UvA-DARE (Digital Academic Repository) NMDA receptor dependent functions of hippocampal networks in spatial navigation and memory formation de Oliveira Cabral, H. Link to publication Citation for published version (APA): de Oliveira Cabral, H. (2014). NMDA receptor dependent functions of hippocampal networks in spatial navigation and memory formation General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulations If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: http://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. UvA-DARE is a service provided by the library of the University of Amsterdam (http://dare.uva.nl) Download date: 25 Dec 2018
NMDA receptor dependent functions of hippocampal networks in spatial navigation and memory formation HENRIQUE DE OLIVEIRA CABRAL HENRIQUE DE OLIVEIRA CABRAL NMDA receptor dependent functions of hippocampal networks in spatial navigation and memory formation
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session # trial # surgery pre-training recording 1 2 3 4 5 10 1 2 3 4 15 1 8 15 18 T T T T T T T T T T T T T T T T T T T T T T T T T T T T T T T T T T T T P P P T T T T T T T T T T T T T T T T T T T T T T training trial P T T T T T T T T T P T T T T T T T T T T T T T T T T T T P P P T T T T T T T T T T T T P P P T T T T T T T T T T T T P P P T T T T T T T T T probe trial firing rate (Hz) 41.4 31.1 20. 10.5 interneuron pyramidal 16.65 2.05-30 0 30 time (ms) 0.25 9.63 15.15 20.6 mean AC (msec) -30 0 30 time (ms) 26.21 31.74 2.55 prob < 70% prob > 70% prob > 80% prob > 90% 71.04 53.92 36.79 19.67 ISVD (%) > ± th
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a TRAINING PLACE SEQUENCE b speed (cm/sec) 40 20 0 0 40 20 0 0 0.5 1 0.5 1 40 20 0 0 0.5 1 40 20 0 0 0.5 1 normalized trial length 40 20 0 0 40 20 0 0 0.5 1 0.5 1 CTR KO average velocity (cm/sec) 20 16 12 8 4 0 CTR TRAINING PLACE SEQUENCE KO
ISV D = 100 V v V 0.26 A PV, v 0.26 v PV %
x P f(x) p(x)f(x)log2 F SpatialInf ormation =, F x x x x Sparsity = (P p(x)f(x)) 2 P (p(x)f(x) 2 ) idx idx idx o o
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a long short b PLACE SEQUENCE reward localization score c 95 85 75 65 55 CTR KO 1 3 5 7 9 pre-training session surgery 1 3 5 7 9 11 13 15 recording session d trials fraction trials fraction CTR 1 0 KO 1 0 1 2 3 4 5 experiment block PLACE SEQUENCE serial random < x
trials fraction ratio correct choices a b 1 0.8 0.6 0.4 0.2 1 0.8 0.6 0.4 0.2 0 ** ** short long 0 CTR KO CTR KO CTR KO Training PLACE SEQUENCE short 1 0.8 0.6 0.4 0.2 0 Training long 1 0.8 0.6 0.4 0.2 0 * CTR KO ratio correct choices ratio correct choices c 1 0.8 0.6 0.4 0.2 0 d 1 0.8 0.6 0.4 0.2 0 short short SEQUENCE long 1 0.8 0.6 0.4 0.2 0 1 0.8 0.6 0.4 0.2 0 PLACE 1 0.8 0.6 0.4 0.2 0 long 1 0.8 0.6 0.4 0.2 0 *** % e 60 40 20 probability correct outcome f 60 40 % 20 % choice LONG # * % 85 75 65 g * localization score long short * 0 short long 0 pretraining recording 55 pretraining recording 2 < 2 <
