2b. Neurology

Examples of a ganglia in the nervous systerm include: A) dorsal root B) ventral root C) sympathetic D)A and C E) A, B and C

D

If a neuron has receptors for a particular neurotransmitter (NT), it will also ... A. bind to an antagonist of that NT. B. release that same NT at its axon terminals. C. respond in a similar way to an agonist of that NT. D. both a and c E. a, b and c

D

If you know that a neuron is releasing acetylcholine as a neurotransmitter, you can isolate it to what division of the peripheral nervous system? A. Somatic motor B. Autonomic C. Sympathetic D. Efferent E. Parasympathetic

D

Increased parasympathetic output to the following targets would ... A) Digestive tract - enhance digestion B) Muscles controlling pupil diameter - causes dilation of the pupil C) Cardiac muscle - decrease heart rate D) A and C E) A, B and C

D

Myasthenia gravis is an autoimmune disease in which nicotinic receptors at the neuromuscular junction are damaged by the immune system. The muscle weakness characteristic of this disease can be reduced by ... A. Treatment with an acetylcholine reuptake inhibitor. B. Treatment with curare. C. Treatment with the acetylcholine agonist muscarine. D. Treatment with an inhibitor of acetylcholinesterase.

D

Neurotransmitters can change membrane potential of the postsynaptic cell by binding to two different classes of receptors. These are ... A. Ligand-gated and voltage-gated receptors. B. Intracellular and cell-surface receptors. C. Purinergic and adrenergic receptors. D. Ionotropic and metabotropic receptors.

D

Release of neurotransmitter typically involves: a) action potentials arriving at the axon terminal or varicosity. b)opening of voltage-gated Ca2+ channels. c) IPSPs d) a and b e)b and c

D

The autonomic nervous system does NOT innervate which of the following: A. Exocrine and endocrine glands B. Smooth and cardiac muscle C. Adipose tissue D. Skeletal muscle

D

Which of the following is/are true about adrenergic beta receptors: A. Their antagonists will cause slowing of the heart. B. Ligand-binding causes rapid opening of ion channels C. They bind the drug isoproterenol with high affinity. D. a and c E. a, b and c

D

Which of the following is/are true about epinephrine: A. It is synthesized from an amino acid precursor. B. It is a neurotransmitter released by the parasympathetic nervous system. C. It is a hormone released by the adrenal medulla. D. a and c E. a, b and c

D

Cris & Sab Describe the Cholinergic Receptors of the ANS What acts on what? - Similar to? - *Excite or Inhibit?* - Mechanism?

*ACh acts on nicotinic receptors* at *all autonomic ganglia* - same type of receptor as *NMJ* - always *excitatory* >> Na+ channels --> Na+ entry --> *depol*arization *ACh acts on muscarinic receptors* at target cells of *para*sympathetic neurons - *GPCRs* - may open or close channels - *excitatory or inhibitory*

Distinguish convergence and divergence

*Divergence* is often in *efferent* nervous system pathways *Convergence* is often in *afferent* (sensory) NS pathways

What determines signal strength? Important details?

*Frequency of action potentials *arriving at presynaptic terminal is a major determinant of signal strength -- Top just barely reaches threshold = triggers Aps, but not so many Trigger zone and other area at dorsal root have same #! So *integrity of signal number despite location* Bottom is stronger signal so more APs so longer depol Frequency of APs are the language of measuring intensity of a stimulus (*amplitude are always the same*)

Cris & Sab Describe amino acids as neurotransmitters Prevalence? Examples? Excitatory or inhibitory? *Mechanism?*

*Most common* neurotransmitters (NTs) in CNS Examples: - *Glutamate* - major *excitatory* NT in *brain* - *Aspartate* - also *excitatory* - *GABA* (gamma-aminobutyric acid) - major *inhibitor* NT in *brain* - *Glycine* - main *inhibitor*y NT in *spinal cord* -- Both inhibitors *influence chlorine absorption*

