Neurobio Midterm 2

Front 1

Long-term potentiation (LTP)

Back 1

Anincrease in the size of the EPSP that is sustained for at least severalminutes.

-Strengthensthe synapse, since it makes the presynaptic cell morelikely tomake the postsynaptic cell fire.

-Possiblysustained for months or years.

Front 2

Long-term depression (LTD)

Back 2

Adecrease in the size of the EPSP that is sustained for at least severalminutes.

-Weakensthe synapse, since it makes the presynaptic cell lesslikely tomake the postsynaptic cell fire.

-Possiblysustained for months or years.

Front 3

What determines whether you get LTP orLTD?

Back 3

slowpatterns of presynaptic stimulation (1Hz or so) will cause depression, and fastpatterns of presynaptic stimulation (100Hz or so) will cause potentiation.

Front 4

site of LTP and LTD

Back 4

Hippocampus:Brain area involved in the formation and retrieval of episodic memory (memoryof autobiographical events)

Front 5

Summary of observations about hippocampalLTP

Back 5

-Highfrequency stimulation induces LTP at the hippocampal Schaffer collateral-CA1synapse.

-ThisLTP demonstrates specificity.

-ThisLTP seems to be Hebbian innature:

--Bypairing postsynaptic depolarization with a weak presynaptic stimulus, you cancreate LTP.

-ThisLTP demonstrates associativity:

--Weaksynapses coincident with strong synapse will demonstrate LTP.

Front 6

molecules involved in LTP

Back 6

-Thepresynaptic terminal releases glutamate.

-Thepostsynaptic terminal has AMPA and NMDA receptors.

Front 7

The role of the NMDA receptor

Back 7

-Therole of the NMDA receptor is central.

--Blockersof NMDARs do not affect baseline transmission but do prevent LTP.

--Micelacking NMDARs have defective plasticity in many brain areas and cannot do manytypes of learning.

-TheNMDAR only opens when there is both postsynaptic depolarization and glutamate.

--It isa “coincidence detector.”

Front 8

The role of calcium

Back 8

-Whenthe NMDAR opens, calcium comes into the terminal.

-Thiscalcium is crucial for LTP:

--Calciumchelators block LTP.

--Injectingcalcium potentiates transmission.

-Calciumactivates the kinases α-CaMKII andprotein kinase C (PKC).

Front 9

CaMKII

Back 9

-CaMKII isthe most abundant postsynaptic protein at Schaffer collateral synapses.

-Onlyexpressed in forebrain (cortex and hippocampus) of mammals.

-Pharmacologicalinhibition or genetic deletion of it prevents LTP.

-Ableto auto-phosphorylate and therefore stimulate its own activity.

--Thisability to stay active for a long time contributes to the maintenance of LTP.

-Persistenceof CaMKIIactivity is due to autophosphorylation.

Front 10

Addition of AMPARs to the membrane

Back 10

-α-CaMKII andprotein kinase C phosphorylate targets to cause insertionof more AMPARs into the membrane.

Front 11

Summary: Hippocampal LTP

Back 11

-NMDARsopen.

-Ca2+ comes in.

-CaMKII andPKC are activated.

-CaMKIIauto-phosphorylation makes activation persistent.

-Substratesare phosphorylated.

-AMPARsare inserted.

Front 12

End result of LTP

Back 12

Increase in synaptic strength

Front 13

Schaffer collateral LTD

Back 13

-Youget LTD at the Schaffer collateral synapse by using prolonged, low-frequencystimulation (1Hz vs. 100Hz).

-LTDis associated with the loss ofAMPARs.

-Insteadof kinases, LTD relies on calcium-dependent phosphatases:

--Phosphataseinhibitors affect only LTD, not LTP

-Phosphataseswould de-phosphorylate what the kinases have phosphorylated

Front 14

Schaffer collateral LTD and the NMDAR

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-Schaffercollateral LTD also requires NMDAR activation and entry of calcium.

-Whetheryou get LTP or LTD depends on the amount of calcium influx.

--Largeand fast influx -> LTP

--Slowand small influx -> LTD

Front 15

}Whydoes it “make sense” that a large amount of Ca2+ influx causes LTP, while a smallamount of Ca2+ influx causes LTD?

Back 15

-Alarge amount of Ca2+influx implies that the NMDAR is open for a long time, implying the presynapticand postsynaptic cell persistently fire together.

-Onthe other hand, a small amount of Ca2+influx may imply that the presynaptic and postsynaptic cell fire randomly withrespect to each other.

Front 16

Another site of LTD

Back 16

Cerebellum:Involved in motor control and responsible for several types of motor learning.

Front 17

Cerebellar LTD

Back 17

-LTDat this synapse only occurs when the climbing fibers (CF) and parallel fibers(PF) are activated at the same time

1.Climbing fiber input depolarizes the dendritic membrane

2.This makes voltage-gated calcium channels near the parallelfiber terminal open, letting in calcium

3.Release of glutamate from the parallel fiber stimulates AMPARs and mGluRs.

4A.Binding to AMPARs induces depolarization.

