Ch 11: Nervous system

General steps:

1. Sensory input (Sensory nerve fibers/afferent division)

2. Integration (CNS)

3. Motor output (motor nerve fibers/efferent division)

Basic architecture:

• Central Nervous System = brain and spinal cord (integrative/control)

• Peripheral Nervous System = cranial and spinal nerves (communication btwn CNS and body)

• Sensory division = somatic and visceral sensory fibers (impulses from receptors to CNS)

• Motor division = conducts impulses from CNS to effectors (muscles/glands)

  • Somatic nervous system = voluntary; from CNS to muscles

  • Autonomic nervous system = visceral/involuntary; from CNS to cardiac, smooth, glands

    • Sympathetic division = mobilizes body during activity

    • Parasympathetic division = conserves energy; promotes housekeeping during rest

Neuroglia: supportive cells in nervous system

• astrocytes - support, organize, clean (neurotransmitters), feed; form blood/brain barrier; most abundant

• microglial cells - immune roles (ordinary WBC cannot cross blood/brain barriers)

• ependymal cells - line CSF spaces; produce CSF (choroid plexus of ventricles)

• oligodendrocytes - form myelin sheath around CNS axons (interacts with multiple)

• satellite cells - surround PNS cell bodies (similar to astrocytes)

• Schwann cells - form myelin sheath around PNS axons (single portion of axon)

Neurons:

• Highly elongated (axon/dendrite structure); high metabolic rate (aerobic); highly differentiated structure (cannot divide); long lived (lifetimes)

• Dendrites - receptive/input regions, convey messages toward body

• cell body - metabolic center, clusters in CNS=nuclei, clusters in PNS=ganglia

• axon hillock - initiates AP in response to EPSP depolarization to threshold. “trigger zone”

• Schwann cells/myelin sheath - insulates axon; lipid (plasma membrane); accelerates AP

• node of Ranvier - gaps in myelin to allow for saltatory conduction

• axon - propagates AP to terminus

• axon terminal - secretory region, releases neurotransmitters to communicate

  • AP terminated; triggers Ca⁺² influx, exocytosis of NT by synaptotagmin and SNAP/SNARE complex

    
    

• afferent (sensory) neuron - transmit sensory info towards CNS (unipolar - one branched process [T], sensory of PNS)

• efferent (motor) neuron - carry impulses away from CNS (multipolar - many dendrites and one axon, common in CNS; body in CNS)

• interneurons - btwn motor/sensory neurons; through CNS; 99% of neurons; multipolar

  • bipolar - one dendrite, one axon; rare, typically in special senses

Membrane potentials

• Resting potential - established by Na⁺/K⁺ ATPase (3 Na out, 2 K in; active ion pump); -70mV;

  • K⁺ has higher permeability (leaks out of cell and leaves behind anions; leak channels); Na⁺ leaks into cell MUCH slower, maintains conc. gradient)

  • Resting potential depends on the permeabilities of ions (closest to equilibrium of K⁺)

• Graded potential - incoming (local) signals with varying strength (not all or nothing); must add up before it initiates an AP; current decreases with distance and varies with strength of stimulus

  • depolarization - decrease in membrane potential (EPSP; closer to AP threshold; -55mV; Na⁺ channels [voltage gated ion channels])

    • inactivation gate of channel prevents continuous activation; one way propagation

  • hyperpolarization - increase in membrane potential (IPSP; Cl^- or VG K⁺ channels)

  • receptor potential - graded potential at sensory neuron due to physical or chemical change

  • postsynaptic potential - graded potential produced by ligand-gated ion channels (LGICR) in postsynaptic cell (NT, NM, hormone)

• Action potential - long distance signal of axon (always same strength)

  • initiation/threshold - depolarization at hillock opens VG-Na⁺ channels (-55mV)

  • depolarization - Na⁺ influx changes polarization to +30mV

  • repolarization - K⁺ channels open as a result of potential change, influx into cell and decreases potential to baseline

    • absolute refractory period - when channels are open/resetting (inhibitory gate) another AP cannot occur; also why it propagates unidirectionally

    • AP don’t last forever due to diffusion, leak channels, Na/K pump

  • hyperpolarization - continued flow of K⁺ decreases to -90mV

  • recovery - ions slowly restore back to resting potential through leaky channels and ATPase