Describe the importance of the vagus nerve

75% of parasympathetic fibres travel in vagus nerve - aka cranial nerve X

An adrenergic agonist would be a useful drug to take ... A. During an asthma attack B. As a digestive aid C. To slow down your heart rate D. To constrict your pupils E. Any of the above, depending on which receptor subtypes the agonist acts on

A

Describe the synthesis and recycling of ACh

AChE is the *off switch*, its on the extracellular surface of the post synaptic cell

Sab Main difference between AMPA and NMDA

AMPA mainly Na NMDA mainly Ca

Which of the following is/are correct about the autonomic nervous system? A) One limb is the sympathetic division, which involves long preganglionic neurons and short postganglionic neurons. B) One limb is the parasympathetic division, which involves long preganglionic neurons and short postganglionic neurons. C) It is under voluntary control. D) A and C E) B and C

B

Cris If a person's vagus nerve was severed in an accident, that person is likely to experience ... A. a slower heart rate. B. erectile dysfunction. C. digestive difficulties. D. a and c E. a, b and c

C

Place the following events regarding neurotransmitter release in the correct order: 1. neurotransmitter binds to its receptor 2. neurotransmitter is released into the synaptic cleft 3. Ca2+ influx 4. action potentials arrive at axon terminal 5. voltage-gated Ca2+ channels open Question options: A. 1, 2, 4, 5, 3 B. 2, 1, 4, 5, 3 C. 4, 5, 3, 2, 1 D. 5, 4, 3, 2, 1

C

Sab With respect to cholinergic receptors, which statements is/are true? A) Muscarinic receptors are expressed on motor end plates and parasympathetic postganglionic neurons. B) Nicotinic receptors act via G proteins and may be excitatory or inhibitory. C) Muscarinic receptors are expressed on effectors of parasympathetic pathways. D) A and C E) A, B and C

C

The following ion channels are required for transmission of information from the central nervous system to a skeletal muscle: A. mACh-R, Kv, Cav, nACh-R B. Cav, Kv, nACh-R C. Nav, Kv, Cav, nACh-R D. Nav, Kv, Cav, mACh-R -- nACh-R = nicotinic acetylcholine receptor mACh = muscarinic acetylcholine receptor Cav = voltage-gated Ca2+ channel, etc ...

C

The sympathetic branch of the autonomic nervous system is also referred to as ... A. The peripheral nervous system B. The somatic motor division C. The system mediating 'Fight or Flight' reactions. D. The 'rest and digest' system

C

The trigger for the opening of voltage-gated Ca2+ channels in an axon terminal is ... A. entry of Ca2+ into the terminal. B. binding of a neurotransmitter to the axon membrane. C. depolarization of the membrane of the axon terminal. D. a and b E. a, b and c

C

What is a characteristic of acetylcholine? A. It has different isoforms depending on the cell type and genetic differences between species. B. Its signal is inactivated by trnasport back into the presynaptic axon terminal for recycling. C. It is synthesized in the axon terminal. D. It is a modified amino acid.

C

What statement is FALSE about nitric oxide as a neurotransmitter? A. It as a very short half life. B. It mediates dilation of blood vessels. C. It is stored in vesicles in neuron varicosities, awaiting the depolarization release signal. D. Its synthesis is catalyzed by nitric oxide synthase.

C

Which of the following is/are true about NMDA receptors: A. They are inactive (closed) in a depolarized neuron. B. They are G-protein coupled receptors in the CNS. C. They are cation channels. D. They generate either IPSPs or EPSPs depending on the ligand. E. a and c

C

What is a neuromuscular junction?

Junction *(space) between somatic motor neuron and skeletal muscle* Many efferent terminals on the muscle from ventral Motor end plates connect to specially expressed regions of the myofibre

Sab Describe the glutamate pathway Main message

Left: Low freq of stim = low freq of APs Right: vv with sustained depol *Enhanced sensitivity in post and enhanced reactivity in pre synaptic cell* - MORE GLUT FROM PRESYNAPTIC CELL ACTING ON POSTSYNAPTIC CELL THAT IS MORE SENSITIVE TO GLUT

Sab One ligand one receptor? *examples*

More than one receptor for a particular ligand oNLY FOR SMOOTH VESSELS NOT SKELETAL

Describe Autonomic synapses (Varicosities) Secretors? Specific? Receptor density?

