nonpolar organic solvents ▪ Major classes: fatty acids, triacylglycerols, phospholipids, glycolipids, sphingolipids, steroids, terpenes, waxes o Steroids ▪ Four-ringed structures ▪ Maintain membrane stability, fluidity. Precursor for steroid hormones • Cholesterol and membrane fluidity o Moderate to high temps: Cholesterol makes membranes more rigid by attracting adjacent phospholipid tails o Low temps: Cholesterol makes membrane more fluid by filling in gaps between phospholipid tails o Terpenes and terpenoids ▪ Part of pigments in the body ▪ ex. Vitamin A (important for vision) Endocrine System: Hormones and Their Sources (BIO) • Function of endocrine system: specific chemical control at cell, tissue, and organ level o Endocrine system = make hormones = specific control of all target cells of that hormone • Definitions of endocrine gland, hormone o Endocrine glands secrete hormones into surrounding tissue fluids o Endocrine vs exocrine, autocrine, paracrine ▪ Endocrine: hormone, no duct, acts long distances ▪ Exocrine: non-hormone secretions into ducts ▪ Autocrine: local chemicals, act short distances on themselves ▪ Paracrine: local chemicals, act short distances on other cells o Hormone = chemicals that regulate metabolism and function of cells • Major endocrine glands: names, locations, products o Hypothalamus, Posterior Pituitary (hydrophilic, peptide) ▪ Releasing hormones/factors stimulates pituitary to release its hormone ▪ GnRH = Gonadotropin Releasing Hormone = stimulates pituitary to release FSH and LH ▪ CRF = Corticotropin Releasing Factor ▪ TRH = Thyroid Releasing Hormone ▪ Dopamine = inhibits prolactin release ▪ GHRH = Growth Hormone Releasing Hormone ▪ ADH = Antidiuretic Hormone = Vasopressin = water reabsorption in kidney = conserve water, increase blood pressure ▪ Oxytocin = stimulates uterine contractions during labor, also milk secretion during suckling o Anterior Pituitary (hydrophilic, peptide) ▪ FSH = Follicle Stimulating Hormone = Stimulate ovary follicles to mature, testis to produce sperm ▪ LH = Luteinizing Hormone = LH surge triggers ovulation, stimulates testis to produce testosterone ▪ ACTH = AdrenoCorticoTropic Hormone = Stimulates adrenal cortex to release glucocorticoids and mineralocorticoids ▪ TSH = Thyroid Stimulation Hormone = Stimulate thyroid to release thyroid hormones ▪ PRL = Prolactin = Stimulates breast to product milk ▪ E = Endorphins ▪ GH = Growth Hormone = Stimulates growth of muscle, bone, burns fat o Pineal: makes melatonin, which makes you sleepy at night o Thyroid (hydrophilic AND hydrophobic, tyrosine AND peptides) ▪ Thyroid hormones: increase metabolism, requires iodine ▪ Calcitonin: turns blood Ca2+ into bone. Lowers blood Ca2+ • o Parathyroid (hydrophilic, peptide) ▪ Makes Parathyroid Hormone (PTH), which increases blood Ca2+ by bone resorption, dietary calcium absorption, and calcium reabsorption in kidneys ▪ Gut: increases calcium uptake in gut ▪ Kidney: increases phosphate excretion, forming insoluble calcium phosphate when phosphate reacts with calcium o Thymus: stimulates T cells to develop o Adrenal cortex (hydrophobic, steroids) ▪ Mineralocorticoids = aldosterone = increase Na+ and water retention, raises blood pressure ▪ Glucocorticoids = cortisol = longer-term stress response compared to medulla hormones, responds more to chronic instead of acute stress ▪ Androgens = testosterone o Adrenal medulla (hydrophilic, tyrosine) ▪ Supplement nervous system activity by secreting neurotransmitters into the blood (provides slower, more generalized sympathetic nervous system response) ▪ Epinephrine and norepinephrine = fight or flight response • Constrict blood vessels of internal organs/skin, dilate blood vessels on skeletal muscle o Pancreas (hydrophilic, peptide) ▪ Glucagon = increases blood sugar (break down glycogen, stimulate gluconeogenesis) ▪ Insulin = lower blood sugar (stimulates glucose uptake by cells) o Testes and ovaries ▪ Hormones stimulate reproductive development functions ▪ Testosterone (testes): facilitates male puberty and spermatogenesis ▪ Progesterone and estrogen (ovaries): facilitates female puberty, menstruation, and pregnancy o Placenta ▪ Secretes peptide hormone to prepare uterus to support pregnancy ▪ HCG signals for ovaries to continue making progesterone and estrogen → suppresses menstruation, allowing for buildup of uterine wall Major types of hormones o 3 major types of hormones: ▪ Peptide • Water soluble • binds to membrane-bound