    • relative refractory period - AP requires greater stimulation to reach threshold, but it can still occur

• Conduction velocity - size and degree of myelination

  • Size - larger diameter = less resistance = faster conduction

  • Myelination - much faster when myelinated

• Strength of signal - based on frequency and number of nerve cells engaged

• Saltatory conduction - AP '“jumps” from nodes of Ranvier (insulated wave propagation, ion flow to maintain AP only at nodes)

Neuron Interfaces

• Synapses

  • axodendritic - btwn axon ending of presynaptic cell and postsynaptic dendrite (typically chemical)

  • axosomatic - direct interface btwn presynaptic axon and postsynaptic soma (body); stronger effect due to proximity to axon hillock

  • axoaxonic - (rare) connection btwn axon terminus and axon (important in neuromodulation [alteration of strength of synapse by external forces])

  • electrical - gap junctions; physical portal btwn two cells for direct ion transfer/conduction of AP (rare - smooth/cardiac but NOT muscle)

  • chemical - rely on NT to bridge gap btwn cells and carry message

    • AP induces VG-channel to allow Ca⁺² into the terminus; vesicular fusion triggered by Ca⁺² binding to synaptotagmin, conformation change, SNARE complex proteins form vesicles for exocytosis

    • Termination: 1) diffusion of ligand out of synapse (often reabsorbed by astrocytes); 2) reuptake by presynaptic cell for recycling/storage; 3) breakdown by enzymes in synaptic cleft

    • synaptic delay - chemical (diffusion limited)/physical (membrane/protein rearrangement) limitations of NT (0.3-5.0 ms); slower than electrical wave; synapse = rate limiting step (gap junctions are the fastest!)

• Signaling summation

  • Temporal - increased frequency (helps reach threshold); one pre and one postsynaptic

  • Spatial - helps reach threshold; many pre and one postsynaptic

  • EPSP - excitatory (depolarizing) stimulus (Na⁺); must be summed before AP produced

  • IPSP - inhibitory (K⁺ channels or Cl^-); if present, EPSP must overcome to activate AP (integration)

• Synaptic potentiation - repeated/continuous use enhances ability to excite (larger EPSP); accumulation of Ca⁺² in terminus or more complicated

• Presynaptic inhibition - hyperpolarize axons (axoaxonic), inhibit NT release, smaller EPSP

• Long-term potentiation (LTP) - sensitizing synaptic firing patterns in hippocampus; neural pathway is easier to trigger by some stimulus

  • postsynaptic receptor upregulation (DISCUSSED LATER); Ca⁺² ionotropic sensitization; increased NT synthesis

Neurotransmitters

• NT - chemicals that carry signals btwn neurons (or effector tissue)

  • chemical ID is not sufficient to determine action; actions are based on receptors (same NT can have different effect based on different receptors); different signal transduction pathways

  • metabotropic - activates signal transduction pathway (G-protein, secondary messengers); can alter many cell functions (enzyme activity, gene expression, ion channels)

  • ionotropic - activates LGICR to directly alter membrane potential in postsynaptic neuron (EPSP or IPSP)

• NM (neuromodulator) - chemical signal released that affects strength of transmission (not directly EPSP or IPSP); TUNE not GENERATE signal

• acetylcholine

  • nicotinic cholinergic receptor (NAchR); ionotropic, EPSP; skeletal muscle stimulation (PNS); nicotine is agonist, increases sympathetic activation

  • muscarinic cholinergic receptor (MAchR); metabotropic, M2-G_i inhibitory, M1/M3 excitatory; PaANS, inhibits smooth muscle and pacemaker, stimulates digestion; muscarine is agonist, atropine is antagonist, used to control HR

• norepinephrine/epinephrine

  • alpha adrenergic receptors; metabotropic, a1 excitatory, a2 inhibitory; a1 stimulate smoother muscle constriction, a2 are autoreceptor negative feedback; a1 agonists for vasoconstrictors, a2 for vasodilation

  • beta adrenergic receptors; metabotropic, mostly excitatory (B1, B3), B2 inhibitory; B1, excitatory, increase HR and cardiac contractile force (blockers lower HR and BP); B2, smooth muscle relaxation (agonists used to reverse airway constriction); B3, lipolysis, thermogenesis

