NMDA receptor dependent functions of hippocampal networks in spatial navigation and memory formation

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1 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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35 session # trial # surgery pre-training recording 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) interneuron pyramidal time (ms) mean AC (msec) time (ms) prob < 70% prob > 70% prob > 80% prob > 90% ISVD (%) > ± th

36 µ µ

37 a TRAINING PLACE SEQUENCE b speed (cm/sec) normalized trial length CTR KO average velocity (cm/sec) CTR TRAINING PLACE SEQUENCE KO

38 ISV D = 100 V v V 0.26 A PV, v 0.26 v PV %

39 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

40 <

41 a long short b PLACE SEQUENCE reward localization score c CTR KO pre-training session surgery recording session d trials fraction trials fraction CTR 1 0 KO experiment block PLACE SEQUENCE serial random < x

42 trials fraction ratio correct choices a b ** ** short long 0 CTR KO CTR KO CTR KO Training PLACE SEQUENCE short Training long * CTR KO ratio correct choices ratio correct choices c d short short SEQUENCE long PLACE long *** % e probability correct outcome f % 20 % choice LONG # * % g * localization score long short * 0 short long 0 pretraining recording 55 pretraining recording 2 < 2 <

43 2 < 2 < < 2 2 < 2 < < 2 < 2 < < < 2 < 2 <

44 2 < 2 < < 2 2 < < < <

45 fraction CTR KO area PF *** ratio in-field FR increase *** Hz max FR # # of PFs *** bits/spike Spatial Information *** sparsity *** < < <

46 9y a CTR Tr PLACE b KO SEQ 7.6 PLACE Tr 5.5 c SEQ * ** d C TR KO C 2.5 firing rate (Hz) 2.3 TR KO 2.3 Sidx 2.5 Pidx * TRAINING PLACE SEQUENCE CTR e KO 20 CTR KO Pidx 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@

47 idx idx < idx idx o idx < < < idx idx < < idx idx < < <

48 < idx idx < idx idx < idx 8 * SEQ. short SEQ. long idx < S Idx CTR

49 P idx S idx session block CTR KO idx idx idx < < idx < < < idx <

50 fraction of place cells CTR KO Spatial Information (spikes/bin) 0 sessions 1-7 sessions < < < < < 1 idx < fraction CTR KO

51 Tr Distribution of P idx in SEQ trials SEQ CTR PC fraction KO n.sig sig Tr P idx Distribution of S idx in PLACE trials PLACE 0.2 CTR 0.2 P idx KO PC fraction S idx S idx th < < idx

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66 long short a b reward PLACE SEQUENCE

67 a frequency (Hz) CTR normalized power in a short Tr trial log power 90 KO log power departure normalized distance goal departure normalized distance goal b log normalized power CTR KO frequency (Hz) log normalized power c Hz Hz Hz CTR KO CTR KO CTR KO th th

68 < a Pearson s R(speed x power) CTR KO frequency (Hz) b normalized powerspeed modulation Dep arm Middle arms Goal arm CTR Hz Hz Hz 0 KO c speed (cm/s) CTR KO < < <

69 < <

70 log power ratio a CTR PLACE SEQ 95% c.i. (shuffling) b log power ratio KO c ratio LG/HG * 5 * TR PLACE SEQ frequency (Hz) frequency (Hz) d TRAINING PLACE SEQUENCE e ratio LG/HG CTR KO session block session block session block 7 ratio LG/HG S L L CTR CTR KO 0 CTR KO 0 CTR KO TRAINING PLACE SEQUENCE S S KO L < < <

71 < < < < < < <

72 freq (Hz) a b 2 mv 100 ms (rad) power (normalized) c CTR d KO 120 gamma LG HG 330 e coherence f coherence * * freq (Hz) TrT PLACE 0.6 SEQ freq (Hz) < > < <

73 < < < <

74 Kappa concentration of preferred theta phases 2 ** CTR ** KO ** * LG HG TrT PLACESEQ 0 TrT PLACESEQ < < < <

75 A theta LG HG fraction HG LG 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 **** *** *** KO LG HG LG HG PLACE SEQUENCE

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85 o th th i,m ppc 0 = P Nm P Nm j=1 k6=j sin ( j,m ) sin ( k,m )+cos ( j,m ) cos ( k,m ) N m(n m 1)

86 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

87 ' p R ' =âr p 2 i i x i

88 PPC a pyramidal CTR KO b PPC interneurons frequency (Hz) frequency (Hz)

89 2 < < < < < <

90 a c PPC e -180 o o Theta phase locking 180 o session b CTR KO d performance (%) f fraction mod. cells 20 ppc of mod. cells Theta locking all spikes * correct incorrect P idx 5 S idx peak PPC to theta peak PPC to theta idx idx

91 o < 2 < < < < < < idx idx idx idx < idx idx < <

92 1 a Theta phase locking b c CTR KO fraction mod. cells ppc of mod. cells * avg P idx PYR avg S idx PYR peak PPC peak PPC < idx idx idx < <

93 a fraction b c 90 d 90 peak ppc mod. cells * ** LG Locking HG Locking ** LG HG LG HG < < < < <

94 idx idx < 2 < < < < <

95 a avg S idx PYR r = 0.35 p = PPC LG b PPC LG in SEQ. Trials r = p < PPC LG in PLACE Trials idx < < < idx < < <

96 a trial 1 trial 2 trial 3 trial 4 trial 5 phase (deg) precession R-value phase range (deg) position (cm) b c d CTR KO CTR KO CTR KO e CTR TrT PLACE SEQ. KO slope (deg/cm) f CTR * * place field size(cm) spike phase KO 180 *

97 o < < < < <

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101 o

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103 % ± <

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110 µ µ

111 ISV D = 100 V v V 0.26 A PV, v 0.26 v PV %

112

113 a b c CTR CTR KO KO normalized firing rate max distance (cm) distance (cm) trial # place field size (cm) d per session *** CTR KO per trial CTR KO < < ± ± ± <

114 A B D CTR jitter trial # fraction of place cells jitter(cm) 60 *** jitter (cm) CTR KO * trial # distance (cm) KO distance (cm) 0 normalized FR 1 fraction of place cells C *** jitter (cm) E trial * ** trial ± ± < ± ± ±

115 < < < < < < < < < < <

116 < < < < < ± ±0.005,NR1 KO =0.022± <

117 A CTR trial number B slope (deg) 0-4 CTR KO normalized slope phase (deg) C distance (cm) normalized firing rate trial number KO phase range (deg) normalized slope phase (deg) distance (cm) 8 4 distance D covered (cm) normalized firing rate

118 < < < < < < < <

119 fraction place cells A B C stability index CTR KO *** Pearson's R (first-second half) N trials trials to stable PF * 0.4 * * * * * threshold R stability index *** r = session cm D Place Field Size Spatial Information ** [1 2] * session [9 10] bits/spike * * [1 2] session [9 10] st nd < < < < < < < < < < < < < < < < <

120 * < A B C CTR KO trial ** trial * *** D trial < < < < < < < < < < <

121 < <

122 A CTR KO B cell # norm distance CTR norm distance from departure C same-distance norm distance norm FR norm distance same-location *** *** *** *** D norm distance norm distance KO norm distance from departure 1 < 5

123 < < < 5

124 fraction of place fields A PF location along maze CTR KO normalized position of PF COM B place field size(cm) normalized position of PF COM < < < <

125 < <

126 th th

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141 TRAINING TRIAL CA1 CA3 EC LG HG

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143 CA1 CA1 SC EC SC EC CA3 PP CA3 PP DG CONTROL DG NR1-KO

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