BIOS 286 Exam 3 -Olfaction, Plasticity, Learning & Memory

metabotropic (GPCRs are metabotropic)

are odorant receptors ionotropic or metabotropic?

g-protein coupled receptors (GPCRs, largest subfamily of them)

are odorant receptors ion channels or GPCRs?

the cilia

on what part of the ORN are odorant receptors expressed specifically?

another part of the cell

are odorant receptors densely expressed in the axonal terminal or in another part of the cell?

excitatory (glutamatergic)

are ORNs inhibitory or excitatory?

glutamate

what neurotransmitter do ORNs utilize?

yes (neurogenesis every 4-8 weeks)

do ORNs regenerate?

olfactory epithelium

where are the cell bodies of ORNs located?

cilia

thin protrusions from the dendrites of ORNs containing odorant receptors

dendrites of ORNs (mucus layer)

where are cilia located?

broad tuning curves

do odorant receptors have broad or narrow tuning curves?

receptors bind to multiple odorants/ligands (overlap of odorant expression)

what does having a broad turning curve mean in terms of ligand-to-receptor binding?

yes (mammals: human = 10cm², cat = 20cm², dog = 170cm²)

does the size of the olfactory epithelium vary amongst species?

no, variable % of pseudogenes (inactive)

are all odorant receptor genes in the human genome functional?

one gene

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

broad tuning curve (overlap of odorant expression)

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

no (only one kind)

does a single ORN express multiple kinds of odorant receptors on its cilia membrane?

receptor cilia

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

CNG and Ca2+ activated Cl- channels

opening of what types of membrane channels causes membrane depolarization (in olfactory cilia)?

adenylyl cyclase (AC)

what does the g-protein activate (what is the enzyme)?

glomeruli

where axons of olfactory receptor cells expressing the same gene meet in the olfactory bulb

yes

do the axons from olfactory receptor neurons end in the glomeruli?

ORNs expressing the same gene

do glomeruli receive input from random ORNs or from ORNs expressing the products of the same odorant receptor genes?

olfactory cortex

olfactory bulbs project to the ______ directly

olfactory tract

the olfactory bulbs project to the olfactory cortex via the…

only one

each mitral cell receives information from only one/many glomerulus

periglomerular (PG), tufted, mitral (MT), granule (GC), other interneurons

what kinds of cells lie in the olfactory bulb?

reciprocal connections

mitral and tufted cells make __________ with periglomerular and granule cells

one cell excites another cell, which in turn, inhibits the first cell

reciprocal connections are when…

laminar (layered)

olfactory bulbs have a _______ structure

mitral cells and tufted cells

which are the only cells which project out of olfactory bulbs and into the primary olfactory cortex?

granule cells & periglomerular cells

which are some main inhibitory cells that are thought to mediate lateral inhibition in the olfactory bulbs?

granule cells

inhibitory cells (that release GABA) in the olfactory bulb and make reciprocal connections with mitral cells

lateral inhibition

what phenomenon seen in sensory systems are granule cells thought to mediate in the olfactory bulbs?

signal discrimination / contrast enhancement

lateral inhibition is…

yes

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

(odor fatigue/adaptation) pathway one

• Ca2+ entry via activated CNG channels

• Ca2+ binds Ca2+ binding protein (calmodulin)

• Ca2+ calmodulin/protein complex modulates CNG channel, reduces cAMP affinity

• decreased olfactory transduction

(odor fatigue/adaptation) pathway two

• Ca2+ entry via activated CNG channels

• Ca2+ activated CaMK II (Ca2+/calmodulin-dependent protein kinase II)

• CaMK II reduces Adenylyl cyclase (AC) activity via AC phosphorylation

• less cAMP produced

• decreased olfactory transduction

primary olfactory cortices: piriform cortex, amygdala, entorhinal cortex,& olfactory tubercle

what brain areas do bulbar projection neurons directly send their axons to (what are their direct targets)?

no

does olfactory information require thalamic relay (going to thalamus before primary olfactory cortex) just like every other sensory modality?

