Andersen P, Bliss TV, Lomo T, Olsen LI, Skrede KK. Lamellar organization of
hippocampal excitatory pathways. Acta Physiol Scand. 1969 May-Jun;76(1):4A-5A.
Aoki Y, Igata H, Ikegaya Y, Sasaki T. The Integration of Goal-Directed Signals onto
Spatial Maps of Hippocampal Place Cells. Cell Rep. 2019 Apr 30;27(5):15161527.e5.
Bender F, Gorbati M, Cadavieco MC, Denisova N, Gao X, Holman C, Korotkova T,
Ponomarenko A. Theta oscillations regulate the speed of locomotion via a
hippocampus to lateral septum pathway. Nat Commun. 2015 Oct 12;6:8521.
Bittner KC, Milstein AD, Grienberger C, Romani S, Magee JC. Behavioral time scale
synaptic plasticity underlies CA1 place fields. Science. 2017 Sep
8;357(6355):1033-1036.
Brandon MP, Koenig J, Leutgeb JK, Leutgeb S. New and distinct hippocampal place
codes are generated in a new environment during septal inactivation. Neuron.
2014 May 21;82(4):789-96.
Brun VH, Leutgeb S, Wu HQ, Schwarcz R, Witter MP, Moser EI, Moser MB. Impaired
spatial representation in CA1 after lesion of direct input from entorhinal cortex.
Neuron. 2008 Jan 24;57(2):290-302.
49
Brzosko Z, Zannone S, Schultz W, Clopath C, Paulsen O. Sequential neuromodulation
of Hebbian plasticity offers mechanism for effective reward-based navigation. Elife.
2017 Jul 10;6:e27756.
Capocchi G, Zampolini M, Larson J. Theta burst stimulation is optimal for induction of
LTP at both apical and basal dendritic synapses on hippocampal CA1 neurons.
Brain Res. 1992 Sep 25;591(2):332-6.
Ciocchi S, Passecker J, Malagon-Vina H, Mikus N, Klausberger T. Brain computation.
Selective information routing by ventral hippocampal CA1 projection neurons.
Science. 2015 May 1;348(6234):560-3.
Colgin LL. Mechanisms and functions of theta rhythms. Annu Rev Neurosci. 2013 Jul
8;36:295-312.
Drieu C, Todorova R, Zugaro M. Nested sequences of hippocampal assemblies during
behavior support subsequent sleep replay. Science. 2018 Nov 9;362(6415):675679.
Drieu C, Zugaro M. Hippocampal Sequences During Exploration: Mechanisms and
Functions. Front Cell Neurosci. 2019 Jun 13;13:232.
Ekstrom AD, Kahana MJ, Caplan JB, Fields TA, Isham EA, Newman EL, Fried I.
Cellular networks underlying human spatial navigation. Nature. 2003 Sep
50
11;425(6954):184-8.
Eliav T, Geva-Sagiv M, Yartsev MM, Finkelstein A, Rubin A, Las L, Ulanovsky N.
Nonoscillatory Phase Coding and Synchronization in the Bat Hippocampal
Formation. Cell. 2018 Nov 1;175(4):1119-1130.e15.
Fernández-Ruiz A, Oliva A, Nagy GA, Maurer AP, Berényi A, Buzsáki G. EntorhinalCA3 Dual-Input Control of Spike Timing in the Hippocampus by Theta-Gamma
Coupling. Neuron. 2017 Mar 8;93(5):1213-1226.e5.
Fernández-Ruiz A, Oliva A, Fermino de Oliveira E, Rocha-Almeida F, Tingley D,
Buzsáki G. Long-duration hippocampal sharp wave ripples improve memory.
Science. 2019 Jun 14;364(6445):1082-1086.
Frank LM, Eden UT, Solo V, Wilson MA, Brown EN. Contrasting patterns of receptive
field plasticity in the hippocampus and the entorhinal cortex: an adaptive filtering
approach. J Neurosci. 2002 May 1;22(9):3817-30.
