PATH II: Intro to Brain/Spine & Brain Organization, Glial Cells, APs and NTs

What are the divisions of the nervous system?

central nervous system and peripheral nervous system

What is included in the CNS and what is it covered by?

Brain, spinal cord, CN 1+2, and retina. Covered by meninges.

What is the cortex of the brain?

Neuron cell bodies on the surface

What are the two divisions of the PNS?

sensory (afferent) and motor (efferent)

What are the two divisions of the sensory division?

Somatosensory + Special Senses

What is the somatosensory division's purpose and location?

Pain, touch, etc.

What is the special senses' function and location?

Only in head like vision, scent, etc.

What does the motor (efferent) division of the PNS do?

Carries info from brain to tissue

What does the sensory (afferent) division of the PNS do?

Carries info from tissue to brain

What are the two systems of the motor division?

Somatic motor + autonomic motor

What does the somatic motor system do?

controls skeletal muscles

What does the autonomic motor system do?

controls smooth muscle/involuntary movements

What two divisions are there to the autonomic motor system?

Sympathetic (fight or flight) + Parasympathetic (rest and digest)

What two matters make up the CNS, what does each matter do, and where is each located in the spinal cord and brain respectively?

Gray matter = made of groups of cell bodies (nuclei/ganglia), found superficially in brain within the cortex or deep in the basal ganglia (e.g. thalamus) and internal in spinal cord as horns

White matter = myelinated axons (nerves/fibers), found deep in brain made of tracts called fasciculi and superficial in spinal cord

What are the three axon fiber types?

Projection, commissural, and association

What do projection fibers do and how do they travel?

Ascending tracts = sensory

Descending tracts = motor

What do commissural fibers do? What are the connections in the brain vs spinal cord?

Coordinate activity & Corpus callosum and anterior commisure (smaller)

What do association fibers do? How does each type connect?

Arcuate fibers = connect adjacent fibers

Longitudinal fasciculi = connect nuclei from sensory domains to decision making domains

List the spinal cord divisions and the general region each corresponds to.

cervical = neck, thoracic = chest, lumbar = hips/leg, sacral = tailbone

What are the spinal cord's functions?

Convey sensory/motor info to + from the brain and integrate sensory/motor info for reflexes within itself

Which sections of the spinal cord are enlarged and why?

Cervical and lumbar because of sensory/motor input from upper and lower limbs respectively.

Which nervous system has numbering for its nerves and how many are there?

31 PNS spinal nerves

What is a dermatome?

A spinal nerve responsible for sensory/motor info on an area of skin

Where does sensory and motor information enter the spinal cord respectively? Where are the somas of each root located and how does the information travel?

Sensory enters dorsal side, motor on the ventral. Soma of dorsal root is in dorsal root ganglia farther away from center column and info is carried from brain to tissue. Soma of ventral root is within the spinal column.

What is a fissure? Which ones do we know and what do they separate? (See blanked labeling photo from slides).

Deep furrow, lateral/sylvian fissure (temporal/frontal+parietal), medial longitudinal fissure (separates hemispheres), central sulcus (frontal and parietal lobe), notch (slightly temporal/occipital), calcarine sulcus (superior = cuneus/inferior = lingual gyrus)

What is a gyrus/sulcus?

Hill or ridge/valley

List the lobes and their functions

Parietal: somatosensory + visually where/how

Occipital: visual processing, perception, eye movement

Temporal: processing/perception of sound, understanding language, high order visual processing (faces/objects), meyer's loop

Frontal: Executive function, personality, motor behavior (speech), eye movement

What are the parts of the limbic system?

Amygdala, hippocampus, thalamus, hypothalamus

What is known as a sensory hub?

Thalamus

What are the functions of the limbic system?

Motivation, reward, emotions (fear+anger), memory formation+retrieval w/olfaction, and stress response.

Is the cortex homogenous? Why or why not?

No, it varies b/c of functional differences.

What are the mapped areas of the brain called and how many are in each hemisphere?

52 Brodmann areas

Which layers of the cortex are more abundant in sensory/motor?

IV/V

What are the functional cortices within the lobes?

Somatosensory, visual, auditory, prefrontal, motor

What are the association cortices within the lobes?

Parietal association cortex/Prefrontal association cortex

Which hemisphere does contextual language reside in?