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fraction CTR KO area PF 0.16 0.08 0 *** ratio in-field FR increase 12 8 4 0 *** Hz 6 4 2 0 max FR # 1.6 0.8 0 # of PFs *** bits/spike Spatial Information 0.8 0.4 0 *** 0.04 0.02 0 sparsity *** < < <
9y a CTR Tr PLACE 13.2 8.7 b KO SEQ 7.6 PLACE Tr 5.5 c SEQ 4.2 72 3.3 2.9 11.1 11.3 3.2 3.8 * ** 6 6 4 4 2 1.8 7.2 0 d 3.0 2.0 2.9 1.5 0 C 2.4 5.1 3.4 TR KO 4.2 2 C 2.5 firing rate (Hz) 2.3 TR KO 2.3 Sidx 2.5 Pidx 1.4 3 * TRAINING PLACE SEQUENCE 2 1 0 CTR 1.9 12.3 2.3 11.3 13.1 e KO 20 CTR KO 3.4 21.2 11.1 15.8 Pidx 10 4.8 0-10 -5 5 15 Sidx 6B;m`2 kxe hq [m MiB7v i?2b2 2z2+ib- r2 + H+mH i2/ irq bbkbh `Biv BM/B+2b, TH +2 USidx V M/ b2[m2m+2 BM/2t Uaidx VX h?2 }`bi r b + H+mH i2/ b i?2 S2 `@ bqmƕb +Q``2H ibqm #2ir22M }`BM; ` i2 K Tb BM i` BMBM; i`b Hb M/ T`Q#2 i`b Hb- mbbm; i?2 Qp2`H TTBM; TQ`iBQM Q7 i?2 `Qmi2bX aidx Bb i?2 S2 `bqmƕb +Q``2H ibqm #2ir22M i?2 }`BM; ` i2 K Tb BM i` BMBM; i`b Hb M/ i?2 }`BM; ` i2 K T BM b2[m2m+2@bi` i2;v i`b Hb- `Qi i2/ #v dko iq K F2 i` BMBM; M/ T`Q#2 /2T `im`2 `Kb +QBM+B/2X "Qi? +Q``2H ibqmb r2`2 MQ`K HBx2/ #v K2 Mb Q7 b?m 2/ +QM/BiBQM Ub22 J2i?Q/bVX "Qi? *h_ M/ L_R@EP KB+2 b?qr2/ 2H2p i2/ Sidx p Hm2b- b2p2` H@7QH/?B;?2` i? M b?m 2/ +QM@
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fraction of place cells 0.08 0.04 0 CTR 1 2 3 4 5 6 7 0.08 0.04 KO Spatial Information (spikes/bin) 0 sessions 1-7 sessions 8-15 1 2 3 4 5 6 7 < < < < < 1 idx < fraction 0.8 0.6 0.4 0.2 0 CTR KO
Tr Distribution of P idx in SEQ trials SEQ CTR 8.7 5.6 PC fraction 0.2 0.15 0.1 0.05 0-10 0 10 0.25 0.2 0.15 0.1 0.05 KO 0-10 0 10 n.sig sig Tr P idx Distribution of S idx in PLACE trials PLACE 0.2 CTR 0.2 P idx KO 16.8 4.1 PC fraction 0.15 0.1 0.05 0.15 0.1 0.05 0-10 0 10 S idx 0-10 0 10 S idx th < < idx
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a frequency (Hz) 90 70 50 30 CTR normalized power in a short Tr trial 14 10 6 2 log power 90 KO 70 50 30 14 10 6 2 log power 10 10 departure normalized distance goal departure normalized distance goal b log normalized power 10 3 10 1 10-1 7 CTR KO 28 4560 90 120 frequency (Hz) log normalized power c 40 6-12 Hz 23-40 Hz 55-95 Hz 5 1.2 30 4 3 0.8 20 2 0.4 10 1 0 0 0 CTR KO CTR KO CTR KO th th
< a Pearson s R(speed x power) 0.8 0.6 0.4 0.2 0 CTR KO 7 28 45 60 90 120 frequency (Hz) b normalized powerspeed modulation 0.6 0.5 0.4 0.3 0.2 0.1 0 Dep arm Middle arms Goal arm CTR 0.6 0.5 0.4 0.3 0.2 6-12 Hz 23-40 Hz 0.1 55-95 Hz 0 KO c speed (cm/s) 22 18 14 10 8 CTR KO < < <
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log power ratio a 1.04 1.02 1 CTR PLACE SEQ 95% c.i. (shuffling) b log power ratio 1.04 1.02 1 KO c ratio LG/HG * 5 * 4 3 2 1 TR PLACE SEQ 0.98 0 20 40 60 80 100 120 0.98 0 20 40 60 80 100 120 frequency (Hz) frequency (Hz) d TRAINING PLACE SEQUENCE e ratio LG/HG 7 5 3 1-3 4-6 7-9 10-12 13-15 1 CTR KO 7 5 3 1-3 4-6 7-9 10-12 13-15 1 5 3 1-3 4-6 7-9 1 10-12 13-15 session block session block session block 7 ratio LG/HG 7 6 5 4 3 S L 7 6 5 4 3 0 L CTR 2 2 2 1 1 1 0 CTR KO 0 CTR KO 0 CTR KO TRAINING PLACE SEQUENCE S 7 6 5 4 3 S KO L < < <