• secondary olfactory cortices: insula (area of proposed flavor reception), orbitofrontal cortex (OFC)

• hippocampus (object association), thalamus

• hypothalamus

secondary/indirect targets of bulbar projection neurons

where Schaffer collaterals (axons of CA3 pyramidal neurons) synapse onto CA1 pyramidal neurons

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

axons/processes from CA3 pyramidal neurons

what are Schaffer collaterals?

yes

are CA3 neurons glutamatergic (excitatory synapses)?

AMPA and NMDA receptors

what postsynaptic receptors mediate plasticity?

NMDARs - AMPA receptors must allow enough Na+ in to repel the Mg2+ blocking the NMDA receptor (from allowing Na+ and Ca2+ in for further depolarization)

which postsynaptic receptors are considered coincidence receptors and why?

Ca2+

what is the ion of importance that NMDA/coincidence receptors are permeable to which participates in signaling intracellular pathways?

yes

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

yes (less Ca2+ influx = LTD, more = LTP)

does activity of NMDARs correlate with levels of intracellular calcium?

both

is calcium signaling important for LTP, LTD, or both?

protein phosphatases

small increases in intracellular Ca2+ activate…

protein kinases

large increases in intracellular calcium activate…

both

when glutamate is released presynaptically by the axons of CA3 neurons and diffuses down the cleft to the postsynaptic membrane, does it bind both AMPARs and NMDARs or only one of those?

no

do NMDARs open as soon as glutamate binds?

Mg2+ blocks pore

why don’t NMDARs open as soon as glutamate binds?

AMPARs to allow enough Na+ influx to repel Mg2+ block

what do NMDARs require in order to open?

NMDARs

what receptors have to be activated/opened in order for LTP to take place?

post-synaptically

are NMDA receptors expressed pre- or post-synaptically at the CA3 to CA 1 synapse?

ligand-gated ion channels

what kind of receptors are AMPA and NMDA receptors in the first place?

no

are AMPARs and NMDARs GPCRs?

yes

are AMPARs and NMDARs ionotropic receptors?

yes

are AMPARs and NMDARs ligand-gated ion channels?

no (NMDARs are voltage-dependent but do not require voltage to open)

are AMPARs and NMDARs voltage-gated ion channels?

Mg2+ expulsion from NMDARs, Ca2+ influx (depolarization), increase in activity

what postsynaptic changes lead to a potentiated postsynaptic response?

yes

Does the phosphorylation of existing and the addition of new AMPARs both lead to a higher postsynaptic depolarization in response to presynaptic glutamate release?

yes

Is higher postsynaptic depolarization mediated by the calcium-dependent activation of certain kinases (enzymes)?

yes

Can structural changes also potentiate the postsynaptic response?

formation of additional postsynaptic sites (dendritic spine morphogenesis) and growth of postsynapse sites

how can structural changes potentiate the postsynaptic response?

dendritic spine morphogenesis

activity dependent formation, growth and maturation of new spines→ increased connectivity between axon and dendrites→ more contacts, larger overall contact area→ increased probability for synaptic release

yes (through phosphorylation)

can we grow existing synapses?

yes

can we grow new synapses between two cells?

only synapses receiving strong inputs and not all synaptic connections will be strengthened

what does input specificity mean in the context of LTP?

only synapses receiving a prolonged low-intensity stimulus input will be depressed/weakened

what does input specificity mean in the context of LTD?

dependent on local activity

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

is plasticity in the hippocampus dependent on intracellular calcium signaling in the postsynaptic neuron?

yes - protein kinases

does calcium activate a specific set of enzymes in LTP?

phosphorylate AMPARs (leading to increased activity)

what do protein kinases do in order to potentiate the post-synaptic response?

protein phosphatases

What enzymes are activated by calcium in LTD?

HFS —> high Ca2+ influx —> [Ca2+] > 5 micromolar —> protein kinase —> phosphorylated synaptic protein yields LTP

LTP pathway

LFS —> [Ca2+] 1 micromolar —> protein phosphatase —> unphosphorylated protein yields LTD

LTD pathway

• insertion of more AMPARs into the post-synaptic membrane

• does not require new protein synthesis

• short-lasting - one to a few hours

what are the events that happen in the postsynaptic dendritic spine during early LTP?

synthesis of new proteins/RNA

what is the one event only associated with late LTP and not early?

