Abstract
The BRAIN project recently announced by the president Obama is the reflection of unrelenting human quest for cracking the brain code, the patterns of neuronal activity that define who we are and what we are. While the Brain Activity Mapping proposal has rightly emphasized on the need to develop new technologies for measuring every spike from every neuron, it might be helpful to consider both the theoretical and experimental aspects that would accelerate our search for the organizing principles of the brain code. Here we share several insights and lessons from the similar proposal, namely, Brain Decoding Project that we initiated since 2007. We provide a specific example in our initial mapping of real-time memory traces from one part of the memory circuit, namely, the CA1 region of the mouse hippocampus. We show how innovative behavioral tasks and appropriate mathematical analyses of large datasets can play equally, if not more, important roles in uncovering the specific-to-general feature-coding cell assembly mechanism by which episodic memory, semantic knowledge, and imagination are generated and organized. Our own experiences suggest that the bottleneck of the Brain Project is not only at merely developing additional new technologies, but also the lack of efficient avenues to disseminate cutting edge platforms and decoding expertise to neuroscience community. Therefore, we propose that in order to harness unique insights and extensive knowledge from various investigators working in diverse neuroscience subfields, ranging from perception and emotion to memory and social behaviors, the BRAIN project should create a set of International and National Brain Decoding Centers at which cutting-edge recording technologies and expertise on analyzing large datasets analyses can be made readily available to the entire community of neuroscientists who can apply and schedule to perform cutting-edge research.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Hebb D O. The Organization of Behavior. New York: Wiley, 1949
Wigstrom H, Gustafsson B. On long-lasting potentiation in the hippocampus: a proposed mechanism for its dependence on coincident pre- and postsynaptic activity. Acta Physiol Scand, 1985, 123: 519–522
Bliss T V, Collingridge G L. A synaptic model of memory: long-term potentiation in the hippocampus. Nature, 1993, 361: 31–39
Malenka R C, Nicoll R A. Long-term potentiation-a decade of progress? Science, 1999, 285: 1870–1874
Bi G, Poo M. Synaptic modification by correlated activity: Hebb’s postulate revisited. Annu Rev Neurosci, 2001, 24: 139–166
Tsien J Z. Building a brainier mouse. Sci Am, 2000, 282: 62–68
Abbott L F, Sejnowski T J. Neural Codes and Distributed Representations: Foundations of Neural Computation. Cambridge: Mit Press, 1999
Shamir M, Sompolinsky H. Nonlinear population codes. Neural Comput, 2004, 16: 1105–1136
Sanger T D. Neural population codes. Curr Opin Neurobiol, 2003, 13: 238
Adrian E D. The impulses produced by sensory nerve endings part i. J Physiol, 1926, 61: 49–72
Gross C G, Rocha-Miranda C E, Bender D B. Visual properties of neurons in inferotemporal cortex of the macaque. J Neurophysiol, 1972, 35: 96–111
Fuster J M. Unit activity in prefrontal cortex during delayed-response performance: neuronal correlates of transient memory. J Neurophysiol, 1973, 36: 61-78
Thompson R F. In search of memory traces. Annu Rev Psychol, 2005, 56: 1–23
Zhou Y D, Fuster J M. Mnemonic neuronal activity in somatosensory cortex. Proc Natl Acad Sci USA, 1996, 93: 10533–10537
Bialek W, Rieke F. Reliability and information transmission in spiking neurons. Trends Neurosci, 1992, 15: 428–434
Lestienne R. Spike timing, synchronization and information processing on the sensory side of the central nervous system. Prog Neurobiol, 2001, 65: 545–591
Lin L, Osan R, Tsien J Z. Organizing principles of real-time memory encoding: neural clique assemblies and universal neural codes. Trends Neurosci, 2006, 29: 48–57
