NBIO-160A-1

CellularandNetworkMechanismsof MemoryProfessorJohnLisman

Fall2016

Office: Volen 342A

Office hours by Appointment: CallNonna at X63148 or.

Coursematerial availableon LATTE

Prerequisites: N140

Course Grading:4 short writing assignments (5 points each); term paper (20 points); midterm (25 points); final (35 points).

The midtermand finalwillconsist ofquestionsabout figuresthat wehave discussedin class and definitions.

Goals ofthe course:Tounderstand the types ofmemory, theunderlying cellular andmolecularmechanisms,and thebrain networksinvolved.Physiologicaland behavioral methodsfor studyingmemorywill bediscussed. Studentswilllearnskills necessaryfor researchingthe literature and writingapaper in scientific style.Through inclassdiscussion ofprimarypapers, students willlearn howto readandanalyze suchpapers.

Classes on Tuesdays and Thursdays, 3:30 - 4:50 PM at Shapiro Science Center, GL-14

Course Syllabus:

1.Thursday,August 25-th

Networks with recurrent modifiable excitatory connections can store memories and perform pattern completion. The underlying process is synapse-specific Hebbian modification.

  • Kelso SR, GanongAH,Brown TH. Hebbian synapses in hippocampus.Proc NatlAcadSci US A.1986 Jul;83(14):5326-30.
  • HestrinS,NicollRA,Perkel DJ, Sah P. Analysisofexcitatorysynapticaction in pyramidalcellsusingwhole-cell recordingfrom rathippocampalslices.JPhysiol. 1990 Mar; 422:203-25.
  • Picture of hippocampalcircuitfrom me andCajal.

2.Tuesday,August 30-th

Demonstrationthat LTP in the amygdalais amechanismofmemory in classical conditioning.

  • Nabavi S, FoxR, ProulxCD,Lin JY, TsienRY,MalinowR. Engineering amemorywithLTDandLTP.Nature. 2014 Jul 17; 511(7509):348-52.doi: 10.1038/nature13294.Epub 2014 Jun 1.

3.Thursday,September 1-st

Evidence that LTP is a mechanism of episodic memory

  • Abraham WC,LoganB,Greenwood JM, DragunowM. Abraham WC,LoganB,Greenwood JM,DragunowM.Inductionandexperience-dependentconsolidation of stable long-termpotentiationlastingmonths in the hippocampus. JNeurosci. 2002 Nov 1; 22(21):9626-34.
  • WhitlockJR, Heynen AJ, Shuler MG,Bear MF.Learninginduces long-term potentiation in thehippocampus.Science. 2006 Aug25; 313(5790):1093-7.
  • BrunVH,YtterboK, Morris RG,Moser MB, Moser EI.Retrogradeamnesia for spatial memoryinducedbyNMDA receptor-mediatedlong-termpotentiation. JNeurosci. 2001 Jan 1; 21(1):356-62.
  • NakazawaK,Quirk MC,ChitwoodRA,Watanabe M, YeckelMF,SunLD,KatoA,Carr CA,Johnston D,Wilson MA,TonegawaS. Requirement for hippocampalCA3NMDA receptors inassociative memoryrecall. Science. 2002 Jul 12; 297(5579):211-8.Epub 2002 May30.
  • HillTC,ZitoK.LTP-inducedlong-termstabilization of individualnascentdendritic spines.JNeurosci. 2013 Jan 9; 33(2):678-86.doi: 10.1523/JNEUROSCI.1404-12.2013.

4.Tuesday,September 6-th

The entry ofCathroughNMDARs:role in LTPand LTD

  • NevianT,SakmannB. Spine Ca2+ signalingin spike-timing-dependentplasticity. JNeurosci.2006 Oct 25; 26(43):11001-13.
  • LismanJ,Yasuda R,Raghavachari S. Mechanisms ofCaMKIIaction in long-termpotentiation.NatRevNeurosci. 2012Feb 15; 13(3):169-82.doi: 10.1038/nrn3192.

5.Tuesday,September 13-th

Role ofCaMKII in LTP induction

  • FukunagaK,Muller D,MiyamotoE.Increasedphosphorylation of Ca2+/calmodulin-dependentproteinkinaseII and its endogenoussubstrates in the induction of long-termpotentiation.JBiolChem. 1995 Mar 17; 270(11):6119-24.
  • Lee SJ, Escobedo-Lozoya Y,SzatmariEM, YasudaR. Activation ofCaMKIIin single dendriticspinesduringlong-termpotentiation.Nature. 2009 Mar 19; 458(7236):299-304.doi:10.1038/nature07842.
  • Giese KP,FedorovNB,FilipkowskiRK, SilvaAJ. Autophosphorylation at Thr286 ofthe alphacalcium-calmodulinkinaseIIinLTPand learning.Science. 1998Feb 6; 279(5352):870-3.
  • LismanJ,SchulmanH,Cline H.The molecular basis ofCaMKIIfunction in synaptic andbehaviouralmemory.Nat RevNeurosci. 2002 Mar;3(3):175-90.

