Final - Lecture 3

Tapping tendon stretches quadriceps, which sends signal to spinal cord, which causes quadriceps to contract

Fibers that are parts of muscle spindles

No, it is after the spindle, but before the myelinated axon

20-50

Propagated potentials

Heteronymous or synergistic

Graded receptor potential on sensory neuron in muscle spindle leads to action potential (receptor potential) to graded synaptic potential on motor neuron then action potential/receptor potential, then graded synaptic potential on the muscle then action potential/receptor potential

In their amplitude and duration

In their number and timing

Glass capillary microelectrode; tip is so thin that it can penetrate a neuron's membrane, allowing measurement o f the electrical potential across the membrane

The synaptic potential that determines whether or not the signal is propagated; technically, receptor potential is the first one, (such as on the muscle fiber) and synaptic potential is on every neuron from there on out

Sensory neuron also synapses on inhibitory neuron, preventing flexor motor neuron from firing

Hamstrings

Hyporeflexia ; problem with muscle, spond, motor or senssory axon

Hyperflexia; problem with uppe rmotor neuorn

Dorsal is where afferet sensory comes in; ventral is where motor efferent neuron goes out

Gray: cell bodies and dendrites
White matter: myelinated axons

BUndles of sensory axons that joing together before entering the dorsal horn

Bundles of motor axons that join together to exit the ventral horny

Towards the head and bottom respectively

Cervical: neck and arms (8 segments)
Thoracic: trunk (12 segments)
Lumbar: legs (5 segments)
Sacral: lower back , genitals (5 segments)

- Somatic are direct relays from central nervous system to skeletal muscle
- Central nervous system sendmessage along preganglionic fiber to autonomic ganglion, which relay messages along postganlionic fiber to glands, organs, and smooth muscle

1. Location of ganglia: In sympathetic, ganglia are far from target and postganglionic fiber is long; in parasympathetic, ganglia is close to target and postganglionic fiber is short
2. Segmental origin of preganglionics: Sympathetic are in thoraci and lumbar; parasympathetic are in cranial and sacral
3. Nuerotransmitter: Sympathetic release norempinephrine and parasymapthetic release acetylcholine

1. Sensory/respond
2. Sepcailized cells
3. Neurons (such as hydra, jellyfish, & starfish)
4. Centralization: bringing neurons together in middle of animal to interactin, such as flatworm and planaria
5. Segmentation: assembling rest of neurosn into groups to control corresponding poarts of obyd, such as roundworms
6. Cephalization: putting a lot of neurons at the front of animal, such as roundworms, insects
7. Brain

Neural crest

Forebrain: prosencephalon
Midbrain: mesencephalon
Hindbrain: Rhombencephalon

Teh rostarl portion

Respiration, circulation, posture, and other "maintenance" functions

Muscle and reflex coordination

Auditory and visual centers, especially "unconscious" vision, such as oculomotor reflexes, motion sensitivie, and startle responses

Unconscious drives

Cranial nerves

Oculomotor and Trochlear

Vagus

Initiate and execute movement

German neurologist whose anatomical study revelaed differences in neuron shape, size, and arrangement among different areas of the brain; some sharp boundaries and differences among layers within areas

Trained rats to perform tasks then surgically removed or damaged particular portions for their cerebral cortex then tested their memory; that behavior declined gradually with amount removed, but it didn't matter much which parts were removed; led him to propose the Laws of Equipotentiality and Mass Action

French neurologist who took note of ability of people to recover considerable function after brian lesions, suggested specific mental abilities broadly disturbed in the brain

Karl Lashley and Cahrels Brown-Sequard

Proposed "homunculus" based on local stimulation during surgery for intractable epilepsy; led to distinct sensations, movements and even memories

1. Lesions studies
2. Direct stimulation
3. fMRI or PET scanning
4. Recording form neurons with a microelectrode
5. Multi-unit recording: recording hundreds/thousands of neurons at a time

Formed field of "electrophysiology"

6-8 nm

Brownan influex

1. Ions in nervous system rather than electrons
2. Current flows mainly across membranes rather than down wires
4. Electrical signaling in nervous system is related to changes in the membrane potential

K+ has fewer bound water molecules due to its less localized charge field

Same constituents, but the outside is 20 times more diluted than the inside

K+ selective chanels are impermeable to anions, so K+ leaves the cell to flow down its concentraton gradient; the inside gets a net negative charge which increase dramaticlaly as K+ ions flow out until concentration gradient is ocounterbalanced by K+ attracted to teh isnide by the electrical gradient

when its concentration gradient and the electrical gradient are equal and opposite

