Neurobiology: Exam 4

Front 1

habituation (L2)

Back 1

decrease in synaptic strength due to a decreased amount of Ca2+ release and thus, less NT release (an animal learns to ignore stimuli that are neither harmful or beneficial)

a homosynaptic process and the simplest form of implicit learning

Front 2

how many training sessions leads to short term memory habituation in Aplysia?

long term? (L2)

Back 2

short: a single session of 10 stimuli. Can last for hours

long: 4+ sessions. Can last up to 3 weeks

Front 3

principle of learning (L2)

Back 3

spaced training is almost always more effective than massed training

Front 4

homosynaptic (L2)

Back 4

homosynaptic events occur at a single synapse or group of synapses, but do not involve interactions between synapses or groups of synapses.

For example, in Aplysia, decrease in synaptic strength is a direct result of activity in the sensory neurons and their central connections in the reflex pathway.

Front 5

sensitization (L2)

Back 5

involves an enhancement of synaptic transmission

causes an animal to pay attention to a variety of stimuli, even harmless ones, because the stimuli are potentially accompanied by painful or dangerous consequences

a heterosynaptic process

Front 6

heterosynaptic (L2)

Back 6

when enhancement of synaptic strength is induced by modulatory interneurons

In Aplysia, these interneurons are activated by stimulation of the tail

Front 7

experiment with Aplysia showing sensitization (L2)

Back 7

When a noxious stimulus is applied to the tail, it activates sensory neurons in the tail that excite facilitating interneurons, which form axo-axonic synapses on the terminals of sensory neurons innervating the siphon. At these synapses, the facilitating interneurons ENHANCE transmitter release from the sensory neurons, which is called PRESYNAPTIC FACILITATION. The sensory neurons can also act on motor neurons (as are in the gill)

Front 8

synaptic placicity (L2)

Back 8

each synapse can either be depressed or enhanced

Front 9

what happens in short-term sensitization (L2)

Back 9

Presynaptic facilitation by axo-axonic synapses occurs on facilitating interneurons.

These interneurons are thought to be serotonergic.

Front 10

serotonergic neurons (L2 and fig. 63-3B)

Back 10

involved in short-term sensitization

These neurons release serotonin, which binds to metabotropic receptors in the presynaptic membrane of the sensory neuron and activate a G-protein, which increases activity of adenylyl cyclase. Adenylyl cyclase produces cAMP, which activates PKA. Once activated, PKA phosphorylates serotonin-sensitive potassium channels or a protein associated with them.

Front 11

in serotonergic neurons, what are the 3 things that PKA can do? (L2)

Back 11

1. can cause phosphorylation of serotonin-sensitive potassium channels, inactivating the potassium channels, causing less potassium current, which prolongs the AP and thereby causes more Ca2+ channels to be activated and more Ca2+ influx. Thus, greater NT release.

2. can enhance the mobilization of vesicles-->they are transported to the active zone

3. can act on L-type Ca2+ channels

Front 12

What are the two second messenger pathways serotonergic neurons can work through? (L2)

Back 12

1. cAMP, PKA

2. PLC, which stimulates intramembranous DAG to activate PKC and cause proteins to be phosphorylated.

Front 13

in serotonergic neurons, what results from the PLC pathway? (fig. 63-3B)

Back 13

PLC leads to the formation of DAG, which activates PKC, which, together with PKA, causes increased vesicle mobilization/release and activation of L-type Ca2+ channels.

Front 14

L-type Ca2+ channels

N-type Ca2+ channels (L2)

Back 14

L-type: high voltage activated; long lasting

N-type: also high voltage activated. Neural type.

Front 15

2 types of memory (L1)

Back 15

1. implicit (AKA nondeclarative, unconscious): eg, reflex and perception

2. explicit (AKA declarative, conscious): eg, cognition, events, facts

Front 16

habituation in Aplysia (fig 63-1)

Back 16

A tactile stimulus to the siphon initially elicits the gill-withdrawal reflex, but repeated stimuli lead to habituation.

Initially, stimulation of the siphon will interact with excitatory and/or inhibitory interneurons, but after repeated exposure, there is a decrease in synaptic transmission between the sensory neuron and interneurons as well as between the sensory neuron and the motor neuron.

Front 17

can habituation and sensitization occur on the same synapses? (L2)

Back 17

Yes; the same synapses can be regulated in opposite ways by opposing forms of learning

Front 18

compare and contrast ST and LT sensitization: changing synapse strength (L3)

Back 18

Both ST and LT sensitization involve changes in the strength of connections at several synaptic sites, including synaptic connections between sensory and motor neurons.