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freq (Hz) a b 2 mv 100 ms 140 120 100 80 60 40 20 0 1 2 3 4 5 6 (rad) 60 50 40 30 20 10 power (normalized) c CTR 150 210 d KO 120 gamma 240 90 270 60 300 30 180 0 150 210 120 240 90 270 60 300 330 30 180 0 LG HG 330 e coherence f coherence 0.6 0.5 0.4 0.6 * * 0.4 0.3 0.2 0 0 50 100 150 freq (Hz) TrT PLACE 0.6 SEQ. 0.5 0.4 0.6 0.4 0.3 0.2 0 0 50 100 150 freq (Hz) < > < <
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A theta LG HG fraction 60 40 20 HG LG 0-2 0 2 4 6 8 log ratio B TRAINING, all periods SEQUENCE, LG SEQUENCE, HG departure 16.3 departure 12.9 departure 8.6 goal goal goal C overlap index CTR 6 **** *** *** 5 4 3 2 1 0 KO LG HG LG HG PLACE SEQUENCE
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m ppc 1 = P M P M P Nm P Nm m=1 l6=m j=1 sin ( j,m ) sin ( k,l )+cos ( j,m ) cos ( k,l ) k=1 P M P M m=1 l6=m NmN l ppc 1 < i i i th â R(a) =r 1 P 2 n n j=1 cos j 2 ax j + 1 P 2 n n j=1 sin j 2 ax j
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PPC a 0.015 0.01 pyramidal CTR KO b PPC 0.025 0.02 0.015 interneurons 0.005 0.01 0.005 0 10 20 30 40 50 60 70 80 90 100 frequency (Hz) 0 10 20 30 40 50 60 70 80 90 100 frequency (Hz)
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a c PPC e -180 o 15 90 180 0 0.56 0.04 0.03 0.02 0.01 0 o Theta phase locking 180 o 270 1-3 4-6 7-9 session 8-12 13-15 0.69 85 75 65 b CTR KO d performance (%) f fraction mod. cells 20 ppc of mod. cells 1 0.8 0.6 0.4 0.2 0 0.04 0.03 0.02 0.01 0 Theta locking 0.008 all spikes 0.004 * 90 180 0 270 correct incorrect P idx 5 S idx 10-5 0 0.04 0.08 peak PPC to theta 0 0 0.04 0.08 peak PPC to theta idx idx
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1 a Theta phase locking b c 90 0.8 CTR KO 180 0.41 0 270 0.58 fraction mod. cells ppc of mod. cells 0.6 0.4 0.2 0 0.06 0.04 0.02 0 * avg P idx PYR avg S idx PYR 16 12 8 4 0 0 0.1 0.2 peak PPC 16 12 8 4 0 0 0.04 0.08 0.12 peak PPC < idx idx idx < <
a fraction b c 90 d 90 peak ppc mod. cells 0.03 0.3 * ** LG Locking HG Locking ** 0.02 180 0 180 0 0.15 0.10 0.01 0.29 0 0 LG HG LG HG 0.31 0.36 270 270 2 < < < < <
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a avg S idx PYR 12 8 4 r = 0.35 p = 0.04 0-0.005 0.015 0.035 PPC LG b PPC LG in SEQ. Trials 0.02-0.04 r = -0.64 p < 0.05-0.1 0 0.1 0.2 PPC LG in PLACE Trials idx < < < idx < < <
a trial 1 trial 2 trial 3 trial 4 trial 5 phase (deg) precession R-value phase range (deg) 600 400 200 0 100 150 100 150 100 150 100 150 100 150 position (cm) b c d CTR KO CTR KO CTR KO -0.4-0.8 e 0 0-100 -200 CTR TrT PLACE SEQ. KO slope (deg/cm) 0-10 -20 f CTR * * 90 180 0 270 place field size(cm) 16 8 0 spike phase KO 180 * 90 270 0
