Memory and the Computational Brain: Why Cognitive Science will Transform Neuroscience

nn.2391.pdf......Page 0
Figure 1 Tempero-ammonic input controls postsynaptic spike timing of CA1 pyramidal neurons during theta oscillation.......Page 15
References......Page 17
Figure 3 Enforcement of potentiation and depression by external input during theta oscillation.......Page 16
Figure 1 Ventral hippocampal commissural stimulation interrupts SPW-Rs and hippocampal cell discharges without changing global sleep architecture.......Page 18
Figure 2 Suppression of SPW-Rs interferes with memory consolidation.......Page 19
Figure 1 Intact rapid, automatic and nonconscious detection of fearful \nfaces in the absence of the amygdala.......Page 20
References......Page 21
Figure 1 Lesion study: mean preferred distances from the experimenter.......Page 22
Figure 2 fMRI study: activation of the amygdala by close (relative to far) interpersonal distance.......Page 23
AP2 regulates basal progenitor fate in a region- and layer-specific manner in the developing cortex......Page 24
Figure 1 AP2γ expression in the mouse brain.......Page 25
Figure 2 Cell division and basal progenitor identity in the cerebral cortex of AP2γ−/− mice at mid-neurogenesis.......Page 26
Figure 6 Neurogenesis at E14 in the cerebral cortex of AP2γ−/− mice.......Page 28
Figure 7 Visual physiology of wild-type and AP2γ−/− cortices.......Page 29
Region- and layer-specific functions of AP2......Page 30
References......Page 31
Electrophysiology.......Page 33
Data analysis.......Page 34
Figure 4 AP2γ overexpression in the \ndeveloping cortex.......Page 27
Sox2 deletion causes hippocampal defects with NSC loss......Page 48
Figure 1 Sox2 conditional null allele, SOX2 protein ablation by nestin-Cre in mutant embryonic brain and in vivo morphological defects of nestin-cre Sox2-deleted mutants (Sox2null).......Page 49
Figure 3 Sox2-deleted mutant brains have defective Shh and Wnt3a mRNA expression.......Page 50
Figure 5 Stimulation of the Shh signaling pathway rescues hippocampal NSC and neurogenesis in Sox2 mutants.......Page 51
Figure 6 Sox2 deletion in adult brain leads to rapid loss of radial glia cells and of cell proliferation in the hippocampus dentate gyrus.......Page 52
Figure 7 Impaired maintenance of Sox2null NSCs in culture and rescue by extracellular factors.......Page 53
Figure 8 Shh is a direct target of SOX2.......Page 54
References......Page 55
Sox2-GFP lentivirus transduction.......Page 57
ChIP and EMSA.......Page 58
The CaV2 1 subunit UNC-2 localizes to presynaptic zones......Page 59
Figure 1 GFP-tagged UNC-2 localizes to presynaptic puncta in sensory neurons and motor neurons.......Page 60
Figure 3 calf-1 encodes a type I transmembrane protein.......Page 62
Figure 4 CALF-1 acts cell-autonomously in neurons and localizes to endoplasmic reticulum.......Page 63
Figure 5 Structure-function analysis of \nCALF-1.......Page 64
Figure 6 CALF-1 and UNC-36 have related trafficking functions.......Page 65
Figure 7 Acute CALF-1 expression transports UNC-2 from the cell body to the synapse.......Page 66
Swimming assay.......Page 68
Statistical analysis.......Page 69
References......Page 67
Figure 2 Presynaptic GFPUNC-2 puncta are lost in calf-1(ky867) mutants.......Page 61
EFHC1 interacts with microtubules to regulate cell division and cortical development......Page 70
Figure 2 EFHC1 is a MAP.......Page 71
Figure 3 EFHC1 is necessary for mitotic spindle organization and M phase progression.......Page 72
Figure 4 EFHC1 loss of function induces microtubule bundling and apoptosis.......Page 73
Figure 5 Essential role of EFHC1 in radial neuronal migration.......Page 74
Figure 6 EFHC1 is crucial for mitosis and cell cycle exit of cortical progenitors.......Page 75
Figure 7 EFHC1 is implicated in the locomotion of postmitotic neurons.......Page 76
References......Page 77
In vitro microtubule binding assays.......Page 79
Statistical analysis.......Page 80
Epac2 induces synapse remodeling and depression and its disease-associated forms alter spines......Page 81
Figure 1 Epac2 is present in synapses in cultured cortical pyramidal neurons.......Page 82
Figure 2 Epac2 activation induces dendritic spine shrinkage, reduces presynaptic contact and enhances spine motility and turnover.......Page 83
Figure 3 Epac2 interacts with GluR2/3-containing AMPAR and removes them from spines.......Page 84
Figure 4 Epac2 activation depresses AMPAR-mediated synaptic transmission.......Page 85
Figure 5 Dopamine D1/D5-like receptors modulate Rap activity, spine morphology and GluR2 surface expression.......Page 86
Figure 6 Epac2 interacts with neuroligins.......Page 87
References......Page 90
Time-lapse imaging.......Page 91
Statistical analysis.......Page 92
Figure 7 Disease-associated missense mutations affect Epac2 function.......Page 88
Figure 8 Epac2 missense mutants affect spine morphology.......Page 89
Neuron-glia communication via EphA4/ephrin-A3 modulates LTP through glial glutamate transport......Page 93
Figure 2 Ephrin-A3 is required for TBS-induced LTP.......Page 94
Figure 4 Astrocytic glutamate transporter currents.......Page 95