Non-dominant

What lobes are responsible for contextual language and what are each lobe's responsibility? Are they motor or sensory?

Frontal (motor): imbues language with emotion

Parietal (sensory) interprets contextual language

What is the left parietal lobe responsible for in regard to visual field? What about the right parietal lobe? What would a lesion in these areas present as?

Left = attention to right side of world; no change

Right = attention to left and right side of world; ignore left VF or hemineglect

Is hemineglect sensory or perception based?

Perception

What are the glial cells and their function? Where are they present and What is their morphology?

Ependymal cells: Ciliated simple cuboidal epithelium lining ventricular spaces; choroidal plexus has specialized type that produces CSF

Microglia: Inactive = branching, active = like an APC. APC of CNS and migrate during early development.

Astroglia: star shaped. Regulate Na+/K+ in ECF of brain + remove, recycle and isolate NTs at synaptic foot processes + create BBB + regulate blood flow + create astrocytosis

Oligodendrocytes (CNS): multilayered wrapping of membrane of one cell around several axons (white matter). Speed up AP and secrete Nogo when damaged to inhibit growth cone.

Schwann (PNS): Similar to oligodendrocyte but 1 cell per axon. If injured do not make Nogo.

What is astrocytosis, when does it occur and why?

Astrocytes becoming reactive and filling in areas of injury (not collagen). If too large becomes cyst. This is because neurons do not regenerate (barring the hippocampus)

What is the smallest functional unit of the nervous system? What does it do, how is it named, what are the components of this unit, and what do the energy requirements look like?

Neuron, convey electrical impulses, named for type of neurotransmitter released (e.g. cholinergic), soma (body) + dendrites (receive info) + axon hillock (AP initiation) + axon terminus (terminal aborization for releasing NT)

What are the three general types of neurons, their shape, length, and characteristics? (Efferent/afferent/modulator/etc.)

Sensory/Receptors: Afferent, cell body within dorsal root ganglia, pseudounipolar, long

Motor: Efferent, long, unipolar

Interneurons: Tiny, no AP, modulate synapses

What cells have membrane potentials and why? Furthermore, what is synaptic transmission?

All for regulation of the activity of a cell/neuron. Communication between cells often involving a neurotransmitter.

What do the charges inside and outside of the cell look like during resting potential/action potential?

Resting: positive out, negative in (K+ is more relatively positive than Na+)

Action: negative in, positive out

How do the charges look during resting membrane potential, depolarization, and hyperpolarization?

Resting = difference between 0 and current state (typically neg)

Depolarization = less negative

Hyperpolarization = more negative

What are the ECF and ICF concentrations of Na, K, and Ca/Cl?

ICF Na = 15 mM

ICF K = 150 mM

ECF Na = 150 mM

ECF K = 5 mM

ISF Ca > ICF Ca

ISF Cl < ICF Cl

What are ions-elective leak channels and how do they relate to permeability?

Always open channels allowing specific ions down their gradients. They cannot be changed in number and determine the permeability of the cell.

Explain the equilibrium potential of K and Na

K:

1a.) K efflux from concentration gradient (major) and Cl accumulation = negative inside

2a.) K influx due to electrical gradient (minor)

3a.) K influx and efflux comes to equilibrium = Ek

Na:

1b.) Na influx due to concentration gradient (major)

2b.) Na efflux due to electrical gradient (minor)

3b.) Na influx and efflux comes to equilibrium = Ena

What is the Ek/ENa when ICF/ECF K = 150mM/5mM Na = 15 mM/150mM?

-91.6 mV and 62 mV

Draw out how membrane potentials would present under hypo/hyperkalemia/natremia and high/low Na/K ATPase activity. State the electrical state of the cell too.

See notes

Where on a neuron do resting, electrotonic and action potentials take place on a neuron?

Resting = all

Electrotonic = Dendrites/soma/axon termini

Action = axons

Draw on an action potential curve where the threshold, depolarization, overshoot, repolarization and hyperpolarization take place.

See notes

Explain the steps of continguous propagation

1. Threshold

2.) V-G Na+ channels open

3.) Na+ influx = depolarization

4.) + charge spreads to adjacent segments to bring them to threshold

5.) V-G K+ channels permeable

6.) K+ efflux = repolarization

7.) K+ channel slowly closes following hyperpolarization

8.) Brought back to resting membrane potential

What are the different types of propagation, their relative speeds, myelination status, and presence of V-G channels?