receptor, triggers second messenger system • Manufactured in RER as prepohormones, cleaved in ER, cleaved and glycosylated in Golgi and then packaged for export ▪ Steroid • Fat soluble • Binds to carrier proteins for transport in bloodstream, diffuses through cell membrane and binds to receptors in cytosol and mitochondria. • Acts on level of transcription so primary mechanism of action is increasing certain protein levels in the effector • Manufactured in SER and mitochondria ▪ Tyrosine • Either water or fat soluble • Thyroid hormones (fat soluble) o Diffuses through membrane to bind to receptors in the nucleus o Strong affinity for binding protein, increases duration of its effects o Primary mechanism of action: increasing transcription of certain genes • • Epinephrine and norepinephrine (water soluble) o Dissolve in blood to bind to receptors on target tissue o Act mainly through secondary messenger cAMP Neuroendocrinology - relation between neurons and hormonal system Endocrine System: Mechanisms of Hormone Action (BIO) • Cellular mechanisms of hormone action o Water soluble hormones ▪ Cannot cross the plasma membrane ▪ Bind to membrane receptors on the outside of cells ▪ Secondary messengers then relay the signal inside the cell o Lipid-soluble hormones ▪ Able to cross the plasma membrane ▪ Directly activate genes o cAMP pathway: ▪ 1) Amino acid hormone binds membrane receptor ▪ 2) G protein activated ▪ 3) Adenylate cyclase activated ▪ 4) cAMP made ▪ 5) Protein kinase cascade o Phospholipid pathway: ▪ 1) Amino acid hormone binds membrane receptor ▪ 2) G protein activated ▪ 3) Phospholipase C activated ▪ 4) Membrane phospholipid split into DAG and IP3 ▪ 5) DAG triggers protein kinase cascade ▪ 6) IP3 release Ca2+ from the ER o Steroid pathway: ▪ 1) Steroid hormone (and thyroid hormone even though it’s amino acid based) goes inside the cell ▪ 2) Hormone binds receptor inside the cell (cytoplasm or nucleus) ▪ 3) Hormone-receptor complex (transcription factor) turns certain genes on inside the nucleus • Transport of hormones: blood supply o Hormones travel long distances via blood and lymph • Specificity of hormones: target tissue o Specificity depends on the target cells having the receptors for the hormone, and non-target cells lacking receptors for the hormone o Cells can either upregulate or downregulate the receptors they express • Integration with nervous system: feedback control o The nervous system can modulate and override normal control of hormones based on the status of the body. For example, the body’s blood “normal” glucose level is set higher when you’re under stress o Hormones can modulate the nervous system. For example, low estrogen levels during menses give you a bad mood o Normal control of hormones ▪ Humoral: glands directly respond to chemical levels in the blood (parathyroid response to low blood calcium) ▪ Neural: glands release hormones when stimulated by nerves (fight or flight response) ▪ Hormonal: glands release hormones when stimulated by other hormones • Regulation by second messengers o Second messengers are molecules that relay signals received at receptors on the cell surface such as the arrival of protein hormones, growth factors, etc. - to target molecules in the cytosol and/or nucleus o The amplify the strength of the signal o 3 major classes of second messengers: ▪ Cyclic nucleotides (e.g. cAMP and cGMP) • Binding of hormone to its receptor activates a G protein which activates adenylyl cyclase • The resulting rise in cAMP turns on appropriate response in cell by either (or both): o Changing molecular activities in cytosol using Protein Kinase A (PKA) - a cAMP dependent protein kinase that phosphorylates target proteins o Turning on a new pattern of gene transcription ▪ Inositol triphosphate (IP3) and diacylglycerol (DAG) • Peptide and protein hormones activate the intracellular enzyme phospholipase C - hydrolyzes phospholipids • DAG remain in inner membrane and recruits Protein Kinase C (PKC) - a calcium dependent kinase that phosphorylates many other proteins that bring about changes in the cell • Inositol-1,4,5-triphosphate (IP3) diffuses through cytosol and binds to receptors on ER causing release of Ca2+ into cytosol ▪ Calcium ions (Ca2+) • Most widely used intracellular messengers • Can trigger many events such as muscle contraction, exocytosis, activation of T cells and B cells, adhesion to extracellular matrix, apoptosis, and biochemical changes mediated by Protein Kinase C