Postganglion neurons end in a series of '*varicosities' loaded with packets of neurotransmitter* *Receptors are not clustered near varicosities* - neurotransmitter enters interstitial fluid and *diffuses to receptors* - single postganglionic neuron can affect *large area of tissue* -- Non-myelanated Varicosities bulges draped over muscle cells in lots of areas, they *exocytose signal into ECF* to find receptors on smooth muscle cells. Good for *generalized response*

Describe NO as NTs Enzyme? Regulation? Half life? Effect?

Synthesized from oxygen & arginine catalyzed by enzyme *nitric oxide synthase* Very unstable, *short half life* (seconds) can't be stored in vesicles, *release controlled by regulation of enzyme* Best known effect is acting on vascular *smooth muscle to dilate blood vessels* aka endothelium-derived relaxing factor (EDRF) Nobel Prize 1998

Describe peptides as NTs Types? Examples?

Synthesized in the same pathway as proteins, in cell body, via rough ER Golgi transported in secretory vesicles down axon 85 different neuropeptides identified (so far) - neurotransmitters >> *Neuromodulators* (tweaking synaptic transmission), *neurohormones* (released by neuron into blood) Examples: - substance P (pain pathways) - opiate peptides (*endorphins*) - often secreted by a neuron along with a '*conventional'* NT

Sab Compare and contrast the two types of glutamate receptors

*Natural ligand* = glutamate *excitatory receptors *in CNS open cation channels - *ionotropic* --> fast EPSPs [Structure:] Must have *subtle differences at ligand binding site* since agonists are different *Ion selectivity*: AMPA-R lets in only Na+ and K+ (so mostly *Na+*) NMDA-R also lets in *Ca2+* *Voltage sensitivity*: *NMDA receptors are inactive at resting membrane potential* (*blocked by Mg2+ ion*) only open when postsynaptic cell is *already depolarized* -- *NMDA only open with strong and sustained depol* = Mg off = Ca influx

Describe Adrenal Medulla and the Sympathetic NS What releases what? "Neuron"? Does it secrete straight into bloo Long/Short Preganglionic fibers?

*Postganglionic sympathetic neurons release NE* as a neurotransmitter *Adrenal medulla releases E as a hormone* (since goes in blood) augments neural effects -- Medulla means "internal" *Adrenal medulla is considered a post ganglionic neuron* Example of *functional differentiation*

Sab Targets of the ANS?

*Smooth muscle* (vascular (*arterioles/veins*), gut) Exocrine *glands*, some endocrine glands *Cardiac* muscle

Cris & Sab Adrenergic Receptors of the Sympathetic NS What neurons? Secrete what? Bind to? Receptor types? Classified by? *Ionotropic or metabotropic?*

*Sympathetic / postganglionic neurons* Most *secrete NE*, binds to *adrenergic receptors* on target cells Two main receptor types, *α and β*, each with subtypes Classified according to *preference for NE, E and an agonist*: - β receptors distinguished from α - Receptors by their *sensitivity to isoprenaline* (isoproterenol; I) receptor types expressed in different cells / tissues -- Need to know this tables Show receptors that target cells express, *each have preference for difference hormones* *Beta prefer I, alpha do not* Adernergic affect symp post ganglion and are *metabotropic*

Ignore this slide

*[Electrical]* - *Current travels directly* between cells via *gap junctions* - Once thought to be very uncommon in higher animals - Growing appreciation of their importance during neural development and in adult brain - Very rapid communication, probably bidirectional, but no 'gain' *[Chemical]* - Molecules called *neurotransmitters* carry info from 'presynaptic' cell to 'postsynaptic' cell -- *Chemical can be modified* *Only certain types* of neurons have gap junction

Describe how synaptic transmission is modulated What makes more NT released?

