Exam I Flashcards

1
Q

Confirmation of hypotheses in science require what two related things?

What major feature of a neuron is critical for its function?

A

Confirmation of hypotheses in science require advancement of techniques and improving our resolution of analysis.

Neurons are highly polarized, a feature that is critical for their function.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Na channels accumulated where? Action potentials initiate where?
_____ has increased the pace of neuroscientific discovery and is probably the most common technique used in research today.

What is GFP?

A

Na channels accumulated at axon initial segment and action potentials initiate at AIS.

Fluorescence-based imagining has increased the pace of neuroscientific discovery and is probably the most common technique used in research today.
GFP is a non-toxic protein fluorophore.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

There is evidence for a ‘filter’ at what part of the axon? What does this filter do and therefore play a role in?

A

There is evidence for a ‘filter’ at the axon initial segment of neurons that restricts diffusion of certain proteins potentially playing a role in neuronal polarization.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What things determine the membrane potential of a neuron?

The resting membrane potential of a neuron is determined primarily by ____, and therefore is close to what?

A

Ion distribution and permeability determine the membrane potential of a neuron.

The resting membrane potential of a neuron is determined primarily by potassium channels, and therefore is close to the Ve(K+) or EK, the potassium equilibrium potential.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Different _____ are involved in controlling subthreshold and supra threshold depolarization.

___ channels are expressed at the Calyx of Held terminals, which have an unusual ___ and determine the _____.

A

Different ion channels are involved in controlling subthreshold and supra threshold depolarization.

KCNQ5 channels are expressed at the Calyx of Held terminals which has an unusual hyperpolarized activation voltage and determine the resting membrane potential.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Different _____ are uniquely suited to studying aspects of neuronal excitability and function.

Ion channels are highly diverse and exhibit unique properties which have largely been elucidated using ____ and ____.

Imaging methods have big advantage in imaging what?

A

Different neuronal recording techniques are uniquely suited to studying aspects of neuronal excitability and function.

Ion channels are highly diverse and exhibit unique properties which have largely been elucidated using current recordings in neurons and expression systems.

Imaging methods has big advantage in imaing multiple compartments and small structure (axon terminals, spines).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What three methods have been used to stimulate neurons? Briefly describe them.

A

Electrical stimulation, uncaging, and optogenetics have been used to stimulate neurons.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Compare/contrast current recordings vs. imaging methods vs. electricalstmulaion. e.g. what kinds of techniques for each and what are they best for studying?

A
Current recordings (patch-clamp, voltage-clamp, whole-cell,...) - best for studying ion channels.
Imaging methods (genetically-encoded indication, two-proton fluorescence..) - best for studying compartments and small structures e.g. axon terminals, Ca2+, spines).

Electrical stimulation, uncaging (photoactivation), optogenetics - best for neuron stimulation.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Chemical synapse & electrical synapse are two main what?

Briefly explain an electrical synapse.

Chemical synapses have what morphology, and found where? In regards to direction, how can chemical synapses propagate a signal?

A

Chemical synapse & electrical synapse are two main modalities of synaptic transmission.

Electrical synapse is a symmetrical electrically conductive link between two neighboring neurons that is formed at a narrow gap between the pre- and postsynaptic neurons known as a gap junction.

Chemical synapses are asymmetric morphology with distinct features found in the pre- and postsynaptic parts. Chemical synapses can only prop info from pre- to post-synaptic neuron.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Ribbon synapses occur where? (2)

A

Ribbon synapses occur where synaptic exocytosis is evoked by graded depolarization and where signaling requires a high rate of sustained release.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

The process of synapse development can be roughly divided into what4 steps?

____ proteins are critical players throughout synapse development and mediate what 4 things?

A

The process of synapse development 4 steps: 1) Initial contact, 2) Induction/ Differentiation, 3) Maturation and 4) Maintenance/ Exchange.

Trans-synaptic proteins are critical players throughout synapse development mediating: initiation, specificity, adhesion but also mature function.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

_____ composition changes during maturation.

Due to chloride cotransporters changing, what 2 things occur during development?

A

Postsynaptic receptor composition changes during maturing.

