exam 3 Flashcards

(43 cards)

1
Q

What are odorant receptors (e.g., ionotropic vs metabotropic receptors or ion channels or
GPCRs?

A

Odorant receptors are G-protein-coupled receptors (GPCRs), not ionotropic receptors.
They do not form ion channels themselves but initiate a metabotropic cascade leading to ion channel opening.

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2
Q

Where are odorant receptors expressed specifically?

On what part of the ORN? For example, are they
densely expressed in the axonal terminals or in another part of the cell?

A

They are densely expressed on the cilia of ORNs.

The cilia project from dendritic knobs at the apical end of the ORNs, facing the nasal cavity.
Not expressed on axonal terminals.

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3
Q

Are ORNs inhibitory or excitatory? What NT do they utilize?

A

ORNs are excitatory and use glutamate as their primary neurotransmitter.

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4
Q

Do ORNs regenerate?

Where are the cell bodies of ORNs located?

A

Yes! ORNs regenerate throughout life, approximately every 30–60 days.

2ND: In the olfactory epithelium, a specialized region in the nasal cavity.

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5
Q

Do odorant receptors have broad or narrow tuning curves?

What does it mean
in terms of ligand to receptor binding?

A

Odorant receptors have broad tuning curves,

A single receptor can bind multiple odorants (with varying affinities).

A single odorant can bind multiple receptors. This leads to a combinatorial code for odor detection.

2ND: Broad tuning means:

Low specificity but high sensitivity to a range of similar molecules

Each odorant activates a combinatorial pattern of receptors → This pattern is decoded by the brain to identify the odor

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6
Q

Does the size of the olfactory epithelium
vary amongst species?

A

Yes!

In species with a strong sense of smell (e.g., dogs), the epithelium is larger and more densely packed with ORNs.

In humans, it’s relatively small.

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7
Q

Each olfactory receptor neuron expresses the products
(proteins) of how many odorant receptor genes?

Why can a single ORN be activated/depolarized by
multiple odorant molecules?

Does it express multiple
kinds of odorant receptors on its cilia membrane?

A

1ST: Only ONE functional odorant receptor gene is expressed per ORN

2ND: Because the receptor it expresses has a broad tuning curve.
However, each ORN expresses only one receptor type on its cilia.

3RD: However, each ORN expresses only one receptor type on its cilia.

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8
Q

On what part of the neuron should I apply an odorant if
I wanted to stimulate that neuron in a laboratory under
experimental conditions?

A

Apply odorants to the cilia (on the apical surface of the ORN).
That’s where receptors and signal transduction machinery are localized.

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9
Q

Are all odorant receptor genes in the
human genome functional?

A

No.

Humans have ~400 functional odorant receptor genes.

But also ~600 pseudogenes (nonfunctional due to mutations).

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10
Q

Olfactory signal transduction in the cilia:

opening of what types of membrane
channels causes membrane
depolarization?

What does the G protein activate (what is
the enzyme)?

A

1/2: Odorant binds → GPCR (odorant receptor)

G protein (Golf) activates adenylyl cyclase

cAMP is produced → opens cyclic nucleotide-gated (CNG) channels

Na⁺ and Ca²⁺ influx → depolarization

Ca²⁺ also activates Cl⁻ channels, causing Cl⁻ efflux, further depolarizing the cell

3RD: The G protein (Golf) activates adenylyl cyclase III (AC3) → increases cAMP.

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11
Q

Olfactory bulbs:

what are glomeruli?

Do the axons from olf. receptor neurons end in the glomeruli?

Do glomeruli receive input from RANDOM ORNs or from ORNs expressing the
products of the SAME odorant receptor genes?

A

Glomeruli are spherical structures in the olfactory bulb where:

Axons of ORNs (that express the same receptor gene) converge

They synapse onto mitral and tufted cells

3RD: Each glomerulus receives input from only one type of odorant receptor (not random).

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12
Q

how complex are olfactory bulbs

A

Yes—very complex:

Multiple cell layers: glomerular layer, external plexiform layer, mitral cell layer, granule cell layer

Many cell types: mitral cells, tufted cells, periglomerular cells, granule cells

Contains both excitatory and inhibitory circuits

DO not forget that olfactory bulbs
project to olf. cortex directly via the olfactory tract!

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13
Q

Which are the only cells which project out of the bulbs and into primary olf. cortex (2 cell
types)?

Which are some main inhibitory cells that are thought to mediate lateral inhibition in
bulbs?

A

Mitral cells

Tufted cells
→ These are the main projection neurons of the bulb. They send axons via the olfactory tract to the primary olfactory cortex.

2ND: Periglomerular cells: Inhibit mitral/tufted cells within glomeruli.

Granule cells: Inhibit mitral/tufted cells via dendrodendritic synapses in deeper layers (external plexiform layer).