6.Thursday,September 15-th

Evidence that LTP is mediated by enhancement of AMPARs

  • Matsuzaki M, Honkura N,Ellis-DaviesGC,KasaiH.Structuralbasis of long-termpotentiation insingle dendritic spines.Nature. 2004 Jun 17; 429(6993):761-6.Epub 2004Jun 9.
  • PattersonMA,SzatmariEM,Yasuda R. AMPA receptorsareexocytosedinstimulatedspinesandadjacentdendrites in aRas-ERK-dependent mannerduringlong-term potentiation.Proc NatlAcadSci US A. 2010Sep 7; 107(36):15951-6.doi: 10.1073/pnas.0913875107.Epub 2010 Aug23
  • Liao D, Jones A, Malinow R. 1992. Direct measurement of quantal changes underlying long-term potentiation in CA1 hippocampus. Neuron 9: 1089-97

7.Tuesday,September 20-th. Led by Nick Otmakhov

How CaMKII enhances AMPAR function---CaMKIIdependent phoshphorylationofSynGapproducesearly LTP. Role ofPSD-95 in anchoringAMPAR

  • Bats C, GrocL,ChoquetD.The interactionbetweenStargazinandPSD-95regulatesAMPAreceptor surface trafficking.Neuron. 2007 Mar1; 53(5):719-34.
  • ArakiY,ZengM,Zhang M, Huganir RL. Rapid Dispersion ofSynGAP from Synaptic SpinesTriggersAMPA ReceptorInsertionand Spine Enlargement during LTP.Neuron. 2015 Jan 7;85(1):173-189.doi: 10.1016/j.neuron.2014.12.023.

8.Thursday,September 22-nd

Structuralgrowthduringlate LTP: tag and capture

  • Bosch M, CastroJ,SaneyoshiT,MatsunoH, SurM, HayashiY.StructuralandMolecularRemodelingof DendriticSpine SubstructuresduringLong-TermPotentiation.Neuron. 2014 Apr16; 82(2):444-59.doi: 10.1016/j.neuron.2014.03.021.
  • Tanaka J,Horiike Y,Matsuzaki M, MiyazakiT,Ellis-DaviesGC,KasaiH.Proteinsynthesisandneurotrophin-dependentstructural plasticityof single dendritic spines.Science. 2008 Mar 21;319(5870):1683-7.

9.Tuesday,September 27-th

Role of CaMKII in long-term memory storage

  • SanhuezaM,LismanJ.The CaMKII/NMDAR complexas a molecular memory. MolBrain. 2013Feb 14; 6:10. doi: 10.1186/1756-6606-6-10.Review.
  • Lisman JE. Refreshingmemories.Elife. 2014; 3:e02041. doi: 10.7554/eLife.02041.Epub 2014Jan 29.
  • UrakuboH,Sato M,IshiiS, Kuroda S.Invitroreconstitution ofaCaMKIImemoryswitchbyanNMDA receptor-derivedpeptide.BiophysJ. 2014 Mar 18; 106(6):1414-20.
  • Study questions for exam.

10.Thursday,September 29-th

  • Midterm:

11.Thursday,October 6-th

Place cells ofthe hippocampus(O’Keefe) and grid cells of the entorhinal cortex

  • Electrophysiologicalrecordings from thehippocampus: readingthemind ofa rat
  • Moser EI, Moser MB. 2013. Grid cells and neural coding in high-end cortices. Neuron 80: 765-74

12.Tuesday,October 11-th

Oscillations and the neural code; definition of a neural ensemble; predicting upcoming events (phase precession)

  • LismanJ,BuzsákiG. Aneural codingschemeformed bythecombined function of gamma andtheta oscillations.Schizophr Bull. 2008 Sep;34(5):974-80.doi: 10.1093/schbul/sbn060.Epub 2008Jun 16.

13.Thursday,October 13-th

Memoryreplay offline

  • Wikenheiser AM,DavidRedishA.The balance offorwardandbackwardhippocampalsequencesshiftsacrossbehavioral states. Hippocampus. 2013 Jan; 23(1):22-9.
  • Jadhav SP, KemereC, German PW, FrankLM.Awake hippocampalsharp-waveripplessupportspatialmemory.Science.2012 Jun 15; 336(6087):1454-8.
  • GirardeauG,CeiA,Zugaro M.Learning-inducedplasticityregulateshippocampalsharpwave-ripple drive. JNeurosci.2014 Apr 9; 34(15):5176-83

14.Tuesday,October 18-th

How the different hippocampal fields work together to subserve memory function. :

  • Sanders H, Renno-Costa C, Idiart M, Lisman J. 2015. Grid Cells and Place Cells: An Integrated View of their Navigational and Memory Function. Trends Neurosci 38: 763-75

15.Thursday,October 20-th

Manipulatingthe engram; false memories.