Due to chloride cotransporters changing, post-synaptic chloride concentration decreases during development, and GABA/Glycine activation switch from depolarizing/excitatory to hyperpolarizing/inhibitory.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Trans-synaptic proteins are critical players throughout _____.

Due to _____, post-synaptic chloride concentration decreases during development, and GABA/Glycine activation switch from ____ to _____.

A

Trans-synaptic proteins are critical players throughout synapse development mediating: initiation, specificity, adhesion but also mature function.

Due to chloride cotransporters changing, post-synaptic chloride concentration decreases during development, and GABA/Glycine activation switch from depolarizing/excitatory to hyperpolarizing/ inhibitory.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Briefly describe classic neurotransmitters (what are they, where are they synthesized/released? what do they do?…)

There are many different types of neurotransmitters with different release mechanisms. How many different kinds of neurotransmitters can a neuron can release?

A

Classic neurotransmitters are endogenous chemicals that synthesized and released by the presynaptic neuron and causes action on the postsynaptic neuron through receptors.

There are many different types of neurotransmitters with different release mechanisms. A neuron can release more than one neurotransmitter.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

The Neuron Doctrine was pioneered by whom and states what?

A

The Neuron Doctrine was pioneered by Ramon Y Cajal and states that the brain is made up of independently functioning cellular units called Neurons.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What 2 neurotransmitter gradients 2 transport mechanisms exist and what can they modulate?

A

2 transport mechanisms are Na+/H+ exchange or cation/H+ exchange.
2 neurotransmitter gradients: extracellular to cytoplasmic and then to vesicular. Extracellular-intracellular concentration gradient for synaptic vesicles (intracellular NT concentration is ~ 1-10mM lower (level?)). Can modulate synaptic transmission

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

At what concentration level is the cytoplasmic neurotransmitter and to what does this contribute?

Cytoplasmic sodium modulates what?

Cytoplasmic neurotransmitter concentration regulates what? (And at what location?)

A

Cytoplasmic neurotransmitter is at 1-10 mM level and contributes to stronger synaptic transmission.

Cytoplasmic sodium modulates vesicular glutamate transport.

Cytoplasmic neurotransmitter concentration regulates vesicular cycling at a GABA synapse.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What controls the pre-synaptic action potential waveform? What does the pre-synaptic action potential waveform determine?

Exogenous Ca 2+ buffers are used to mimic what and study what?

A

Different ion channels control the pre-synaptic action potential waveform, which determines calcium channel activation and Ca 2+ influx.

Exogenous Ca2+ buffers are used to mimic endogenous Ca2+ and used to study the coupling/distance between Ca 2+ channel and Ca2+ sensor.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Modulating the presynaptic Ca is efficient to control what?

Synaptic vesicle release includes what three principal steps?

Different proteins, known as _____ are involved in each step of synaptic release. ______ is the calcium sensor.

A

Modulating the presynaptic Ca is efficient to control the synaptic transmission strength.

Synaptic vesicle release includes three principal steps: docking, priming, and fusion.

Different proteins (SNAREs) are involved in each step of synaptic release. Synaptotagmin is the calcium sensor.

20
Q

Modulating ____ is efficient enough to control the synaptic transmission strength.

What is used to mimic endogenous Ca2+ and used to study the coupling/distance between Ca 2+ channel and Ca2+ sensor?

A

Modulating the presynaptic Ca is efficient to control the synaptic transmission strength.

Exogenous Ca2+ buffers are used to mimic endogenous Ca2+ and used to study the coupling/distance between Ca 2+ channel and Ca2+ sensor.

21
Q

Why can a conventional microscope not be used to study vesicle release? What must be used/done instead?

A

We cannot use a conventional microscope because the proteins and ions involved are too tiny. We must use EM and make indirect conclusions. Endogenous Ca buffers can be mimicked

22
Q

What was the hypothesis for JC 1and why?

A

They hypothesized that target-specific signals are involved in the development of the large Calyx of Held synapse because the MNTB is innervated by large calyx-type synapses, whereas the LSO, a neighboring auditory nucleus, receives much smaller excitatory synapses.

23
Q

What methods were used for JC 1? (Which animal model and what 3 techniques?)