Fyhn M, Molden S, Witter MP, Moser EI, Moser MB. Spatial representation in the
entorhinal cortex. Science. 2004 Aug 27;305(5688):1258-64.
Fyhn M, Hafting T, Witter MP, Moser EI, Moser MB. Grid cells in mice. Hippocampus.
2008;18(12):1230-8.
Girardeau G, Benchenane K, Wiener SI, Buzsáki G, Zugaro MB. Selective suppression
51
of hippocampal ripples impairs spatial memory. Nat Neurosci. 2009
Oct;12(10):1222-3.
Gridchyn I, Schoenenberger P, O'Neill J, Csicsvari J. Assembly-Specific Disruption of
Hippocampal Replay Leads to Selective Memory Deficit. Neuron. 2020 Apr
22;106(2):291-300.e6.
Grosmark AD, Buzsáki G. Diversity in neural firing dynamics supports both rigid and
learned hippocampal sequences. Science. 2016 Mar 25;351(6280):1440-3.
Hafting T, Fyhn M, Molden S, Moser MB, Moser EI. Microstructure of a spatial map in
the entorhinal cortex. Nature. 2005 Aug 11;436(7052):801-6.
Hales JB, Schlesiger MI, Leutgeb JK, Squire LR, Leutgeb S, Clark RE. Medial entorhinal
cortex lesions only partially disrupt hippocampal place cells and hippocampusdependent place memory. Cell Rep. 2014 Nov 6;9(3):893-901.
Harris KD, Henze DA, Hirase H, Leinekugel X, Dragoi G, Czurkó A, Buzsáki G. Spike
train dynamics predicts theta-related phase precession in hippocampal pyramidal
cells. Nature. 2002 Jun 13;417(6890):738-41.
Hori E, Nishio Y, Kazui K, Umeno K, Tabuchi E, Sasaki K, Endo S, Ono T, Nishijo H.
Place-related neural responses in the monkey hippocampal formation in a virtual
space. Hippocampus. 2005;15(8):991-6.
52
Igata H, Ikegaya Y, Sasaki T, Prioritized experience replays on a hippocampal predictive
map for learning. Proc Natl Acad Sci U S A. 2021, 118 (1) e2011266118.
Isaac JT, Buchanan KA, Muller RU, Mellor JR. Hippocampal place cell firing patterns
can induce long-term synaptic plasticity in vitro. J Neurosci. 2009 May
27;29(21):6840-50.
Jadhav SP, Kemere C, German PW, Frank LM. Awake hippocampal sharp-wave ripples
support spatial memory. Science. 2012 Jun 15;336(6087):1454-8.
Jones MW, Wilson MA. Phase precession of medial prefrontal cortical activity relative to
the hippocampal theta rhythm. Hippocampus. 2005;15(7):867-73.
Kentros C, Hargreaves E, Hawkins RD, Kandel ER, Shapiro M, Muller RV. Abolition of
long-term stability of new hippocampal place cell maps by NMDA receptor
blockade. Science. 1998 Jun 26;280(5372):2121-6.
King C, Recce M, O'Keefe J. The rhythmicity of cells of the medial septum/diagonal
band of Broca in the awake freely moving rat: relationships with behaviour and
hippocampal theta. Eur J Neurosci. 1998 Feb;10(2):464-77.
Knierim JJ, Zhang K. Attractor dynamics of spatially correlated neural activity in the
limbic system. Annu Rev Neurosci. 2012;35:267-85.
Larson J, Lynch G. Induction of synaptic potentiation in hippocampus by patterned
53
stimulation involves two events. Science. 1986 May 23;232(4753):985-8.
Larson J, Munkácsy E. Theta-burst LTP. Brain Res. 2015 Sep 24;1621:38-50.
Lewis PR, Shute CC, Silver A. Confirmation from choline acetylase analyses of a
massive cholinergic innervation to the rat hippocampus. J Physiol. 1967
Jul;191(1):215-24.