Contiguous: slow and non-myelinated

Saltatory: jumps from node of ranvier to node of ranvier, fast, and myelinated (where nodes are not present). V-G channels in nodes of ranvier, no V-G channels in myelinated areas. Leak channels span the whole neuron.

What are the different axon fiber types from fastest to slowest, their roman numeral/letter class and relative structures innervated?

Ia = Muscle spindle primary endings

Ib = Golgi tendon organs

A-alpha = Efferents to extrafusal muscle fibers

II = A-beta = muscle spindle secondary endings

A-gamma = Efferents to intrafusal muscle fibers

III = A-delta = pain/cold

B = Preganglionic autonomic efferents

IV = C = Most nociceptors and warmth

How does myelination and diameter affect AP speed?

Large diameter/myelin = faster

What is an absolute refractory/relative refractory period? What is the charge range of each?

Absolute refractory period: unable to fire AP w/ stimulation, threshold to -70 mV, and voltage gated channels Na+ channels are either open or closed, becoming reset once hyperpolarized.

Relative refractory period: can fire AP w/ HIGH stimulation, -70 mV to rest, weak AP if stimulus is strong enough that occurs after hyperpolarization because some channels have reset.

Which is more dangerous hyper or hypokalemia? Why?

Hyper because it depolarizes the cell, reducing the amount of charge required to reach the threshold, resulting in no absolute refractory period, persistently open Na+ channels, and consequently no AP ever again which results in death.

How does Proparacaine work?

Inhibits Na+ v-g chs

Which cells do demyelinating diseases such as MS or Guillain-Barre affect? How does this group of diseases affect the action potential?

MS = oligodendrocytes in CNS

Guillain-Barre = schwann cells

Demyelination -> Leak channels of demyelinated areas exposed w/ no v-g channels -> lose charge

Where are electrotonic potentials present and what are the specific functions of each?

Everywhere but axon.

Soma = allows cell to reach threshold

Synapse = regulate NT release

What are the functions of electrotonic potentials?

1.) Bring axon hillock to threshold

2.) Modulate amount of NT released from one axon termini

3.) May be the only potential on an interneuron

4.) Common potential of special sense cells

What is an EPSP/IPSP and generator/receptor/presynaptic potentials?

EPSP: depolarize membrane = closer to threshold of AP

IPSP: hyperpolarize membrane = farther to threshold of AP

Generator: somatosensory neuron electrotonic potentials

Receptor: special sense receptor electrotonic potentials

Presynaptic: axon termini electrotonic potentials

Does increasing/decreasing permeability to the following ions cause an IPSP or EPSP?

Na increase/decrease = EPSP/IPSP

K increase/decrease = IPSP/EPSP

Ca increase/decrease = EPSP/IPSP

Cl increase/decrease = IPSP/EPSP

What is temporal/spatial/cancellation summation? How do EPSPs and IPSPs interact similarly on the surface of a neuron?

Temporal: Neuron firing multiple APs over a given time, signals summate and keep ligand-gated ch open longer

Spatial: Multiple neurons sending multiple action potentials to one neuron's dendrites, resulting in summation and opening of several ligand-gated ch

Cancellation: EPSPs and IPSPs cancel out.

Soma can cancel an EPSP from dendrites via IPSPs

Compare and contrast ionotropic and metabotropic receptors.

Ionotropic: Faster and are receptor + ch

Metabotropic: Slower and are only receptor. More sustained signal d/t secondary messengers (for sustained muscle contraction like heart).

Explain the mechanism of dark current

1.) Dim light or darkness causes cGMP to be produced
2.) cGMP opens light-gated Na+ ch
3.) Na+ influx
4.) Depolarize cell (-40 mV)
5.) Cell excited
6.) Release glutamate onto bipolar cells

Write out the location, channels, ways one can change the potential of resting, electrotonic, and action potentials

Check notes for table (2b)

Compare and contrast chemical and electrical synapses based upon the following criteria:
a. Communication speed and method
b. Messenger usage
c. Affect on cell(s)

a. Chemical (slower across synaptic cleft unidirectionally) vs Electrical (faster across gap junctions bidirectionally and syncitium like)
b. Chemical (uses NT) vs Electrical (no NT)
c. Chemical (cause EPSP/IPSP) vs Electrical (cause electronic potential in post-synaptic cell)

Write out the steps of a chemical message across a synapse

1. AP in presynaptic fiber causes Na to spread into axon terminus and depolarize

2. Depolarized terminus opens v-g Ca+2 allowing influx into cell

3. Ca+2 allows synaptic vesicles to dock on SNARE ptns and empty NT into synaptic cleft (in quanta = 10k)

4. NT binds post-synaptic receptors (iono/metabotropic) and cause EPSP/IPSP quickly then unbind for recycling

What are the three mechanisms by which NT can be removed from the cleft after they have done their job?