1. *Post*synaptically: [] *Temporal and spatial summation* - multiple signals acting on target neuron 2. *Pre*synaptically: [] Change the *amount of neurotransmitter* released into synapse - *Depends on change in MP* at axon terminal >> *more depolarization more NT released* >> less depolarization less NT (just vv) -- >> APs arrive at terminal (depolarized) in a volley of spikes >> Open voltage gated Ca channels >> Ca influx >> NT release >> Longer terminal is open the more depol it is = more Ca out = more NT released

Describe the features of the autonomic nervous system Effector organs? - Solely by ANS? Activity level? Structure?

1. Activities normally *not under voluntary control* - autonomic *reflexes* that maintain homeostasis autonomous = acting independently or having the freedom to do so 2. Effector organs are *smooth muscle, blood vessels, glands, cardiac muscle* 3. Effector organs usually controlled by *both branches* - *antagonistic innervation* usually *some activity at all times* = *basal tone* 4. Structurally - *two efferent neurons* (ganglion) btw CNS and effector organ - *Preganglionic* (exit CNS) and *postganglionic* neurons

General overview of the NMJ to motor end plate connection?

1. Electrical *signal travels down* axon of presynaptic cell, to axon terminal 2. *Electrical signal converted to chemical* signal to cross gap 3. Chemical signal acting on membrane of postsynaptic cell *generates electrical response (fast) or activates second messenger pathway (slow)*

Cris The Nernst equation allows one to calculate ... A. the membrane potential that would result from the intra- and extracellular concentrations of a single ion to which the membrane is permeable. B. the membrane potential considering all the ions that are permeant across the membrane. C. the concentration of neurotransmitter that would be required to generate an action potential of a particular magnitude in the postsynaptic cell. D. the speed of propagation of an action potential along an axon as a function of the number of voltage-gated channels.

A

Cris & Sab Smooth muscle within most blood vessels is innervated by ... A) the sympathetic nervous system, acting via alpha-1 receptors. B) the sympathetic nervous system, acting via beta receptors C) the parasympathetic nervous system, acting via muscarinic receptors D) A and C E) B and C

A

Which of the following is an example of a parasympathetic response? A. Increased secretion of digestive enzymes into the lumen of the small intestine B. Increased heart rate C. Increased breakdown of fats stored in adipose tissue D. dilated pupils E. a and c

A

Give an examples of antagonistic control

Ach on muscarinic to stop NE(E) on adrenergic to speed up heart Both signals integrated for fine tuning

Sab Summarize the examples/*types of receptors*/location for amine and amino acid NTs Main types for amine? amino?

Amine = mainly GPCR w/ sero ion Amino = mainly ion

What are the locations of neuron-neuron synapses?

Axons of one to the dendrites of another

Cris A given neurotransmitter ... A. Always has both ionotropic and metabotropic receptors, depending on the target cell. B. Acts via ion channels or metabotropic receptors, or both, depending on which neurotransmitter. C. Acts on ionotropic receptors when released by the postsynaptic cell in low concentrations and on metabotropic receptors at high concentrations. D. Acts via either ion channels or metabotropic receptors, but never both.

B

If a tissue or organ has muscarinic cholinergic receptors, you know it is NOT ... A. smooth muscle in the digestive tract. B. skeletal muscle. C. lungs. D. cardiac muscle. E. smooth muscle in the bladder.

B

Ignore this slide

B

Describe disorders of synaptic transmission - Mechanisms? Treatment? Pros and cons of these diseases?

Bad news: *most vulnerable step* of neural signalling good news: neurotransmitter receptors face into extracellular fluid --> *accessible to drugs* 1. *Parkinson's disease* - *loss of dopamine-secreting neurons* --> provide more dopamine 2. *Schizophrenia, depression*, et al - Too much or too little of particular NTs in brain --> eg* not enough serotonin* --> inhibit its reuptake (*selective serotonin reuptake inhibitors*) 3. *Myasthenia gravis* - autoimmune *destruction of ACh receptors* at NMJ --> *inhibit acetylcholinesterase* --> gives ACh longer to act

Sab Drinking caffeine and your brain changes is an example of.... -- Other way synaptic transmission can be modulated? Resulting from? Example? - Name of process?