The increase in synaptic strength between sensory and motor neurons in both cases is due to enhanced release of neurotransmitter (glutamate)

Front 19

compare and contrast ST and LT sensitization: NT release and facilitation (L3)

Back 19

The same neurotransmitter (serotonin) released by stimulation of the tail produces ST facilitation (after single exposure) and LT facilitation (after 5+ exposures)

Front 20

compare and contrast ST and LT sensitization: intracellular messengers (L3)

Back 20

cAMP and PKA pathways are critical for both ST and LT memory.

Front 21

compare and contrast ST and LT sensitization: protein synthesis (L3)

Back 21

LT requires synthesis of new proteins and ST doesn't.

This is illustrated using inhibitors of these proteins (eg iRNA).

Front 22

consolidation and its 3 steps (L3)

Back 22

the process by which ST memory is converted to LT memory

1. gene expression
2. new protein synthesis
3. growth or pruning of synaptic connections

Front 23

ways to de-couple ST and LT memory (1254)

Back 23

seizures, head trauma, inhibitors of protein or mRNA synthesis ALL block LT memory selectively

Front 24

Long-term sensitization of gill-withdrawal reflex in Aplysia: experimental results(fig. 63-5A)

Back 24

After the tail had been stimulated to the point of LT sensitization, the median PSP size increased and the median duration of siphon withdrawal increased as well.

Front 25

Long-term sensitization of gill-withdrawal reflex in Aplysia: the two major changes this causes in the sensory neurons of the reflex (fig. 63-5B)

Back 25

1. persistent activity of PKA
2. structural changes in the form of the growth of new synaptic connections

Front 26

second messenger pathway in serotonergic neurons (short-term to long-term sensitization) (fig. 63-5B)

Back 26

SHORT TERM
1. serotonin (released from a facilitating interneuron) acts on a postsynaptic receptor (of the sensory neuron), which activates adenylyl cyclase, which converts ATP to cAMP.
2. cAMP activates cAMP-dependent protein kinase A, which phosphorylates a number of target proteins, leading to enhanced NT availability and release.

LONG-TERM
1. If the short-term process has been occurring for a number of days, PKA recruits mitogen-activated kinase (MAPK) and together, they enter the nucleus of the sensory neuron.
2. Once in the nucleus, PKA phosphorylates the cAMP-response element binding (CREB) protein.
3. CREB proteins (transcription factors) bind to cAMP response elements (CRE) of cAMP-inducible genes.
4. To activate CREB-1, PKA removes the repressive action of CREB-2, which inhibits CREB-1. PKA does so via MAPK.
5. CREB activates a gene that encodes a ubiquitin hydrolase, which leads to proteolysis of the regulatory subunit of PKA. This results in persisten activity of PKA, leading to persistent phosphorylation of CREB-1 and MAPK (?).
6. CREB also activates a gene that encodes C/EBP (a transcription factor), which binds to the DNA response element CAAT, which activates genes that encode proteins important for growth of new synaptic connections.

Front 27

What does explicit memory in mammals involve (process in brain) (L3)

Back 27

It involves long-term potentiation in the hippocampus

Front 28

What does Alzheimer Disease affect? (L3)

Back 28

the hippocampus. Thus, long-term memory is affected.

Front 29

3 pathways for learning and memory in the hippocampus (L3)

Back 29

1. perforant fiber pathway: goes from entorhinal cortex to granule cells of dentate gyrus
2. mossy fiber pathway: contains axons of granule cells that form synapses with pyramidal cells in CA3 region of hippocampus.
3. Schaffer collateral pathway: consists of excitatory collaterals of the pyramidal cells in the CA3 region and ends on pyramidal cells in the CA1 region.

Front 30

long-term potentiation (1259)

Back 30

a brief, high-frequency train of stimuli to any of the three major synaptic pathways which increases the amplitude of EPSPs in the target hippocampal neurons.

Can last for days, minutes, years

Front 31

Long-term potentiation of the mossy fiber pathway, experiment (fig 63-8)

Back 31

METHOD
1. Stimulating electrodes are placed to as to activate two independent pathways to the CA3 pyramidal cells: the commissural pathway and the ipsilateral mossy fiber pathway.
2. Inject BAPTA (which chelates Ca2+) and fluoride into the pyramidal (post-synaptic) cell when the cell is voltage clamped. These 2 drugs block ALL second messenger pathwyas in the postsynaptic cell.

RESULTS
1. LTP in the mossy fiber pathway is unaffected, showing that it is induced presynaptically.
2. LTP in the commissural pathway is blocked because it requires activation of an NMDA receptor, meaning that this pathway is postsynaptically induced.

