Exam 1 Flashcards
What is the function of neurons?
reception, integration, transmission, and transfer of information
Intracellular vs. Extracellular Ion Concentrations
Sodium: high extracellular concentration
Potassium: high intracellular concentration
Chloride: high extracellular concentration
Calcium: very low intracellular concentration
Three Properties of Ion Channels
1) conduct ions
2) selective for specific ions
3) open and close in response to specific electrical, mechanical, or chemical signal
Non-Gated Ion Channels
always open (leak channels)
Modality-Gated Ion Channels
open and close to a specific stimulus (touch, chemical, photons, etc.)
Ligand-Gated Ion Channels
open following binding of a chemical (ligand) to a receptor on the membrane surface
Voltage-Gated Ion Channels
open in response to changes in the cell membrane potential
Gradients are maintained by…
1) presence of large intracellular anions
2) passive diffusion of ions
3) active transport of sodium and potassium via the Na/K pump
Modulation
the membrane potential can be altered to become either more positive or more negative (gradual and long-lasting change)
Axoplasmic Resistance
smaller axon diameter provides more resistance
Membrane Resistance
leakage of ions results in decreased strength of charge
Lidocaine
blocks voltage-gated sodium channels
Tetrodotoxin (TTX)
blocks voltage-gated sodium channels
Lethal Injection (KCl)
eliminated the concentration gradient by flooding the extracellular space with potassium
Dehydration/Overhydration
alters resting membrane potential and affects action potential generation
Guillain-Barre Syndrome
autoimmune response against myelin. Slowing of nerve conduction and response.
Charcot-Marie-Tooth Disease
progressive neural muscular atrophy with weakness in arms and feet; loss of reflexes, loss of sensation, and muscular atrophy
Multiple Sclerosis
disease attacks the myelin sheaths in the brain, spinal cord, and optic n.
ALS
destruction of alpha motor neurons that give rise to the corticospinal tract and motor neurons in the spinal cord and brainstem
Myasthenia Gravis
autoimmune disease that affects the NMJ. Pts display fatigue and exhaustion. Antibodies develop against the ACh receptor.
Where are synapses located?
- neurons in the brain
- brain and spinal cord neurons (via spinal cord tracts)
- neurons in the spinal cord
- spinal cord neurons and anterior horn cells (motor)
- peripheral nerves and muscles
- autonomic fibers and target organs
Types of Synapses
- axo-somatic: often inhibitory
- axo-dendritic: often excitatory
- axo-axonic: often modulatory
Neuromotransmitters
a chemical induces a response in post-synaptic membrane via ligand-gated receptors, then the chemical is acting as a neurotransmitter: can be excitatory or inhibitory
Neuromodulators
act to alter neuronal functions by acting at a distance away from the synaptic cleft. They are released into the extracellular fluid and can modulate many neurons simultaneously (ex: Substance P).
Presynaptic Facilitation
slightly depolarizes axon, fires longer when action potential arrives; more neurotransmitter is released
Presynaptic Inhibition
slightly hyperpolarizes neuron, action potential duration decreased; less neurotransmitter is released
Acetylcholine
neurotransmitter at NMJ (excitatory) and in ANS; in CNS it is primarily a neuromodulator
Neurotransmitters: Amino Acids
- glutamate
- aspartate
- gamma aminobutyric acid (GABA)
- glycine
Neurotransmitters: Amines
- dopamine
- histamine
- serotonin
- norepinephrine
Neurotransmitters: Peptides
- substance P
- endorphines
- enkephalins
- calcitonin gene-related peptide (CGRP)
- galanin
Nicotinic Receptors
responsible for binding ACh; brief opening cation channels
Muscarinic
responsible for binding ACh; slow-acting G-protein mediated effects
Glutamate
major excitatory NT in the CNS
Ionotropic Receptors
responsible for binding glutamate
- NMDA: voltage and ligand-gated cation channel (calcium, sodium, and potassium)
- AMPA, KA: ion channels, fast depolarization of post synaptic neuron
Metabotropic Receptors
G-protein mediated
GABA, Glycine
major inhibitory NT in the CNS
GABAa
ligand-gated anion channel; chloride
GABAb
g-protein coupled receptor linked to anion channel
Norepinephrine Receptors: alpha-1
G-protein coupled receptor that causes increased IP3 and calcium by activating phospholipase C, resulting in smooth muscle contraction, mydriasis, vasoconstriction in the skin, mucosa and abdominal viscera & sphincter contraction of the GI tract and urinary bladder
G-protein Coupled Receptors
G-protein can either open and close an ion channel or bind to adenyl cyclase, inducing formation of cAMP (2nd messenger)
Arachidonic Acid
second messenger (pain and inflammation)
Inositol tris-phosphate
second messenger (calcium release: third messenger)
Neuromuscular Junction
- thick basement membrane
- synaptic cleft is 100 nm wide
- junctional folds in motor end plate
- secondary clefts, expand junctional surface 5-6x
- increased number of receptors
- basement membrane contains AChE (cleavage)
- every AP results in muscle contraction