Changes in *structure*, *affinity* or *number* of neurotransmitter receptors These changes can result from *increased activity through a synapse* eg in the mammalian hippocampus: Intense communication btw two neurons leads to long-term enhancement of synaptic transmission between them (*Synaptic plasticity*) "*cells that fire together, wire together*" Donald Hebb and the Hebbian Synapse

Describe amines as a class of neurotransmitter Main class? Examples? Adrenergic neurons vs receptors? Modifications?

Derived from single amino acids - synthesized in axon terminal *Catechol amines* - *Dopamine* - *Norepinephrine* (noradrenaline) - *Epinephrine* (adrenaline) 'Adrenergic' neurons *secrete NE / E* 'Adrenergic' receptors *bind NE / E* Other amine neurotransmitters: *Serotonin* (5-hydroxytryptamine, 5-HT) (from tryptophan) *Histamine* (from histidine) -- *Minor subtle stepwise modifications* to make other neurotrnsmitters, they have *different affinities* for different receptors

An IPSP can be generated by ... A. binding of glutamate to receptors on the postsynaptic neuron. B. opening of Cl- channels C. closing of K+ channels D. binding of glycine to receptors on the postsynaptic neuron. E. both b and d

E

Epinephrine will cause ... A. dilation of blood vessels in skeletal muscle B. increase in heart rate C. constriction of blood vessels in the intestine D. a and c E. a, b and c

E

Increased sympathetic output to vascular smooth muscle serving skeletal muscle ... A. Would activate beta adrenergic receptors. B. Would cause the vessel to dilate C. Is a component of a fight or flight response. D. A and C E. A, B and C

E

Increased sympathetic output to vascular smooth muscle serving skeletal muscle ... A. Would activate beta adrenergic receptors. B. Would cause the vessel to dilate C. Is a component of a fight or flight response. D. A and C E. A, B and C

E

The adrenal medulla A) Is innervated by a long preganglionic fibre B) Are considered to be modified postganglionic sympahtetic neuron C) Releases epinephrine directly into the blood D) A and B E) A, B, C

E The long symp for adrenal medulla is a special example just for it

Distinguish between fast and slow synaptic responses

Fast: *Ionotropic* - Ion *channels open* directly Slow: *Metabotropic* - Signal *transduction*

What turns off NT signals? Options?

Ligand (NT) binds to protein (receptor) *is reversible* - *Stable equilibrium* btw bound and unbound ligand To *encourage dissociation of NT from receptor* must remove unbound NT from cleft by *dropping concentrations in the gap* Options: 1. NT removed via *uptake* into presynaptic terminal - Can then be *recycled into vesicles* or degraded eg epinephrine 2. NT *broken down* by enzymes in cleft - eg ACh - acetylcholinesterase (AChE) - *specific to synapse* - peptides - nonspecific proteases - *non specific* 3. NT *diffuses* away from synapse -- Glial cells can help clean up

Describe purines at NTs Types? Receptor locations?

Nucleotides that act as neurotransmitters adenosine, adenosine monophosphate (*AMP*), adenosine triphosphate (*ATP*) Bind to '*purinergic*' receptors in *CNS* and other excitable tissues

One NT for one particular effect? Examples? Significance?

One neurotransmitter *several different receptors* Examples: - *cholinergic receptors* >> nicotinic(ligand-gated ion channel with ACH as ligand *ionotropic*), >> muscarinic (ACH ligand but *metabotropic*) (5 subtypes) - adrenergic receptors - α1, α2, 1, 2, 3 - serotonin receptors - at least 20 types Significance: *allows one NT to have different effects in different tissues* Example: *Epinephrine* (E), *fight or flight* acting via ... - α1 receptors in blood vessels in skin constriction - b1 receptors in heart raises heart rate - b2 receptors in lungs bronchodilation

The cell bodies of the pregang in parasymp are found...