Front 32

what NT is released in the mossy fiber pathway and what postsynaptic receptors are involved? (1260)

Back 32

Mossy fiber terminals release glutamate, and this binds to both NMDA and non-NMDA receptors. However, these receptors play only a minor role in synaptic placicity, as evidenced by the fact that blocking them does not affect LTP.

Front 33

what does LTP in the mossy fiber pathway depend upon?

Is LTP here associative or non-associative? (1260)

Back 33

Ca2+ influx into the PRESYNAPTIC cell. This influx activates Ca2+/calmodulin-dependent adenylyl cyclase, which inreases the level of cAMP, which activates PKA and leads to greater NT release.

LTP is non-associative since it does not depend on the post-synaptic cell.

Front 34

In the mossy fiber pathway, how is LTP modulated? (1260)

Back 34

It is modulated by noradrenergic neurons, which activate beta-adrenergic receptors, which activate adenylyl cyclase.

Front 35

Schaffer collateral pathway:
what areas does it connect?
associative or non-associative?
which NT does it release?
which receptors does it employ?
(1260)

Back 35

Connects pyramidal cells of CA3 region of hippocampus with those of the CA1 region.

LTP in Schaffer collateral pathway is associative.

Its terminals release glutamate

Requires activation of NMDA receptors in the postsynaptic cell.

Front 36

associativity (1260)

Back 36

requires activity in both the presynaptic and postsynaptic cells to adequately depolarize the postsynaptic cell

Front 37

how does LTP in the Schaffer collateral pathway differ from LTP in muscle fibers? (L4)

Back 37

In Schaffer:
1. LTP requires cooperativity among afferent axons in order to remove the Mg2+ from NMDA channels and thus, activate them to conduct Ca2+.
2. LTP requires activation of the presynaptic cell (associativity).

Front 38

cooperativity (1260)

Back 38

activation of several afferent axons together

Front 39

process of LTP induction in the Schaffer collateral pathway (fig. 63-10)

Back 39

1. Once glutamate is bound to the NMDA receptors and the postsynaptic membrane is sufficiently depolarized by the action of non-NMDA receptors, the Mg2+ plug is removed from NMDA receptors, and they allow Ca2+ to flow into the postsynaptic cell.
2. The rise in intracellular Ca2+ concentration triggers Ca2+/calmodulin kinase, PKC, and a tyrosine kinase (Fyn).
3. The Ca2+/calmodulin kinase phosphorylates non-NMDA receptors, which increases their sensitivity to glutamate, which allows more of the receptors to be used. Thus, the EPSP is greater.
4. Once LTP is induced, the postsynaptic cell releases a set of retrograde messengers (NO?) to the presynaptic cell that act on protein kinases and lead to an increase in NT release by the presynaptic cell.

Front 40

In general, how are axons guided to their targets? (L5)

Back 40

In a series of discrete steps, with the help of attractive and repulsive cues in the extracellular environment.

Front 41

What is the process (5 steps) by which motor neurons are sorted? (1069)

Back 41

1. In the spinal cord, neurons are clustered into motor pools (eg. lateral and medial motor pools) and they mingle in the ventral root.
2. Axons are sorted in the plexus and then they enter different trunks; medial motor neuron axons enter the ventral trunk and lateral motor neuron axons enter the dorsal trunk at the base of the limb.
3. Axons run through large nerves within the limb, avoiding skin and cartilage.
4. Axons destined for one muscle gather together and leave the large nerves at discrete points to enter the target muscle.
5. Axons leave the intramuscular nerve to synapse on individual muscle fibers (one axon per fiber).

The time it takes for an axon to reach its target varies. Intercostal axons, for example, reach their target early because it is close.

Front 42

pioneer axons

How do they find their targets? (1069)

Back 42

the first axons to reach their targets (occurs during development)

They respond to molecular cues embedded in cells or the extracellular matrix along their way.

Front 43

example of a short-range cue and a long-range cue (L5)

Back 43

short cue: extracellular matrix. Provide precise guidance.

long cue: soluable molecules that diffuse from cell to cell. Can attract or repel axons from afar, though with less precision.

Front 44

what are 4 ways in which axons "solve the problem of long distance" when being guided to their targets? (1069)

Back 44

1. axons divide growth over a long distance into short, discrete segments (focal points) and respond to intermediate targets along the way (eg., plexus)
2. Axons navigate along gradients (eg, gradients of cell surface or soluble molecules)
3. Axons respond to positive or negative cues to find their way.
4. Axons respond to short-term or long-term cues along their way.