CNS Neuronal Synapses
- transmitter inactivation by cleavage or reuptake
- postsynaptic synapses - primary surface only
- thinner basement membrane
- synaptic cleft 20-50 nm wide
- often need multiple AP’s to generate post-synaptic response
- multiple receptor subtypes in one synapse
Lambert-Eaton Syndrome
pt. presents with muscle weakness and improved strength with repeated use; antibodies against voltage gated pre-synaptic calcium channels
Myasthenia Gravis
autoimmune disease in which the body makes antibodies against ACh nicotinic receptors; pt. presents with muscle weakness, inability to perform repetitive movements; symptoms most commonly begin in early adulthood; treated with physostigmine and neostigmine (AChE inhibitors); treatment involves removal of thymus gland, immunosuppressive drugs, and plasmapheresis
Botulinum Toxin
binds presynaptic membranes, preventing calcium-dependent exocytosis in PNS only and interfering with release of ACh; used to reduce spasticity, reduce excessive sweating, and migraines
Excitotoxicity
prolonged excessive glutamate release at injury site causes death of neurons; glutamate overstimulates NMDA receptors, causing massive increase of calcium inside the cell; calcium activates cell degrading enzyme cascades
CNS includes:
neural structures enclosed by bone; nerve roots, dorsal root ganglia, and spinal nerves
PNS includes:
neural structures not enclosed by bone; axons of sensory, motor, autonomic neurons, and cranial nerves
Types of Mechanical Injury to a Nerve
- compression
- stretch/traction
- laceration/transection
- electrical/thermal injury
Sites of Entrapment of Peripheral Nerves
- tunnels
- branches
- hard interfaces
- proximity to surfaces
- fixation to interfacing structures
Wallerian Degeneration
axon distal to injury deteriorates; deterioration of myelin and axon becomes disorganized, Schwann cells proliferate, phagocytose myelin & axonal debris; Schwann cells will form framework for regenerating nerve (if incomplete lesion)
Seddon’s Classification of Nerve Injury
- Neurapraxia: paralysis w/o peripheral degeneration
- Axonotmesis: axon damaged, but supporting cells intact
- Neurotmesis: axon and myelin sheath interrupted
Neurapraxia
local damage to myelin, secondary to compression; axon remains intact, but there is a local conduction block and the nerve loses its ability to propagate AP. Affects large-diameter fascicles, sparing smaller-diameter fascicles; motor fibers are lost first and recovered last, while pain and sympathetic fibers are lost last and the first to return
Clinical findings: complete motor paralysis, partial sensory loss
Axonotmesis
loss of continuity of axon with variable involvement of connective tissue elements, Wallerian degeneration occurs; retrograde and anterograde degeneration and loss of S&M function below lesion; Rate of regeneration = 1-3 mm/day (1” per month).
Clinical findings: complete motor & sensory loss
Neurotmesis
gross loss of continuity or internal disruption involving axon & connective tissue; regenerating axons may become entwined w/ fibroblasts & collagen. Prognosis depends on nature of injury & local factors (i.e. vasculature).
Clinical findings: complete motor & sensory loss
NCS: no motor unit potential response
Symptoms of Acute Nerve Injury
- paresthesia
- sensory symptoms before motor
- rapid onset
- short-lived, reversible symptoms
- intact pain & temp sensation
- reduced NCV
Symptoms of Chronic Nerve Injury
- paresthesia
- reductions/loss of touch/pressure
- muscle, weakness, atrophy
- pain, hyperesthesia, allodynia
- decreased or absent NCV
- insidious onset
Mechanoreceptors
monitor stretch; stretch and pressure receptors
Chemoreceptors
monitor chemical concentrations; carotid and aortic bodies, medulla, hypothalamus, stomach, taste buds, and olfactory buds
Nociceptors
monitor potentially harmful stimuli; viscera, arterial walls, and cutaneous
Thermoreceptors
monitor changes in temperature; hypothalamus and cutaneous
Solitary Nucleus relays information to:
visceral control areas in the pons/medulla AND hypothalamus/thalamus (limbic system)
Diabetic Autonomic Neuropathy
nerve disorder that affects involuntary body functions. Clinical findings include resting tachycardia, exercise intolerance, orthostatic hypotension, constipation, gastroparesis, erratic glucose control, loss of skin integrity, abnormal vascular reflexes, disruption of microvascular skin blood flow
Orthostatic Hypotension
a form of low blood pressure that happens when you stand up from sitting or lying down. Dysregulation of vasoconstriction of intramuscular arteries, blood flow to brain is decreased. Also, loss of vagal control so that vagal stimulation drops HR and blood pressure. Drop >20 systolic and >15 diastolic. Causes include bleeding, drugs (vasodilators or diuretics), dehydration, neurogenic orthostatic hypotension
Vasodepressor Syncope
strong emotion can cause vasodilation of the intramuscular arterioles leading to decrease in blood pressure. Can also have a vagal response leading to decrease heart rate which in turn leads to a further decrease in blood pressure.