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a b c CTR CTR KO 120 2 2 4 4 KO 11.9 15.0 6 6 80 8 8 10 10 12 40 8.7 18.4 12 14 14 16 0 normalized firing rate max 0 43 86 129 172 0 43 86 129 172 0 distance (cm) distance (cm) trial # place field size (cm) d per session *** 40 30 20 10 0 CTR KO per trial CTR KO < < ± ± ± <
A B D CTR jitter trial # fraction of place cells 0.12 0.08 0.04 jitter(cm) 60 *** 40 20 0 jitter (cm) 16 14 12 10 CTR KO * trial # 0 43 86 129 172 distance (cm) KO 0 43 86 129 172 distance (cm) 0 normalized FR 1 fraction of place cells C 0.06 0.6 *** 0.04 0.02 0 0 50 100 150 jitter (cm) 0.4 0.2 0 0-1 -0.6-0.2 0.2 0.6 1 E 8 0.7 0.65 0.6 0.55 0.5 0.45 5 10 15 trial * ** 5 10 15 trial ± ± < ± ± ±
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A CTR trial number B slope (deg) 0-4 CTR KO -8-12 -16-50 -150-250 normalized slope phase (deg) C 16 12 0 0 40 80 120 160 200 distance (cm) 8 4 0-100 -200 normalized firing rate trial number KO phase range (deg) -50-150 -250 normalized slope phase (deg) 16 12 0 40 80 120 160 200 0 distance (cm) 8 4 distance D covered (cm) 16 12 8 4 0 normalized firing rate
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fraction place cells A B C 0.05 0.04 0.03 0.02 0.01 stability index CTR KO *** 0-0.5 0 0.5 1 Pearson's R (first-second half) N trials 15 10 5 1 0 0.2 trials to stable PF * 0.4 * * * * * 0.6 0.8 threshold 1 0.5 0.4 R 0.3 0.2 stability index *** r = 0.12 2 4 6 8 10 session cm D 130 110 90 70 Place Field Size Spatial Information ** [1 2] * session [9 10] bits/spike 0.6 0.5 0.4 0.3 0.2 * * [1 2] session [9 10] st nd < < < < < < < < < < < < < < < < <
* < A B C 1.8 1.6 1.4 1.2 1 CTR KO 2 4 6 8 10 12 14 trial ** 1.4 1.3 1.2 1.1 1 2 4 6 8 1012 14 trial * 1 0.5 0-0.5-1 -1.5 *** D 0-0.04-0.08-0.12-0.16-0.2 2 4 6 8 10 12 14 trial < < < < < < < < < < <
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A CTR KO B cell # 50 100 150 200 250 50 100 150 200 norm distance 1 0.8 0.6 0.4 0.2 0 0.2 CTR 0.4 0.6 0.8 norm distance from departure 0.1 0.2 0.3 0.4 0.5 0.6 0.7 C same-distance norm distance norm FR norm distance 0 0.2 0.4 0.6 0.8 1 same-location 0 0.05 0.10.15 0.20.25 0.30.35 *** *** *** *** D 0.18 0.14 0.1 0.06-0.4-0.2 0 0.2 0.4 0.4 0.3 0.2 0.1 0-0.4-0.2 0 0.2 0.4 norm distance norm distance 1 0.8 0.6 0.4 0.2 0 0 0.2 KO 0.4 0.6 0.8 norm distance from departure 1 < 5
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fraction of place fields A 0.2 0.15 0.1 0.05 0 0.05 0.15 PF location along maze CTR KO 0.25 0.35 0.45 0.55 0.65 0.75 0.85 0.95 normalized position of PF COM B place field size(cm) 90 80 70 60 50 40 30 20 0 0.2 0.4 0.6 0.8 1 normalized position of PF COM < < < <
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TRAINING TRIAL CA1 CA3 EC LG HG
CA1 CA1 SC EC SC EC CA3 PP CA3 PP DG CONTROL DG NR1-KO
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