Sacral and brain stem

Summarive NMJ in consideration of ANS contraction in smooth muscle

Set up to always get some kind of contraction Compared to autonomic where its fine tuned with gradients and levels

Describe glutamate receptors two types? prevalence?

Several different types of glutamate receptors, two are involved in 'long-term potentiation' AMPA receptors: '*norma*l' glutamate receptors agonist: AMPA NMDA receptors: '*special*' glutamate receptors agonist: NMDA -- AMPA are strongly stimulated by AMPA, often in area where *moderate traffic* NMDA are strongly stimulated by NMDA, often in areas where *high traffic*

How do smooth junctions compare to skeletal NMJ?

Smooth varicocity spread vs direct *Dont always cause action potential* vs always Smooth always metabotropic vs nicotinic

Describe function/structure of NMJ

Sophisticated interaction Compare to varicosities

Describe NTs and receptors in the ANS What does symp use? parasymp? NTs and receptors at the ganglion for S/PS? NTs and receptors at the target for S/PS?

Symp via spinal nerves Para from brain stem or spinal chord So at Ganglion similar, but post ganglion very different

Describe ACh as a class of neurotransmitter Name of drugs that use it? Subtypes of receptors? - Type/Location/Agonists+Antagonists?

Synthesized from choline & acetyl CoA in axon terminal '*cholinergic*' - using ACh - *Neurons* that release ACh - *Receptors* that bind it - *Drugs* that mimic effects or trigger release of ACh 1. Nicotinic - Ionotropic Na+ - Skeletal muscle (NMJ) - Agonist is *nicotene* - Antagonist is *curare* 2. Muscarinic GPCR

Ignore this slide

Transgenic mice *lack of NMDA receptors* or downstream mediators of Ca effects *disrupts spatial learning* Young (but not adult) mice have a type of NMDA receptor that *stays open longer* ... CREATES *SMARTER MICE* (memory-wise)

Describe the effects of sympathetic and parasympathetic NS on: [] pupil [] heart [] lungs [] digestive tract [] bladder [] arterioles,veins [] adrenal medulla [] kidney [] adipose tissue

Urine is paradoxically For bottom table, sometimes we want blood away from certain areas and towards other areas

Compare the efferent pathways ANS Fibre length? Location? Ganglion? Effectors?

[Sympathetic:] - *Short pre*ganglionic fibres, - Sympathetic *ganglia close to CNS* - Originate in *spinal cord, thoracic and lumbar regions* - *Long post*ganglionic fibres to effector organs [Parasympathetic:] - *Long pre*ganglionic fibres, - Originating in *brain stem (travel in cranial nerves (vagus nerve) and sacral spinal cord*, - *Ganglia far from CNS* - *Very short post*ganglionic fibres

Ignore this slide -- a) Why so many different neurotransmitters (Ach,NE(E)) and receptors (AchNic/Musc) + Adreneric? b) Why do sympathetic and parasympathetic pathways release different NTs at target cells? c) Why are there different receptors for the same ligand? d) How can a system be controlled if it is only affected by one branch of the ANS?

a and b) All different NTs and receptors for fine tuning c) E/NE on vessels for certain ones dilate and certain constrict d) Basal tone

Cris & Sab List Agonists and Antagonists of ANS (with what releases what and receptors too) Predict the effect of atropine ... Famous (ab)uses of propranolol?

a) Parasymp is breed greed, blocking this means make you go symp (dilate pupils for visual exams), increases HR (if crashing in ER) b) Block symp, chill out, reduce BP

Identify the parts of the image

a) Schwann Cell b) Axon terminal c) Mitochondrion d) Vesicles with neurotransmitter e) Synaptic cleft - Tight connection (nanometers) f) Muscle fiber

Describe the consequences of inactivation Example? What would be the effects of inhibiting AChE activity?

eg. neuromuscular junction, failure to inactivate Ach = *cant turn off signal* situations in which this occurs: poisoning with organophosphate pesticides venoms, '*nerve gases*'