Drop the membrane potential 100mV

About 36 billion

Eion = TF/zF ln[Cout]/[Cin] = 60 mV log [Cout]/[Cin]

Out/In/Eq. Pot.
K+ = 5 mM/100 mM/-80mV
Cl- = 150 mM/13 mM/-65 mV
Na+ = 150 mM/15 mM/62 mV
Ca2+ = 2 mM/0.0002 mM/123 mV

60 mV/10fold change in Ko

The permeability to Na+ and Cl- is negligible, so the equation reduces to Nerst

Used to determine the resting potential in a neuron

RT/F ln (PK[Kout] + PNa[Naout] + PCl[Clout])/(PK[Kin] + PNa[Nain] + PCl[Clin])

Eion = RT/zF ln[Cout]/[Cin]

z = valence of ion
F = Faraday constant

In glial cells, the permeabilities of Na+ and Cl- are negligible, so the equation reduces to Nerst

1:0.025:0.45

The permeability to Na suddenly increases

Cell would be clamped at a negative membrane potential ~ lead to an inhibitory response

Nerst reaches eqilibrium; GHK reaches steady state, but not an eqilibrium condition

Used to pump Na+ out and K+ back into neurons

Sends 3 Na+ out for 2K+ in ~ maintains the negative c oncentration gradient

Ik = gK (Vmemb - Ek)

Electrical "driving force" is hte difference between the membrane potential (Vmemb) and the ion's equilibrium potential (Eion)

Yes

Single long polypeptide, 12 times more permeable to Na than K; domains, each with 6 transmembrane alpha-helixes (S1-S6)

S4

Depolarization opens channel and then inactivates it with a certain delay; repolarization to Vrest de-inactivates the channel & it is closed

Na+ channel blocker

Tetrodotoxin, lidocaine, saxitoxin, scorpion toxin

Red tide, like TTX

Blocks entry into pore from outside

Blocks pore from inside

Blocks inactivation step

9, 21, and 78

New congenital diseases associated with mutant ion selective channel genes, including certain neurological conditions with seizures and migraines

Absolute is when falls down to lowest; relative is rises from lowest to resting

2 milliseconds

0.2 meters/sec ~ 120 m/s

Axon caliber increases, so velocity increases

Changes conduction velocity & opening voltage-gated channels is the most time-consuming part of conduction, so the more distance that can be covered without channel opening, the better

1. Capacitance (ability to hold a charge) - decreasing capacitance would increase speed of conduction
2. Membrane resistance - increasing membrane resistance would increase speed of conduction
3. Internal resistance - decreasing internal resistance would increase conduction

Decreases capacitance and increases membrane resistance

Along the nodes of ranvier, which are not covered by myelin; that is where Na+ channels are concentrated

Along internodes

1. Chemical synapses
2. Syncytial synapses
3. Electrical synapses

Muscle fibers are formed by the syncitial fusion of many myoblasts

A minority of neurons; in epithelia for "metabolic cooperation"

Gap junction bridged by connexons

Connexins

Yes; permeable to molecules with a MW <1000

About 20 nanometers wide

Light microscopes cannot distinguish objects closer than about 200 nanometer apart

Cap nerve terminal & provide myelin in PNS

Provide myelin in the CNS

Space filler

Excitatory: large active zone
Inhibitory: small active zone

Type 1: Excitatory
Type II: Inhibitory

Type I: Prominent presynaptic dense projections
Type II: Less obvious presynaptic dense projections

1. QUantal hypothesis: released in "packets" of fixed size
2. Vesicle hypothesis: synaptic vesicels rare structural basis of quanta
3. Calcium hypothesis: voltag-edependent calcium entry couples stimulation to secretoin
4. SNARE hypothesis: interaction between SNARE proteins on vesicle and on presynaptic membrane, modulated by calcium, lead to vesicle fusion

Set stage for SNARE hypothesis, which is the molecular basis of other three hypothesises

Excitatoyr postsynaptic potential (EPSP) at neuromuscular junctions

5-10,000

Many mepps (quanta) released simultaneously

m = n * p
n = number of quanta available for release
p = probability that any quantum will be released upon stimulation

Presynaptic

Decreases quantal size and therefore response to transmitter

1. Numerosu vesicles in nerve terminals
2. Omega figures seen if the nerve is fixed very shortly after it is stimulated
3. Prolonged, intense stimulation leads to depletion of vesicles