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14
Q

What are granule cells? Why did we say they are important?

What phenomenon seen in sensory systems are they thought to mediate in the olf. bulbs?

A

They are axless GABAergic interneurons.

They mediate dendrodendritic inhibition onto mitral cells.

2ND: Functionally, they are thought to contribute to:

Lateral inhibition (sharpening odor representations)

Pattern separation

Odor discrimination

Olfactory learning & memory

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15
Q

Is olfactory adaptation calcium-mediated (is calcium required for both proposed intracellular pathways of adaptation)?

What are the two proposed signaling pathways that ultimately lead to a reduced response to the odorant? (Hint: Ca2+
mediated reduction of CNG channel activity and/or Ca2+ mediated recuction of AC activity).

A

Yes—both proposed intracellular pathways for adaptation require Ca²⁺.

2ND: Ca²⁺ → binds calmodulin → inhibits CNG channels → ↓ Na⁺/Ca²⁺ influx → ↓ depolarization

Ca²⁺ → activates calmodulin → inhibits adenylyl cyclase (ACIII) → ↓ cAMP → ↓ CNG channel opening

→ Net effect: reduced sensitivity to sustained odorants (adaptation).

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16
Q

What are the direct targets of the bulbar projection neurons (meaning, what brain areas do the projection neurons of the
bulbs send their axons to?

A

Piriform cortex (primary olfactory cortex)

Amygdala

Entorhinal cortex

Olfactory tubercle

These areas mediate odor perception, emotion, and memory.

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17
Q

Does olfactory information require thalamic relay just like every other sensory modality (meaning
does the information from the bulbs have to go first to thalamus before it goes to primary olfactory cortex)?

A

No. Olfactory information is unique:
→ It bypasses the thalamus and goes directly to primary olfactory cortex.
(Thalamus is involved later in higher-order olfactory processing, not initial relay.)

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18
Q

Where exactly is plasticity
heavily studied in hippocampus
that we discussed in class?

What synaptic region?

What are Schaffer collaterals?

Are
CA3 neurons glutamatergic?

A

1ST/2ND: In the CA1 region, particularly at synapses between CA3 and CA1 neurons.

3RD: Axons from CA3 pyramidal neurons that synapse onto CA1 pyramidal neurons.

4TH: Yes—CA3 pyramidal neurons release glutamate.

19
Q

What postsynaptic receptors mediate
plasticity?

A

AMPA receptors (AMPARs): fast excitatory response

NMDA receptors (NMDARs): critical for synaptic plasticity

20
Q

Which postsynaptic receptors
are considered coincidence sensors and
why?

A

NMDARs are coincidence detectors because they:

Require glutamate binding

And postsynaptic depolarization (to relieve Mg²⁺ block) → They only allow ion flow when both conditions are met.

21
Q

What is the ion of importance that
they are permeable to which participates
in signaling intracellular pathways?

A

Ca²⁺ (calcium): enters via NMDARs and triggers intracellular pathways

22
Q

What are NMDARs?

ARE THEY GPCRS?

A

N-methyl-D-aspartate receptors

Ligand-gated ion channels

Permeable to Na⁺, K⁺, and crucially Ca²⁺

2ND: No—they are ionotropic receptors (ligand-gated channels), not GPCRs.

23
Q

Does activity of postsynaptic
NMDARs correlate with changes in
synaptic strength in general?

A

Yes—more NMDAR activation → more Ca²⁺ influx → stronger synaptic changes (LTP/LTD).

24
Q

Does
activity of NMDARs correlate with
levels of intracellular calcium?

A

Yes—NMDAR opening is a major source of Ca²⁺ in dendritic spines.