  • RamirezS, LiuX,Lin PA, Suh J,Pignatelli M, RedondoRL,Ryan TJ, TonegawaS. Creating afalse memoryin thehippocampus.Science. 2013Jul 26; 341(6144):387-91
  • False memories Elizabeth Loftus Ted talk.
  • LismanJ,SchulmanH,Cline H.The molecular basis ofCaMKIIfunction in synaptic andbehaviouralmemory.Nat RevNeurosci. 2002 Mar;3(3):175-90.

16.Thursday,October 27-th

Dopamine as the teacher: Dopamine cells signal reward, saliency and novelty.

  • Cohen JY, HaeslerS, VongL,LowellBB, UchidaN.Neuron-type-specificsignalsforrewardandpunishment in the ventraltegmentalarea.Nature.2012 Jan 18; 482(7383):85-8.doi:
  • LismanJ,Grace AA,DuzelE. AneoHebbianframeworkforepisodic memory;role of dopamine-dependentlateLTP. Trends Neurosci. 2011 Oct; 34(10):536-47.doi: 10.1016/j.tins.2011.07.006. Epub 2011 Aug17. Review

17.Tuesday,November 1-st

Role of sleep in memory

  • GoshenI,BrodskyM,Prakash R, Wallace J,GradinaruV,RamakrishnanC,DeisserothK.Dynamics of retrievalstrategiesforremote memories.Cell. 2011 Oct8;147(3):678-89.doi:10.1016/j.cell.2011.09.033.Epub 2011 Oct 20.
  • Manns JR, Hopkins RO, Squire LR. Semantic memory and the human hippocampus. Neuron. 2003;38(1):127-33.
  • Ferrarelli F, Tononi G. Reduced sleep spindle activity point to a TRN-MD thalamus-PFC circuit dysfunction in schizophrenia. Schizophr Res. 2016

18.Thursday,November 3-rd:

The Neurosciece of classroom learning

  • BallariniF,MartínezMC,DíazPerezM, MoncadaD,Viola H. MemoryinElementarySchoolChildrenIsImprovedbyanUnrelatedNovelExperience.PLoSOne. 2013 Jun 19; 8(6):e66875.Print 2013.
  • KarpickeJD,RoedigerHL3rd. The criticalimportance ofretrievalfor learning.Science.2008Feb 15; 319(5865):966-8. doi: 10.1126/science.1152408.

19.Tuesday,November 8

Alzheimer’s disease

  • Selkoe DJ, Hardy J. The amyloid hypothesis of Alzheimer's disease at 25 years. EMBO Mol Med. 2016;8(6):595-608.

20.Thursday,November 10-th

Procedural memory: habits and the unconscious

  • Procedural memory:
  • Lisman J, Sternberg EJ. Habit and nonhabit systems for unconscious and conscious behavior: implications for multitasking. J Cogn Neurosci. 2013;25(2):273-83

21.Tuesday,November 15-th

Basal ganglia function during reinforcement learning

  • Fee MS, Goldberg JH. A hypothesis for basal ganglia-dependent reinforcement learning in the songbird. Neuroscience. 2011;198:152-70.
  • Freeze BS, Kravitz AV, Hammack N, Berke JD, Kreitzer AC. Control of basal ganglia output by direct and indirect pathway projection neurons. J Neurosci. 2013;33(47):18531-9.
  • Kim KM, Baratta MV, Yang A, Lee D, Boyden ES, Fiorillo CD. Optogenetic mimicry of the transient activation of dopamine neurons by natural reward is sufficient for operant reinforcement. PLoS One. 2012;7(4):e33612.

22.Thursday,November 17-th

Short termmemory: role of persistent firing of neurons

  • Lisman J, Jensen O, Kahana MJ. The Role of Theta-Gamma Oscillations and NMDAR-Dependent LTP. In: Holscher C, editor. Neuronal Mechanisms of Memory Formation. Cambridge, MA, USA: Cambridge University Press; 2001. p. 195-223.
  • Funahashi S, Bruce CJ, Goldman-Rakic PS. Mnemonic coding of visual space in the monkey's dorsolateral prefrontal cortex. J Neurophysiol. 1989;61(2):331-49.
  • Lisman JE, Fellous JM,WangXJ. A role for NMDA-receptorchannels inworkingmemory.Nat

Neurosci. 1998 Aug;1(4):273-5.

  • Harrison, S. A. & Tong, F. Decoding reveals the contents of visual working memory in early visual areas. Nature458, 632–5 (2009).

23.Tuesday,November 22-nd

Role of theta-gamma oscillations in multiitem short-term memory:

  • Bahramisharif A, Jensen O, Jacobs J, Lisman J. Serial representations of items during maintenance of working memory at content-specific cortical sites. Submitted.

24.Tuesday,November 29-th

What are the major unsolved problems in memory research?

25.Thursday,December 1

Review:

26.Tuesday, December 6

Last Class – Review

27. Study days – December 8-9

28.Final exams – December 12-19