Malhotra S, Cross RW, van der Meer MA. Theta phase precession beyond the
hippocampus. Rev Neurosci. 2012;23(1):39-65.
Mehta MR, Lee AK, Wilson MA. Role of experience and oscillations in transforming a
rate code into a temporal code. Nature. 2002 Jun 13;417(6890):741-6.
Muller RU, Kubie JL, Ranck JB Jr. Spatial firing patterns of hippocampal complex-spike
cells in a fixed environment. J Neurosci. 1987 Jul;7(7):1935-50.
O'Keefe J, Dostrovsky J. The hippocampus as a spatial map. Preliminary evidence from
unit activity in the freely-moving rat. Brain Res. 1971 Nov;34(1):171-5.
O'Keefe J, Recce ML. Phase relationship between hippocampal place units and the EEG
theta rhythm. Hippocampus. 1993 Jul;3(3):317-30.
Park SW, Jang HJ, Kim M, Kwag J. Spatiotemporally random and diverse grid cell spike
patterns contribute to the transformation of grid cell to place cell in a neural
network model. PLoS One. 2019 Nov 14;14(11):e0225100.
54
Qasim ES, Fried I, Jacobs J. Phase precession in the human hippocampus and
entorhinal cortex. bioRxiv 2020.09.06.285320.
Robinson NTM, Priestley JB, Rueckemann JW, Garcia AD, Smeglin VA, Marino FA,
Eichenbaum H. Medial Entorhinal Cortex Selectively Supports Temporal Coding
by Hippocampal Neurons. Neuron. 2017 May 3;94(3):677-688.e6.
Sanders H, Rennó-Costa C, Idiart M, Lisman J. Grid Cells and Place Cells: An
Integrated View of their Navigational and Memory Function. Trends Neurosci.
2015 Dec;38(12):763-775.
Schlesiger MI, Cannova CC, Boublil BL, Hales JB, Mankin EA, Brandon MP, Leutgeb
JK, Leibold C, Leutgeb S. The medial entorhinal cortex is necessary for temporal
organization of hippocampal neuronal activity. Nat Neurosci. 2015
Aug;18(8):1123-32.
Schoenenberger P, O'Neill J, Csicsvari J. Activity-dependent plasticity of hippocampal
place maps. Nat Commun. 2016 Jun 10;7:11824.
Shirvalkar PR, Rapp PR, Shapiro ML. Bidirectional changes to hippocampal thetagamma comodulation predict memory for recent spatial episodes. Proc Natl Acad
Sci U S A. 2010 Apr 13;107(15):7054-9.
SHUTE CC, LEWIS PR. CHOLINESTERASE-CONTAINING SYSTEMS OF THE BRAIN
OF THE RAT. Nature. 1963 Sep 21;199:1160-4.
55
Ulanovsky N, Moss CF. Hippocampal cellular and network activity in freely moving
echolocating bats. Nat Neurosci. 2007 Feb;10(2):224-33.
Van Cauter T, Poucet B, Save E. Unstable CA1 place cell representation in rats with
entorhinal cortex lesions. Eur J Neurosci. 2008 Apr;27(8):1933-46.
van der Meer MA, Redish AD. Theta phase precession in rat ventral striatum links place and
reward information. J Neurosci. 2011 Feb 23;31(8):2843-54.
Wang Y, Romani S, Lustig B, Leonardo A, Pastalkova E. Theta sequences are essential for
internally generated hippocampal firing fields. Nat Neurosci. 2015 Feb;18(2):282-8.
Zhang SJ, Ye J, Miao C, Tsao A, Cerniauskas I, Ledergerber D, Moser MB, Moser EI.
Optogenetic dissection of entorhinal-hippocampal functional connectivity. Science.
2013 Apr 5;340(6128):1232627.
Zheng C, Bieri KW, Hsiao YT, Colgin LL. Spatial Sequence Coding Differs during Slow and
Fast Gamma Rhythms in the Hippocampus. Neuron. 2016 Jan 20;89(2):398-408.
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