Front 45

The 6 steps of a (hypothetical) growth cone advancing to its target (fig. 54-7)

Back 45

1. the axon interacts with growth-promoting molecules in the extracellular matrix en route.
2. Adhesive cel surface molecules on neuroepithelial cells promote the axon's growth.
3. the axon encounters another (pioneer) axon and fasciculates with it.
4. The axon responds to a soluble chemiattractive molecule by turning toward it.
5. The axon responds to a soluble inhibitory molecule by turning away from it.
6. Finally, the growth cone contacts its target, stops elongating, and forms a terminal arbor.

Front 46

growth cone, general definition (1070)

Back 46

a sensory-motor structure that recognizes and responds to guidance cues

Front 47

3 main regions of the growth cone (1071)

Back 47

1. central core: rich in microtubules, mitochondria, and other organelles.
2. filopodia: long, slender extensions that project from the body. Contains many receptors for axon cues.
3. lamellipodia: found between the filopodia. They are motile and give the growth cone a ruffled appearance.

Front 48

Implicit vs. explicit memory (1231)

Back 48

Implicit (nondeclarative, unconscious): reflex, perception

Explicit (declarative, conscious): cognition, events, facts

Front 49

2 possible explanations for habituation, and which is correct? (L1)

Back 49

1. it results from less/more synaptic relase
2. it results from less/more NMDA receptors.

The first option is correct because the number of NMDA receptors doesn't change...just the number of vesicles decreases.

Front 50

experiment showing that cues in the extracellular matrix are critical for neurite outgrowth (L6)

Back 50

Grew neurons on substrates that were coated with molecules from the extracellular matrix.

RESULTS: found that axon outgrowth was promoted

CONCLUSIONS: indicates that the extracellular matrix is critical for outgrowth of the neuron

Front 51

proteins in the extracellular matrix that are critical for outgrowth (L6)

Back 51

laminins, collagens, fibronectin, some proteoglycans

Front 52

why is the multiplicity of laminins and integrins essential? (1074)

Back 52

The fact that there are multiple isoforms of both proteins means that they can have specific interaction and provides the potential for a great deal of subtlety in the interactions between growth cones and matrix.

Front 53

2 types of cell adhesion molecules that promote neurite outgrowth (L6)

Back 53

1. cadherins (eg, N-cadherins, bind to themselves)
2. immunoglobin-like adhesion molecules (eg, NCAMs, expressed by neurons)

Front 54

netrins, general definition (L6)

Back 54

chemoattractive molecules

glycoproteins

a family of secreted proteins that provide axon guidance.

Front 55

trophic vs. tropic factors (1079)

Back 55

trophic factors: soluble growth factors that enhace the neuron's ability to extend axons in a certain direction

tropic factors: soluble growth factor that is part of a gradient that a neuron is guided down

Front 56

which netrin molecules are important and what do they bind to? (L6)

Back 56

netrin 1 (in rats, is expressed in the ventral midline of neuronal tube) and netrin 2 are important (released from the floor plate)

They bind to receptors of the Unc5H family and DCC/neogenin family which are located on the growth cone

Front 57

How does PKA activation (phosphorylation) affect netrins? (fig. 54-13)

Back 57

under conditions of high PKA activity, growth cones are attracted to netrins. Under conditions of low PKA activity, growth cones are replled from netrins.

Front 58

ephrin (eph) kinases (L7)

Back 58

receptors (tyrosine kinases) for ephrins

found on the growth cone

once activated (by ephrin), they generate an inhibitory signal that induces growth cones in a new direction

Front 59

ephrins (L7)

Back 59

ligands found on tectal cells and distributed broadly throughout the nervous system

Front 60

semaphorins (1081)

Back 60

a ligand of which there are at least 15 known types

capable of causing growth cones to stop growing, collapse, and then grow in a new direction

expressed by the target (eg, tectum)

their receptors are neuropilins and plexins

can act as a short-range signal (when membrane-bound)

the soluble type are chemorepellants

Front 61

what does the endoderm develop into?
mesoderm?
ectoderm? (L8)

Back 61

endoderm: gut, lungs, and liver

mesoderm: connective tissue, muscles, vascular system

ectoderm: central and peripheral nervous system

Front 62

neurulation (L8)

Back 62

the process by which the neural plate begins to form the neural tube

Front 63

the caudal region of the neural tube gives rise to the ______.

the dorsal region gives rise to the ______. (L8)

Back 63

spinal cord

brain

Front 64

neural and glial cells derive from what? (L8)

Back 64

a sheet of ectoderm cells located at the dorsal midline of the embryo at the gastrula stage.

Front 65

the formation of the neural tube are controlled by 2 major groups of factors: what are they? (L8)

Back 65

1. inducing factors: signaling factors from neighboring cells that can exert their effects locally or over a long range.

2. surface receptors: molecules that are activated in cells upon exposure to inducing factors from other cells.