Used as a vesicle recycling tracer

Synaptobrevin

SNAP-25 and Syntaxin

Botulin cleaves synaptobrevin (v-snare), SNAP-25, and Syntaxin
Tetanus toxins cleave Synaptobrevin

[Ca2+]^4, so a 2 fold calcium increase leads to a 16 fold release of quantal content

Speeds vesicle release when it binds calcium

Across the cleft: less than 1 microseconds; out of the cleft: 1 milliseconds

Second messengers

Ligand gated, such as AChR

Venom component that blocks the AChR

2

5 subunits, each with 4 membrane-spanning domains; M2 domains line the pore

Due to negatively charged amino acids lining hte pore

Enables an investigator to hold constant the membrane potential of a patch of membrane while current through a small number of membrane channels is measured

The postsynaptic response

TTX inhibit AP channels; alpha-BTX inhibit AChR channels

Myasthenia gravis

Muscle relaxant in surgery; not cleaved easily by AChE ~ causes desensitization (keeps AChRs open)

Ionotropic:
1. AMPA Receptor
2. Kainate Receptor
3. NMDA Receptor
Metabotropic
1. G-protein coupled

Voltage and Ligated Gated; lets Ca++ enter during large depolarization

GABA "A" in the brain and Glycine in the spinal cord

M2 is neutral or positively charged in GABA/Glycine receptors

Cause gCl- to increase, drivign the cel to ECl, whichi s close to the resting potential ("shunting" - Cl- influex counterbalances Na+ influex of excitatory synapses)

Strychnine

Picrotoxin

Rigidity, convulsions, seizures

Benzodiazepines, barbiturates, alcohol

STartle disease in which there is an exaggerated response to sitmuli, such as noise, due to small single amino acid mutationsin glycine receptor

Na & K

Na, K, and Ca

The increased size of the second of two closely-spaced synaptic potentials

Calcium enters to trigger transmitter released, then it is quickly removed. When the second stimulus is soon after the fist, "new" calcium enters before the initial pulse is fully removed; a little can make a big difference, because quantal content is proportional to [Ca2+]^4

The decreased size of synaptic potential with repetitive stimulation (often at high frequency) as a result from depletion of readily released vesicles (n)

10% (2000 GPCRs)

Affects one of the 3 intracelluar domains (alpha, beta, and gamma). For example, alpha can split from beta and gamma, move along the membrane, interact with other proteins, and active or inactive them

A secon dmessenger that activates protein kinase A, which activates many proteins, including channels

1. Amplification
2. Multiple effects: different GPCRs exert different effects ont he same enzyme
3. Subtle effects; second messengers can open or close channels, or change their voltage sensitivity or open time
4. Multiple messengers: GPCR can affect production of multiple second messegners
5. Multiple target

1. Sutherland
2. Fisher
3. Krebs
4. Rodbell
5. Gilman
6. reengard

Serotonin is the neurotransmitter at this axo-axonic synapse. It activates its receptor, a GPCR, leading to cyclic AMP, activating protein kinase A, inactivating potassium channel that terminates the action potential, so nerve terminal stays depolarized longer, calcium channels remain open longer, more calcium enters, and more neurotransmitter is released

A burst of high frequency stimulation (sometimes called a tetanus) can lead to a long-lasting increase in the size of the EPSP, which can sometimes last last for hours and/or occur heterosynatpically; involvedi n memory

2 diffrent types of glutamate receptors: activaiton of NMDA recetors leads to influx of enough calcium to activate enzymes that in turn lead to insertion of more AMPaA receptors, thereby increasing the EPSP size

Synaptic depression

Heterosynaptic facilitation

Synthesized from choline and acetyl CoA by cholin acetyltransferase (ChAT), packaged into vesicles by a transporter, released, interacts with receptors, brokwn down to choline and acetate by acetylcholinesterase (AChE), loaded by into cell by cholin transporter

Serves as acetylcholinesterase inhibitor to treat myasthenia gravis

Tensilon, organophosphate insecticides, nerve gas

Glutamate

Tyrosine

Tryptophan

Increases synthesis of DA

Stimulation of release of DA at nerve terminal

Inhibit breakdown of dopamine

Inhibits reuptake of DA

Inhibit reuptake of DA

Inhibit reuptake of seratonin

Paxil, prozac, Zoloft, celeza

Stimulate serotonin receptors ars partial agonist

GCRs in the brain

Heroin, morphine, codeine, enkephalins

Sleep