Stellate Ganglion Lesion
stellate ganglion is a sympathetic ganglion formed by the fusion of the inferior cervical ganglion and the first thoracic ganglion, sympathetic influence to heart impaired
Horner’s Syndrome
lesion of the sympathetic outflow is on the ipsilateral side of the symptoms, can be result of disease, congenital, or iatrogenic. Symptoms include drooping eyelids, constriction of the pupil, skin vessel vasodilation with absence of sweating of face. MUST TREAT THE CAUSE
Horner’s Syndrome affects what three structures?
dilator pupillae (miosis), superior tarsal muscle (ptosis), and sweat glands (anhidrosis)
Acute Autonomic Dysreflexia
a reaction of the ANS that results from a spinal cord lesion above T6; associated with paroxysmal hypertension, throbbing headaches, profuse sweating, slow heart rate, and poor thermoregulation
Spinal Cord lesion above S2-S4 results in…
voluntary bowel and bladder control lost: reflexive control possible
Spinal Cord lesion at S2-S4 results in…
lack of voluntary or reflexive control of bowel and bladder (flaccid)
Neuroplasticity
input to a neuron induces a prolonged or permanent change in function, chemical profile and/or structure; changes can be macroscopic or microscopic, molecular or behavioral, adaptive or maladaptive, or short of long-term
Neural Development
Neurulation > cell proliferation > migration (mediated by the growth cone) and differentiation > axonal extension > synapse formation
Adhesive Substrate-Bound Cues
provide the “roadway” for the growing axon
Repellant Substrate-Bound Cues
provides the “guard rails” for the “roadway”
Synapse Formation
After recognizing target, growth cone sprouts processes, which form synapses. After contact, pre- and post- elements signal each other (retrograde signaling). The axon and target organ interact with and mature each other.
Synaptic Plasticity
changes in synaptic transmission, varying from msec to years; chemical = quick vs. structure = long-term
Habituation
decreased response to a repeated stimulus as a result of decreased synaptic activity between sensory neurons and interneurons, associated with decreased calcium influx; usually short-term and reversible effects depending on stimulus
Sensitization
intensified response to all stimuli, even ones that previously evoked little or no reaction; brain links painful stimuli w/ non-painful stimuli
Long-Term Potentiation
cellular mechanism for formation of memory in which rapid brief excitatory pulses enhanced synaptic efficiency (EPSP); glutamate binds to AMPA receptors, allowing sodium to flow into the cell and depolarize the cell. Magnesium unblocks the NMDA receptor, allowing calcium to flow into the cell and bind to calmodulin. This binding activates a cascade (kinase) resulting in increased gene expression (protein/receptor synthesis). These receptors move to the postsynaptic membrane, making it more susceptible to depolarization.
Glutamate binds with ____ receptors
AMPA
Calcium entering the postsynaptic cell membrane binds with _______
calcium
Spreading Depression
area surrounding the injury are also involved
Secondary Cell Death
cascades of physiological and biochemical reactions that lead to death of neurons, expanding areas of tissue damage
Presynaptic Changes After Injury
- increased transmitter release
- synaptic hyper-effectiveness
- sprouting of new axon terminals
Postsynaptic Changes After Injury
- denervation hypersensitivity (postsynaptic cell develops more receptors to compensate for decreased input and may receive messages it wasn’t originally intended to)
- receptor desentization
CNS Synaptic Changes After Injury
1) recovery of synaptic effectiveness
2) presynaptic changes
3) postsynaptic changes
4) disinhibition of silent synapses
Cortical Reorganization
- reorganization of sensory representation
- new areas take over tasks
- can be transient or long lasting
- may or may not be beneficial
How do bungarotoxin and curare work?
block binding of ACh to postsynaptic receptor
Norepinephrine Receptors: alpha-2
G-protein coupled receptor that causes decreased cAMP by inhibiting adenyl cyclase, resulting in smooth muscle mixed effects, norepinephrine (noradrenaline) inhibition, and platelet activation
Norepinephrine Receptors: beta-1
G-protein coupled receptor that causes increased cAMP by activating adenyl cyclase causing positive chronotropic, dromotropic and inotropic effects, and increased amylase secretion
Norepinephrine Receptors: beta-2
G-protein coupled receptor that causes increased cAMP by activating adenyl cyclase causing smooth muscle relaxation (ex. bronchodilation)
Neurogenic Orthostatic Hypotension
results from spinal cord disorders, peripheral neuropathies, and autonomic degenerative disorders (ex. MS)