• dopamine (dopaminergic receptor); metabotropic, neuromodulatory; limbic system (emotion), desire/reward, motivation, satisfaction, motor relays in midbrain (Parkinson’s); monoamine oxidase inhibitor (MAOI) inhibits degradation, increasing dopamine levels, treats depression

• serotonin, 5-HT (serotonergic receptor); metabotropic, neuromodulatory; sleep, wakefulness, emotional state, perception, modulates CNS, stomach activity; serotonin reuptake inhibitors (SSRI) increase serotonin in synapses, reduce depression, LSD stimulates receptors

• glutamate (glutamatergic receptors); ionotropic, EPSP; stimulatory of CNS; NMDA antagonists are anesthetics, dissociative euphoriants, alcohol is iGluR antagonist

• GABA (gabaergic receptors); inonotropic, IPSP; inhibitory of CNS; benzodiazepine agonists reduce anxiety and/or muscle tone (xanax), alcohol is agonist and slows CNS

Ch 14: Autonomic Nervous System

Autonomic Nervous System - unconscious actions/changes in homeostatic set points (metabolism, reflexes, heart rate, blood pressure, respiration, digestion, etc.); Sympathetic and Parasympathetic; visceral

• SyANS: moves body towards action

  • effector origin: thoracic and lumbar spinal cord

  • short preganglionic (ganglia along spinal cord); long post ganglionic

  • ACh (nicotinic), epinephrine/norepinephrine

  • extensive preganglionic branching

  • adrenal and sweat glands involved

  • elevated HR, pupil dilation, vaso-constriction/dilation, increased ventilation, inhibit glands and digestion, stimulates epinephrine production, increased metabolic rate

    • vascular system is under sympathetic tone at rest

    • Uniquely SyANS: thermoregulation (blood vessel dilation/sweat glands); release of renin from kidneys (blood pressure); metabolic effects

• PaANS: moves body towards rest (maintain homeostasis)

  • effector origin: cranial nerves, sacral spinal cord

  • long preganglionic fibers (ganglia near/within organs)

  • ACh, (nicotinic and muscarinic)

  • limited preganglionic branching

  • slows HR, stimulates digestion, promotes peeing, restricts ventilation, sexual arousal

    • under tone: cardiac activity (pacemaker of heart is around 100bpm, PaANS is inhibitory), digestive and urinary activity, immunity

  • Vagus nerve - primary visceral sensory and PaANS effector pathway for all organs in thorax and abdomen (90% of fibers); PaANS is focused on digestive, heart, lungs

• Dual innervation: both SyANS and PaANS control; allows for fine tuning (rapid and precise changes); easier to “come down” from SyANS to enter PaANS state

  • Mostly antagonistic, “push-pull” control

  • Cooperative action: sexual excitation and urination

• Visceral vs Somatic NS

  • involuntary (Somatic NS: voluntary)

  • sensory - general sensations/action for organs, run with autonomic fibers (SNS: general sensations from integument and superficial regions of body; run with motor neurons; muscles)

  • stimulates OR inhibits, modulatory (SNS: stimulation only)

  • dual-fiber pathways, require synapses at autonomic ganglia (SNS: single-fiber pathway, cell body in spinal cord and axon termini at target)

  • NT: ACh preganglionic, acetylcholine (muscarinic) or adrenergic post ganglionic, epinephrine (SNS: ACh, glutamate and GABA in CNS)

Brain regions:

• spinal cord - lateral horns (effector bodies), medial dorsal horn (visceral reflexes)

• brain stem - cranial nerves and where they originate (manage ANS, network spanning these regions); ventrolateral medulla (HR and blood vessel diameter), medullary region (gastrointestinal), midbrain (pupil diameter and focus)

• hypothalamus - overall control; anterior (CRH, PaANS); posterior (ACTH, SyANS)

• limbic system and cortex - emotional state; fear response w amygdala; remembered stress w hippocampus

  • Conscious thought does not control ANS, but emotion and memory (so relaxation) can affect ANS tone; good for managing chronic stress from SyANS

Chapter 15: Endocrine system

Exocrine - “secreted outside”; chemical signals that leave internal space of body (enter lumen or exit skin); released by ducts; non-hormonal

Endocrine - “secreted inside”; chemical signals for communication; released by glands into blood stream (reach most cells)

• hormone - long distance (global) signaling between tissues through the blood (or lymph)