25
Is calcium signaling important for LTP, LTD or both?
Both. Low/moderate Ca²⁺ → LTD (long-term depression) High Ca²⁺ → LTP (long-term potentiation)
26
Do NMDARs open as soon as glutamate binds? Why or why not? What do NMDARs require in order to open?
No. NMDARs require two things to open: Glutamate binding AND Postsynaptic depolarization to remove the Mg²⁺ block → The depolarization typically comes from AMPAR-mediated Na⁺ influx.
27
What receptors have to be activated/opened in order for LTP to take place? Are these receptors expressed pre-or post-synaptically at the CA3 to CA1 synapse?
AMPARs (for initial depolarization) NMDARs (to allow Ca²⁺ influx, triggering LTP signaling) 2ND: Both receptors are postsynaptic at the CA3 → CA1 synapse.
28
What kind of receptors are AMPA and NMDA receptors in the first place? Are they GPCRs? Are they ionotropic receptors? Are they ligand-gated ion channels? Are they voltage-gated ion channels?
BOTH NOT GPCRS BOTH LIGAND-GATED NMDAR IS PARTIALLY VOLTAGE GATED. AMPA IS NOT
29
What postsynaptic changes lead to a potentiated postsynaptic response (think of the 2 pathways related to AMPARs expression and activity)?
How does LTP increase postsynaptic response? Phosphorylation of existing AMPARs → ↑ open probability or conductance Insertion of new AMPARs into the membrane → Both lead to larger depolarization in response to glutamate.
30
Does phosphorylation of existing and addition of new AMPARs both lead to a higher postsynaptic depolarization in response to presynaptic glutamate release?
Yes, both: Phosphorylation of existing AMPARs Addition (insertion) of new AMPARs → Increase postsynaptic depolarization in response to glutamate released by the presynaptic neuron. How? Phosphorylation (by CaMKII, PKA, PKC, etc.) makes existing AMPARs: Open more easily Stay open longer Conduct more ions (↑ Na⁺ influx) New AMPARs increase the total number of glutamate-sensitive ion channels on the membrane → More current = stronger depolarization
31
Are these changes mediated by the calcium-dependent activation of certain kinases (enzymes)?
Yes. NMDAR-mediated Ca²⁺ influx activates: CaMKII PKC PKA → These kinases phosphorylate AMPARs and promote trafficking of new AMPARs to the membrane.
32
What does input specificity mean in the context of LTP and LTD?
Only active synapses undergo plasticity. Inactive synapses do not → LTP is input-specific, not global.
33
Is LTP dependent on local activity only at synapses at which it occurs or is LTP happening at one synapse dependent on what is happening at all other synapses the neuron makes?
Yes. LTP occurs only at the synapse where: Glutamate is released Sufficient postsynaptic depolarization occurs → Other synapses are unaffected unless they’re also active.
34
Does calcium activate a specific set of enzymes in LTP? What do these enzymes do in order to potentiate the postsynaptic response? How about the enzymes activated by calcium in LTD? Know the signaling pathways to the left.
Calcium-activated enzymes in LTP: CaMKII, PKA, PKC Their actions: Phosphorylate AMPARs Increase AMPAR insertion Initiate gene transcription (late LTP) 2ND: Protein phosphatases (e.g., PP1, calcineurin) → They dephosphorylate AMPARs → internalization → weakened response
35
What are the events that happen in the postsynaptic dentritic spine during early LTP?
Events in early LTP (E-LTP): Ca²⁺ influx via NMDAR Activation of kinases AMPAR phosphorylation and insertion
36
What is the one event I mentioned that is only associated with late LTP and not with early?
One event only associated with late LTP (L-LTP): Gene transcription and protein synthesis Required for long-term structural changes
37
Are there any experiments (ephys or behavior) in mice that I talked about in class that show the importance of NMDARs in the conduction and maintenance of LTP in hippocampus?
Experiments in mice: NMDAR knockout mice (or NMDAR antagonists) Show impaired LTP Perform poorly in spatial memory tasks (e.g., Morris water maze) → Strong evidence that NMDARs are required for LTP and learning
38
What is habituation? Is it an increase or decrease of a response with repetitive stimulation? Is this a form of conditioning or non-associative learning?
Decrease in response with repetitive stimulation It is a form of non-associative learning (not paired with another stimulus)
39
Describe habituation in Aplysia. Does the activity in the sensory or the motor neuron change in order for the gill withdrawal behavior to be observed? How does that activity change (hint: increased or decreased neuronal activity)?
With repeated touching of the siphon: ↓ neurotransmitter release from sensory neurons → ↓ activation of motor neurons → ↓ gill withdrawal reflex → The sensory neuron activity decreases.
40
We learned from the case of H.M that structures in what lobe are very important for the formation of declarative memories? Are those structures vital for the formation and retention of motor/procedural memories also based on studying patient H.M.?
Structures in the medial temporal lobe (especially hippocampus) are critical for declarative memory formation. PROCEDURAL MEMS AFFECTED? No. H.M. could still form new motor skills (e.g., mirror drawing), even though he had no memory of learning them.
41
What were H.M.’s most severe symptoms after the surgery? Was he uncapable of forming new declarative memories or new procedural/motor memories, or recall previously learned skills? Did the seizure improve or did they get worse?
Severe anterograde amnesia Could not form new declarative memories Preserved motor memory and older declarative memories Seizures greatly improved after surgery
42
Where are cilia located and what are cilia?
Cilia are long, thin projections from the dendritic knobs of ORNs. They are embedded in the mucus layer and house the odorant receptors. Cilia increase surface area for odorant detection.
43
Can structural changes also potentiate the postsynaptic response? How? Can we grow existing synapses? Can we grow new synapses between two cells?
Yes. Spine growth or new spine formation ↑ surface area = ↑ number of receptors = ↑ synaptic strength Existing synapses can grow, and new synapses can form between neurons