Figure 5 Glutamate levels, postsynaptic responses to high frequency stimulation and pharmacological rescue of LTP.......Page 96
Figure 6 Ephrin-A3 overexpression in astrocytes reduces glutamate transporters.......Page 97
Figure 7 Ephrin-A3 overexpression in astrocytes increases susceptibility to excitotoxicity and seizures.......Page 98
References......Page 99
Immunofluorescence and immunohistochemistry.......Page 101
Statistical analysis.......Page 102
Nicotine activates TRPA1......Page 103
Figure 6 TRPA1 mediates the airway constriction reflex triggered by nasal instillation of nicotine and mustard oil.......Page 106
Figure 7 Menthol inhibits nicotine-induced activation of TRPA1.......Page 107
References......Page 109
Statistics.......Page 110
Figure 2 Nicotine activates TRPA1 in cell-free inside-out patches.......Page 104
Figure 4 TRPA1 activation is prevented by the nAChR inhibitor mecamylamine, but is unaffected by hexamethonium.......Page 105
Suppression of hippocampal TRPM7 protein prevents delayed neuronal death in brain ischemia......Page 111
Figure 1 Suppression of TRPM7 expression in adult rat hippocampal neurons.......Page 112
Figure 5 Persistence of function in surviving TRPM7-deficient CA1 neurons 30 d after ischemia.......Page 114
Figure 6 TRPM7 deficiency prevents loss of memory functions in rats subjected to global ischemia.......Page 115
DISCUSSION......Page 116
References......Page 117
Contextual fear memory.......Page 119
Statistics.......Page 120
Figure 3 TRPM7 suppression in vivo imparts resilience to DND.......Page 113
A ganglion cell type is sensitive to approaching motion......Page 121
Figure 2 PV-5 ganglion cells respond to approaching motion even in the absence of dimming.......Page 122
Figure 6 The rapid inhibitory pathway is mediated by an electrical synapse.......Page 124
Figure 8 The functional properties of AII amacrine cells are consistent with the rapid inhibitory signal in PV-5 ganglion cells.......Page 126
Implementation of approach sensitivity......Page 127
References......Page 128
Immunohistochemistry.......Page 130
Computational model.......Page 131
Figure 4 PV-5 ganglion cells receive a rapid inhibitory input required to suppress responses to lateral motion.......Page 123
Figure 7 PV-5 cells receive an inhibitory input from AII amacrine cells.......Page 125
Coding of stimulus sequences by population responses in visual cortex......Page 132
Figure 1 Population responses to an oriented stimulus.......Page 133
Figure 3 Predicting the membrane potential responses of the population to the full stimulus sequence.......Page 134
Figure 5 Predicting the interactions between population responses to successive orientations.......Page 135
Figure 6 Unexplained persistence of population responses after stimulus offset.......Page 136
Figure 7 Decoding stimulus orientation from the population responses.......Page 137
DISCUSSION......Page 138
References......Page 139
Bayesian decoder.......Page 140
RESULTS......Page 142
Figure 1 Grid fields repeat across arms with similar running directions.......Page 143
Figure 4 Representations were reset near the turning points.......Page 145
Figure 5 Shortcut experiments suggest a path-integration mechanism.......Page 146
Figure 6 Firing pattern of hippocampal place cells in the hairpin maze.......Page 147
Figure 7 Preserved two-dimensional grid representations in a virtual hairpin maze.......Page 148
References......Page 149
Population vector construction and correlation procedures.......Page 150
Histology.......Page 151
Figure 3 Population analysis for all trials and all rats.......Page 144
Transformation of nonfunctional spinal circuits into functional states after the loss of brain input......Page 152
Figure 1 Accessing spinal locomotor circuits 1 week after the interruption of all supraspinal input.......Page 153
Figure 5 Functional remodeling of spinal circuits after rehabilitative locomotor training.......Page 156
Figure 6 Effects of velocity-dependent afferent input on motor patterns.......Page 157
Accessing the circuits and receptors in lumbosacral spinal cord......Page 159
Methods......Page 160
Limb endpoint trajectory.......Page 162
Statistical analyses .......Page 163
References......Page 161
Figure 3 Site-specific effects of EES during standing and stepping.......Page 154
Figure 4 Rehabilitation locomotor training enabled by pharmacological and EES interventions improves stepping ability.......Page 155
Figure 8 Effects of direction-dependent afferent input on motor patterns.......Page 158
Classical conditioning in the vegetative and minimally conscious state......Page 164
Figure 2 Learning during the anticipatory interval.......Page 165
Figure 3 Single-subject measures of learning during the anticipatory interval.......Page 166
Table 1  Learning differences at the group level......Page 167
Table 2  Cortical atrophy partially explains anticipatory activity (learning) in trace conditioning......Page 168
Figure 6 Intact latencies, but smaller amplitudes, in event-related auditory potentials in DOCs.......Page 169
References......Page 170
Statistical analysis at the group level.......Page 171