• submerged platform (morris maze) = mutants slower in finding… don’t learn shape-location associations

• mazes + food = never learn correct direction of food’s location, always guessing

are there any experiments (ephys or behavior) in mice that show the importance of NMDARs in the conduction and maintenance of LTP in the hippocampus?

habituation

decrease in the strength of a behavioral response to a repeated application of a mild stimulus

• organism/circuit learns to ignore stimuli that are no longer novel to free ability to respond to novel/important stimuli

decrease

is habituation an increase/decrease of a response with repetitive stimulation?

non-associative learning

is habituation a form of conditioning or non-associative learning?

repeated touching of siphon = decreased gill retraction

habituation in aplysia

motor neuron

does the activity in the sensory or the motor neuron change in order for the gill withdrawal behavior to be observed?

decreased neuronal activity

how does the activity of motor neurons change in habituating aplysia?

medial temporal lobe

We learned from the case of H.M. that structures in what lobe are very important for the formation of declarative memories?

no

Are those structures also vital for the formation and retention of motor/procedural memories based on studying patient H.M.?

anterograde amnesia (unable to form new memories / retain new info)

What were H.M.’s most severe symptoms after the surgery?

cannot form new declarative memories

Was H.M. incapable of forming new declarative memories or new procedural/motor memories, or recalling previously learned skills?

improve (stopped)

Did the seizures improve or did they get worse?

b. an increase in synaptic strength will occur only at synapses receiving strong inputs and not at other synapses that are not receiving strong inputs

What does “input specificity” refer to in the context of LTP in hippocampus?

a. an increase in synaptic strength will occur at all synapses including the ones which do not receive strong inputs (such as high-frequency stimulation) as long as they are on the same cell as the ones receiving strong inputs

b. an increase in synaptic strength will occur only at synapses receiving strong inputs and not at other synapses that are not receiving strong inputs

c. input specificity means that LTP is specific to a single brain area

d. input specificity means that LTP is specific to inhibitory synapses only

e. input specificity means that if some synapses a cell makes strengthen, other synapses that cell makes have to weaken regardless of activity

a. insertion of additional AMPA receptors into the plasma membrane

During hippocampal LTP, increased postsynaptic responses in the CA1 neuron can result from:

a. insertion of additional AMPA receptors into the plasma membrane

b. dephosphorylation of existing membrane AMPA receptors

c. decreases in intracellular calcium

d. activation of voltage-gated potassium channels

e. decreased activity of NMDA receptors

e. none of the above: all the above events are associated with early phase LTP

What event is NOT associated with the early phase of LTP?

a. phosphorylation of existing AMPA receptors

b. insertion of more AMPA receptors into the membrane

c. increases in intracellular calcium concentrations

d. activation of protein kinases

e. none of the above: all the above events are associated with early phase LTP

e. none of the above – the best area to apply the odorant is not listed

If you wanted to evoke a response in an olfactory receptor neuron, the best area on the neuron to apply the odorant will be:

a. the base of the soma

b. along the length of the axon

c. at the axonal terminal

d. b and c

e. none of the above – the best area to apply the odorant is not listed

c. any one given olfactory receptor neuron expresses the products (proteins) of multiple odorant receptor genes

Which of the following statements about the olfactory system is INCORRECT?

a. the size of the olfactory epithelium varies amongst species

b. the number of total odorant receptor genes in the human (and other mammals) genome is higher than that of functional receptor genes because some are pseudogenes

c. any one given olfactory receptor neuron expresses the products (proteins) of multiple odorant receptor genes

d. olfactory receptor genes encode for G-protein-coupled receptors

e. pseudogenes do not produce the expression of functional odorant receptors

b. postsynaptic cytosolic calcium increases correlate with activity of postsynaptic NMDA receptors

Which of the following statements about synaptic plasticity in the hippocampus is correct?

a. changes in synaptic strength are dependent only on AMPA receptors

b. postsynaptic cytosolic calcium increases correlate with activity of postsynaptic NMDA receptors

c. activation of protein kinases is independent of calcium levels in the postsynapse

d. activation of protein phosphatases requires very high levels of cytosolic calcium

e. a and d