• paracrine - “secreted along side”; short distance (released into ISF to near-by tissues; act locally); can be the same chemical as hormone

• autocrine - “secreted by self”; short distance (target the same cell that released it); negative feedback

Hormones:

• water soluble: fast-acting, short-lived; GPCR or RTK signaling

  • amines - nitrogenated compounds; acetylcholine (made from phospholipid, NOT a lipid), biogenic amines (amino acid derivatives: epi/norepi, dopamine, thyroid hormone, serotonin, melatonin

    • catecholamines - derivatives of tyrosine (dopamine, norepinephrine, epinephrine, thyroid hormones)

    • indolamines - derivatives of tryptophan (serotonin, melatonin)

  • peptides - small protein fragments; hypothalamic and pituitary hormones

    • fragments of polypeptide gene products; produced similarly to proteins, but are clipped (by proteases) rather than folded; one gene can produce many signaling peptides

  • proteins - posttranslationally modified before active; insulin, prolactin

  • eicosanoids - most paracrines, highly modified fatty acid; BP, pain, swelling

• lipid soluble: long-acting, long-lived, enter cell and act deep within (change transcription)

  • steroids - cholesterol derivative; adrenal and gonadal

    • need to be transported by carrier proteins, diffuse directly through cell membranes, activate internal receptors

    • glucocorticoids - glucose metabolism, stress

    • mineralocorticoids - sodium reabsorption

    • gonadocorticoids - sex hormones

  • thyroid hormone - modified amine, acts like steroid

Stimulation

• Humoral: direct change in blood ion/glucose concentration

• Neural: response to neural stimulation (neuron or neurotransmitter); adrenaline in response to ACh

• Hormonal: response to another hormone; aldosterone in response to ACTH

  • tropic = hormones that stimulate the production/release of other hormones

    • hypophysiotropins = released by hypothalamus into hypophyseal portal to stimulate anterior pituitary (different from neurological stimulation to posterior pituitary)

Response

• cell response is based on receptor and the signal transduction at those receptors

• upregulation - persistent low levels = more receptors to increase sensitization

• downregulation - persistent high levels = decreased receptors to tolerate hormone

• permissiveness - hormone cannot exert full effects without other hormone present

• synergy - more than one hormone produces the same effect; amplification

• antagonism - two hormones oppose actions of another

Hypothalamic hormones (stored in posterior lobe)

• GHRH (growth hormone-releasing hormone) - stimulates GH

• GHIR (growth hormone-inhibiting hormone) - inhibits GH, hunger/metabolism

• TRH (thyrotropin-releasing hormone) - stimulates TSH in response to metabolic need

• CRH (corticotropin-releasing hormone) - stimulates ACTH, increased by stress and low BP

• GnRH (gonadotropin-releasing hormone) - stimulates FSH and LH

• DA (PIH) - dopamine, inhibits prolactin

Pituitary hormones

• ACTH; pars distalis; stimulates adrenal cortex, trigger for cortisol; stimulated by CRH

  • Cushing’s disease - hypersecretion of cortisol; characteristic body mass changes, elevated blood glucose, decreased healing, possible sexual development changes, water and mineral balance; typically hypersecretion of ATCH

• ADH; pars nervosa; vasoconstriction, renal water reabsorption; stimulated by low BP, high osmolarity

  • Diabetes insipidus - hypersecretion of ADH; high urinary volume, high thirst/water intake; damage or tumor to hypothalamus or pituitary gland

• endorphins; pars intermedia; natural opioid, pain killer; stimulated by pain/stress

• FSH; pars distalis; sexual development and reproduction, stimulates estrogens; stimulated by GnRH

• GH; pars distalis; tissue growth, activates IGF’s to promote mitosis and tissue growth; stimulated/inhibited by GHRH/GHIH

  • gigantism - hypersecretion of GH during childhood

  • dwarfism - hyposecretion during childhood

• LH; pars distalis; sexual development and reproduction, testosterone and progesterone; stimulated by GnRH

• MSH; pars intermedia; melanocyte activity, melanin production; stimulated by UV exposure

• oxytocin; pars nervosa; contractions, breastfeeding, social attachments and bonding; stimulated by childbirth, breastfeeding, social interaction

• PRL (prolactin); pars distalis; mammary gland development and milk production; stimulated by sex hormones, maybe TRH