A

Animal models- mice and rat; BMPR1a/1b cDKO mice.
cDNA- synthetic DNA transcribed from specific RNA through enzyme reactions.
qPCR-uses linearity of DNA amplification to determine amounts of a known sequence in a sample. (Fluorescent agent allows for measure of DNA generation).
ChIP- chromatin immunoprecipitation assays- identify links between genome and proteome by monitoring transcription through histone modifications.

24
Q

Using ISH and IHC, what results were found in JC 1?

A

BMPS play a role in guiding development in the calyx of Held. Deficits in function and morphology in BMP cDKO suggests a role for BMP signaling in the development of calyx of Held synapses, showed fast-transmitter release properties, and larger calyx growth.

25
Q

Using transmission electron microscopy (TEM), what results were found for JC 1? What explanation do the authors suggest?

A

Smaller calyces and fewer docked vesicles were seen in the BMPR KO mice. Calyx-type terminal in KO mice are smaller and have less active zones.
The authors suggest that fewer docked vesicles could explain the decrease in readily releasable pool and smaller release probability in EPSC recordings.

26
Q

For JC1, using IHC & electrophysiology, what 3 BMP signaling roles were discovered? What happened in the absence of BMP signaling?

A

These findings suggest a role for BMP signaling in:

  1. calyx growth.
  2. developmental increase of synaptic strength.
  3. synapse elimination at the developing Calyx of Held synapse.

Without BMP signaling, multiple innervations persist up to P10, and developmental acquisition of synaptic strength is delayed

27
Q

BMP family is a a candidate for specifying large synapses. BMPR1a/1b cDKO mice had what 4 features?

A

BMPR1a/1b cDKO mice had:

  1. Reduced nerve terminal size with fewer active zones.
  2. Failure of the elimination of competing synaptic inputs.
  3. Deficit in developmental acquisition of fast-transmitter release speed and high release efficacy.
  4. Slowing in the decay of quantal EPSCs
28
Q

BMP signaling initiates what 3 major processes? These together do what to the Calyx of Held?
Theefore, what is the overall discovered functions of BMP signaling in the CNS?

A

BMP signaling initiates:

  1. Nerve terminal growth and synapse elimination.
  2. The maturation of presynaptic release synchronicity and postsynaptic signaling speed.

These changes together guide the development of the calyx of Held into a fast-releasing, reliable relay synapse.

Therefore, BMP signaling specifies synapse size and synapse function in the mammalian CNS

29
Q

What is the overall discovered functions of BMP signaling in the CNS?

A

BMP signaling specifies synapse size and synapse function in the mammalian CNS.

30
Q

What is the primary function of the superior olivary complex?Where is the MNTB located? How would synaptic delays here affect CNS functioning?

A

The primary function of the superior olivary complex, where the MNTB located is sound localization.
Thus delays in synaptic transmission would greatly and negatively impact auditory processing.

31
Q

JC2: Mobility of ____ is particularly important for small synapses with low channel density.
How is probability of release correlated with channel mobility?

A

Mobility of VDCCs is particularly important for small synapses with low channel density.
Pr increases with channel mobility.

32
Q

How do mobile VDCCs affect the probability of release for each individual synaptic vesicle? What is this known as?

A

Mobile VDCCs equalize the probability of release for each individual synaptic vesicle, independent from the positioning of the vesicle itself. “Plasticity-related modulation”.

33
Q

Synaptic VDCC mobility is regulated by what?

Calcium chelation has what effect on synaptic channel mobility? What chelators were used?

A

Synaptic VDCC mobility is regulated by free intracellular calcium.

Calcium chelation has negative effect on synaptic channel mobility. EGTA (slow chelation) and BAPTA (fast chelation).

34
Q

How is channel mobility affected by the numbers of channels within the pre-synaptic membrane?

Calcium channel mobility within presynaptic membranes?

A

Channel mobility is unaffected by the numbers of channels within the pre-synaptic membrane.

Calcium channels display confined mobility within presynaptic membranes. Despite the need for tight channel-sensor coupling, a large population of channels (~60%) is dynamic but confined within presynaptic membranes

35
Q

How did expression of tagged voltage-dependentcalcium channels affect the synapses?