4B.Binding to mGluRsactivates phospholipase C, which eventually causes:

4Bi:The formation of DAG

4Bii:Formation of IP3

5. IP3 and the Ca2+ let in by the climbing fiberdepolarization together bind to receptors on the endoplasmic reticulum.

6.The receptors release more Ca2+ fromthe ER.

7.DAG and calcium activate PKC.

8.PKC phosphorylatessubstrates that cause the removal of AMPARs from the membrane.

Front 18

Comparisons:

Back 18

-Inboth Schaffer collateral LTD and cerebellar LTD, LTD is a result of the removalof AMPARs

--However,one uses a phosphatase and the other a kinase.

-Coincidencedetection in Schaffer collateral LTP relies on the NMDAR; coincidence detectionin cerebellar LTD relies on PKC and the IP3receptors on the ER.

Front 19

Anterograde amnesia

Back 19

Aninability to establish new memories.

Front 20

Retrograde amnesia

Back 20

Difficultyretrieving memories that have already formed.

Front 21

Declarative memory

Back 21

-storageand retrieval of information that is available to consciousness and can (atleast in principle) by expressed by language.

-}(referredto as explicitmemory) isone of two types of long-term human memory. Declarative memory refers tomemories which can be consciously recalled such as facts and knowledge.

Front 22

Non-declarative

Back 22

-Notavailable to consciousness, and difficult to express in language.

-aka procedural memory, refers to unconscious memoriessuch as skills (e.g. learning to ride a bicycle).

-divided into episodic and semantic memory

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episodic memory

Back 23

stores specific personal experiences

Front 24

semantic memory

Back 24

stores factual information.

Front 25

Immediate memory

Back 25

theability to hold ongoing experiences in mind for a fraction of a second.

-Eachsensory modality seems to have its own “register.”

Front 26

Working memory

Back 26

Abilityto hold onto information for seconds to minutes.

-Example:When you search for a specific object in a field of objects, you need toremember where you’ve already searched.

-Example:Remember a string of digits and repeat it back.

Front 27

Long-term memory

Back 27

-Daysto years.

-Forsomething to enter long-term memory, it must first enter immediate and thenworking memory. Otherwise, it will be forgotten

Front 28

EYE (gross anatomy)

Back 28

-Pupil

-Iris (thecolor of eye, regulates size of pupil)

-Cornea (clearsheet in front of the pupil and iris, most sensitive part of body)

-Sclera(thewhite of the eye, the majority of eyeball)

-Conjunctiva(insideof eyelid)

-Extraoculareye muscles

-Opticnerve

Front 29

Looking at Retina

Back 29

-Fovea (center of retina)

-Macula(site of central vision)

-Opticdisk (blind spot, head of optic nerve)

-Nasalretina

-Temporalretina

Front 30

Photoreceptors

Back 30

detectphotons in their outer segments

Front 31

Rods

Back 31

verysensitive

-Canbe responsive to one photon (used during dim light)

-Rodsare more sensitive at low light levels, but their responses saturate.

Front 32

Cones

Back 32

lesssensitive; respondto particular wavelengths of light (used during day light condition)

-Conesare less sensitive to light but do not saturate.

-Conesare associated with high-acuity vision (vision that can be used to distinguishfine details).

Front 33

Bipolar Cells

Back 33

-receiveinput from the photoreceptors and combine it.

-Havegraded potentials.

-Off-centerbipolars:express AMPARs and kainatereceptors and are excited (depolarized) by glutamate.

--depolarize to dark spots

-On-centerbipolars:express mGluRs andare inhibited (hyperpolarized) by glutamate.

--depolarize spots of light

Front 34

Path of RGC axons leaving the retina

Back 34

-TheRGC axons exit the eye and begin the opticnerve.

-Atthe opticchiasm,some axons cross to the other side.

--Crossingis called a decussation.

-Afterthe chiasm, it is now called the optictract.

* Thenasal fibers from both retinas crossover at the optic chiasm.

Front 35

Pathway to V1

Back 35

-dLGNaxons go to primaryvisual cortex (striate cortex, V1)

-Connectionfrom dLGN tocortex is called the optic radiation.

Front 36

Horizontal Cells

Back 36

-inhibitory(hyperpolarizing) cells.

-Theyreceive input from many photoreceptors (surround) butonly send inhibitory output onto a few (center).

-They are connected by gap junctions, sotheir activity reflects the overall light level in a broad area.

Front 37

Horizontal Cells: when the center is light but the surround is dark

Back 37

-whenthe center is light but the surround is dark:

--Thecenter cone is hyperpolarized.

--Releasesless glutamate.

--Thesurround cones are depolarized and release more glutamate.

--Horizontalcells are excited, so they hyperpolarize the cones.

-The center cone becomes morehyperpolarized, so it continues to not release glutamate.

-This reinforces theeffects of the light on the center cone

Front 38

Horizontal Cells: Whenboth center and surround are light

Back 38

--Thecenter cone is hyperpolarized.

--Releasesless glutamate.

--Thesurround cones are hyperpolarized and release less glutamate.

--Horizontalcells are not excited, so they do not hyperpolarize all the cones.

-The center cone becomes lesshyperpolarized, so it releases more glutamate.

--This opposes theeffect of the light on the center cone.