• TSH; pars distalis; thyroid gland development and TH production; stimulated by TRH

Pineal gland: endocrine gland in cranium (melatonin)

Thyroid

• Thyroid hormone - tyrosine derivatives; contain iodide and two linked tyrosine AA; secreted by follicular cells as precursors

  • T₃ (triiodothyronine) - high activity form; formed from T₄ at target tissues

  • T₄ (thyroxine) - low activity form

• TSH stimulates thyroid release and stimulation to “restock” follicle lumen; TRH stimulates release; T₃ acts as negative feedback to both TSH and TRH, TRH inhibits TSH

• hormonal ‘throttle’ of metabolic rate, body heat, hunger (inc. sugar uptake, release of fatty acids, mobilizes fuel); permissive to GH; sympathetic activation of B-adrenergic receptors (hyperthyroid can present as high sympathetic activation)

• Goiter - enlarged or protruding thyroid; iodine deficiency = low T₃ = inc TRH and TSH = thyroid growth

• Grave’s disease - hyperthyroid; autoimmune, antibodies target thyroid and stimulate TH release; elevated metabolism, anxiety, insensitivity to cold

• Congenital hypothyroidism - poor development of thyroid in babies (TH needed for neural and physical development)

• parafollicular secretory cells - No known role in humans, calcitonin antagonizes PTH to decrease blood calcium

Parathyroid

• small glands on posterior side of thyroid; produce PTH (parathyroid hormone)

• PTH stimulated by low blood calcium; decreases renal secretion of Ca⁺², increases Vitamin D activation, increases bone reabsorption (osteoclasts)

Adrenal gland (above renal [kidneys])

• Zona glomerulosa - aldosterone (mineralocorticoid); increases Na retention and K excretion by kidney; increases blood volume/pressure; stimulated by RAAS, increase in plasma K, ACTH, inhibited by ANP

• Zona fasciculata - cortisol (glucocorticoids) and some adrenal androgens (in response to ACTH); increases blood sugar/metabolic activity, gluconeogenisis, permissive to adrenaline signaling, chronic stress suppresses growth, immunity, digestion, inflammation; stimulated by ATCH and CRH

  • cortisol supports stress changes with increased fuel, decreased digestion, immune, reproductive and growth actions; stimulated by ATCH

• Zona reticularis - androgens (gonadocorticoids) and some cortisol; stimulated by ATCH; precursors to testosterone and estrogen but also have behavioral roles (sex drive in women); some progesterone made, mostly in ovaries

• Adrenal medulla - produces epinephrine and some norepinephrine

  • adrenaline drives primary stress response (HR, BP, metabolic rate, etc.); stimulated by SyANS

• Addison’s disease - ‘underactive adrenal gland’ or adrenal hyposecretion; ATCH levels rise but insufficient corticosteroids produced; weight loss, low blood sugar, low energy, high K levels, dehydration

Pancreas (both endocrine and exocrine)

• Blood sugar regulators

  • glucagon - stimulated by low blood sugar; alpha cells; stimulates gluconeogenisis (breakdown of fats/proteins to glucose) and glucose release from liver; targets liver and fat

  • insulin - stimulated by high blood sugar; beta cells; stimulated glucose uptake and storage in tissues, fat anabolism, metabolism; synergistic with growth hormone

• digestive regulators

  • somatostatin (SST) - delta cells

  • pancreatic polypeptide (PP) - gamma cells

  • ghrelin - epsilon cells

Other

• leptin, adiponectin, resistin: adipose tissue; “fat” hormones; leptin = increases metabolism, decreases appetite, high fat levels; adiponectin = increased insulin sensitivity, low fat; resistin = increased insulin resistance, high fat

• ANP (atrial natriuretic peptide) - stretch in atrial wall (high BP/volume); inhibits aldosterone release, decreases blood Na and volume

• EPO (erythropoietin), renin: kidneys; EPO = stimulates red blood cell formation, in response to O₂ levels; renin = stimulates aldosterone production, SyANS and urinary flow

• osteocalcin: bone; metabolic regulator, increases insulin production, restricts fat anabolism

• Vitamin D: cholesterol in skin or ingested; absorption of Ca from diet

• IGF1: liver, skeletal muscle, bone; resource/nutrient uptake; stimulated by GH