What example of coupling is a key factor that determines the timing and efficiency of transmitter release?

A

Expression of tagged VDCCs preserved the normal synaptic phenotypes.

The coupling between VDCCs (voltage-dependent calcium channels) and calcium sensors of exocytosis on synaptic vesicles is a key factor that determines the timing and efficiency of transmitter release.

36
Q

What two major techniques were used in JC 2?

A

Single-Particle Tracking Photo-activated Localization Microscopy (sptPALM) for studying the mobility of the VDCCs.
Stimulated emission depletion microscopy (STED) to determine the expression of RIM and Bassoon clusters in presynaptic axon. Bassoon and RIM clusters became enlarged to define an area of confinement for synaptic calcium channels to keep their density and mobility largely constant.

37
Q

In the absence of BMP, how were the MNTB neurons innervated?
How KO affect timing at the Calyx of BMP1a/1b cDKO mice?

A

In the absence of BMP, MNTB neurons are innervated by several synaptic terminals; this is evidence for the persistence of multiple innervations.

The KO decreased the timing at the Calyx of BMP1a/1b cDKO mice.

38
Q

Dale’s law?

What is is responsible for up to 2/3 of a neuron’s energy expenditure (1/5 for animal cells)?

A

Dale’s law: Each nerve terminal releases a single type of transmitter.

The Na/K ATPase.

39
Q

What is the f(x) of the Na/K ATPase?

2 natural Inhibitors of it are?

A

Pumping more Na out than K in, it generates an outward current.
Natural Inhibitors: Oubain and Digoxin

40
Q

Comparing neuron to a battery, which components are equivalent to the following: Capacitor= ? Resistor = ?
Battery = ?
Potential to generate current - ?

A

Capacitor = Membrane capacitance, Capacitative current. Resistor = Membrane resistance, Leak channels.
Battery = Membrane potential.
Potential to generate current - Membrane time constant.

41
Q

What is the equation for the time constant? Equation for membrane current?

A

Time Constant: Tau = R * Cm .

Membrane current = Ic + Iionic.
Voltage lags current flow

42
Q

What is equ for Ohm’s law? What is the equation for Ix?

Identify what all the constants mean.

A

Change in V = IR = 1/G.
Ix = G * (V m - E x )
I: current, G: conductance, Vm: membrane potential, Ex: reversal potential, (Vm – Ex) is driving force.

43
Q

What determines membrane potential?

Ionic current is determined by what three factors?

A

Ionic movement across membrane determines membrane potential.

Ionic current is determined by three factors: 1) Permeability (channel opening, conductance) 2) Concentration gradient of the ion 3) Electrical potential across membrane

44
Q

What are responsible for repolarizing the membrane potential?

A

“Leak” Channels Repolarize the Membrane Potential.

45
Q

What kind of K + current at calyx of Held?
KCNQ channels mediate what?
KCNQ blockers and openers?

A

A non‐inactivating K + current at calyx of Held.
KCNQ channels mediate the presynaptic outward current.
KCNQ blockers: XE991, linopirdine.
KCNQ openers: flupirtine, retigabine.

46
Q
Locations/functions of:
KCNQ1: ?
KCNQ2/3: ?
KCNQ4: ?
KCNQ5: ?
A

KCNQ1: Non‐neuron tissues; heart disease.
KCNQ2/3: Brain, form the native M‐current; epilepsy.
KCNQ4: Cochlear hair cell and brain; deafness.
KCNQ5: In the calyx of Held.

47
Q

Diclofenac ___ KCNQ2‐KCNQ4, but ___ KCNQ5.
UCL2077 ____ KCNQ1‐4, but ____ KCNQ5.
Presynaptic KCNQ5 current activates at what voltages?
KCNQ5 helps to do what?

A

Diclofenac activates KCNQ2‐KCNQ4, but inhibits KCNQ5. UCL2077 inhibits KCNQ1‐4, but potentiates KCNQ5.
Presynaptic KCNQ5 current activates at hyperpolarized voltages.
KCNQ5 helps set presynaptic resting potential and resting conductance.