1. Reuptake and recycling by post-synaptic cell

2. Uptake and recycling by glia

3. Degradation by enzyme (uncommon)

Which NT is most common overall? Is it excitatory or inhibitory? Furthermore, what type of NT is it and how is it made/removed?

Glutamate (Excitatory except retina where it is both)
Biogenic amine removed by reuptake transporters on astrocytes/presynaptic cell

What are the metabotropic, ionotropic, and voltage-gated receptors of glutamate and their function?

mGluR 1-6: rod regulation/visual cortex, can open or close cation ch
AMPA + Kainate: open Na+ channels and causes EPSPs

NMDA (v-g and ionotropic): open Ca+2 channels, need to be associated with AMPA or Kainate receptor

Write out the mechanism of NMDA

1. Glutamate in cleft binds and opens AMPA or Kainate and NMDA

2. AMPA or Kainate open allowing Na+ influx, weak local depolarization, and Mg+2 in NMDA expelled

3. OR NMDA opens (requiring v-g and ligand gating) = Ca+2 influx, depolarization, and 2nd messenger for long term potentiation

4. Glutamate removed

What is acetylcholine, where is it found, and what receptors does it have?

2nd most common excitatory NT found in somatic motor neurons as well as autonomic nervous system. The receptors are nAChR and mAChR 1-6

What is GABA, what receptors does it have, where is it found, and what are some agonists of it?

2nd most common NT and most common inhibitory NT found at interneurons with ionotropic GABA A receptors which are Cl- ch and metabotropic GABA B receptors. Some agonists include:
Benzodiazepines (Xanax/Valium)
Benzodiazepine-like (Ambion)
EtOH

What are catecholamines, which NTs do they include, what type of receptors do they have, and are they inhibitory or excitatory?

Group of NTs made from tyrosine that can be excitatory or inhibitory with metabotropic receptors. Includes dopamine, NorE, and E.

How is dopamine removed from the synaptic cleft and what does it do? Also, what receptors does it have?

Catechol-o-methyl transferase (COMT) and/or Monoamine oxidase (MAO). It is responsible for the following:
1. Mood, contentment, and reward from nucleus accumbens (limbic system)
2. Helps with initiating motor activity in basal ganglia and midbrain (e.g. Parkinson’s)

3. Regulation of prolactin release by hypothalamus

D1-5 receptors

What is the difference between norepinephrine and epinephrine? What kind of receptors do the lungs, eye, and adrenal medulla have? What receptors does NorE vs E prefer?

NorE is released from neurons while E is released from the adrenal medulla.
B2, Alpha/Beta 1+2
NorE = A1/2
E = B1/2

What are some of the shared characteristics of catecholamines?

Tyrosine is common substrate
All receptors are metabotropic

Degraded post-synaptically by COMT and presynaptically by MAO or reuptake channel
Rx/recreational drug effects

What is serotonin, what is it derived from, and what is its clinical importance?

Contentment and arousal NT made from tryptophan that is removed similar to catecholamines but reuptaken by SSR (serotonin specific reuptake).
Cocaine is reuptake inhibitor and so can COMTi/MAOi/SSRI

What is coding and give an example with a low intensity stimulus

Relationship between electronic potentials, action potentials, and synaptic transmission.
Low intensity stimulus
Low amplitude electrotonic potentials
Low frequency AP
Low quantal release of NTs

What is presynaptic inhibition vs facilitation? How does each affect NT release, the axon terminus, and synaptic transmission?

Inhibition:

Decreases NT release
AP depolarizes terminus

IPSP on axon terminus

Decrease polarization of terminus
Decrease synaptic transmission
Facilitation:
Increases NT release
AP depolarizes terminus
EPSP on axon terminus
Increases depolarization of terminus
Increases synaptic transmission