Eskandar E N, Richmond B J, Optican L M. Role of inferior temporal neurons in visual memory. I. Temporal encoding of information about visual images, recalled images, and behavioral context. J Neurophysiol, 1992, 68: 1277–1295
Miller E K, Li L, Desimone R. Activity of neurons in anterior inferior temporal cortex during a short-term memory task. J Neurosci, 1993, 13: 1460–1478
Gochin P M, Colombo M, Dorfman G A, et al. Neural ensemble coding in inferior temporal cortex. J Neurophysiol, 1994, 71: 2325–2337
Schmidt E M. Electrodes for many single neuron recordings. Methods Neural Ensemble Record, 1999, 1-23
McNaughton B L, O’Keefe J, Barnes C A. The stereotrode: a new technique for simultaneous isolation of several single units in the central nervous system from multiple unit records. J Neurosci Methods, 1983, 8: 391–397
Buzsaki G. Large-scale recording of neuronal ensembles. Nat Neurosci, 2004, 7: 446–451
Harris K D, Henze D A, Csicsvari J, et al. Accuracy of tetrode spike separation as determined by simultaneous intracellular and extracellular measurements. J Neurophysiol, 2000, 84: 401–414
Georgopoulos A P, Schwartz A B, Kettner R E. Neuronal population coding of movement direction. Science, 1986, 233: 1416–1419
Velliste M, Perel S, Spalding M C, et al. Cortical control of a prosthetic arm for self-feeding. Nature, 2008, 453: 1098–1101
Musallam S, Corneil B D, Greger B, et al. Cognitive control signals for neural prosthetics. Science, 2004, 305: 258–262
Nicolelis M A, Ribeiro S. Seeking the neural code. Sci Am, 2006, 295: 70–77
Donoghue J P. Bridging the brain to the world: a perspective on neural interface systems. Neuron, 2008, 60: 511–521
O’Keefe J, Dostrovsky J. The hippocampus as a spatial map. Preliminary evidence from unit activity in the freely-moving rat. Brain Res, 1971, 34: 171–175
O’Keefe J, Nadel L. The Hippocampus as a Cognitive Map. Oxford: Clarendon Press, 1978
Wilson M A, McNaughton B L. Dynamics of the hippocampal ensemble code for space. Science, 1993, 261: 1055–1058
Redish A D. The hippocampal debate: are we asking the right questions? Behav Brain Res, 2001, 127: 81–98
Kentros C. Hippocampal place cells: the “where” of episodic memory? Hippocampus, 2006, 16: 743–754
Mizumori S J. Hippocampal place fields: a neural code for episodic memory? Hippocampus, 2006, 16: 685–690
Smith D M, Mizumori S J. Hippocampal place cells, context, and episodic memory. Hippocampus, 2006, 16: 716–729
Oler J A, Penley S C, Sava S, et al. Does the dorsal hippocampus process navigational routes or behavioral context? A single-unit analysis. Eur J Neurosci, 2008, 28: 802–812
Tsien J Z, Chen D F, Gerber D, et al. Subregion- and cell type-restricted gene knockout in mouse brain. Cell, 1996, 87: 1317–1326
Tsien J Z, Huerta P T, Tonegawa S. The essential role of hippocampal ca1 nmda receptor-dependent synaptic plasticity in spatial memory. Cell, 1996, 87: 1327–1338
Tang Y P, Shimizu E, Dube G R, et al. Genetic enhancement of learning and memory in mice. Nature, 1999, 401: 63–69
Shimizu E, Tang Y P, Rampon C, et al. Nmda receptor-dependent synaptic reinforcement as a crucial process for memory consolidation. Science, 2000, 290: 1170–1174
Cui Z, Wang H, Tan Y, et al. Inducible and reversible nr1 knockout reveals crucial role of the nmda receptor in preserving remote memories in the brain. Neuron, 2004, 41: 781–793
Cao X, Wang H, Mei B, et al. Inducible and selective erasure of memories in the mouse brain via chemical-genetic manipulation. Neuron, 2008, 60: 353–366
Wang L P, Li F, Wang D, et al. Nmda receptors in dopaminergic neurons are crucial for habit learning. Neuron, 2011, 72: 1055–1066
Tsien J Z. The memory code. Sci Am, 2007, 297: 52–59
Alivisatos A P, Chun M, Church G M, et al. The brain activity map project and the challenge of functional connectomics. Neuron, 2012, 74: 970–974
Mitra P. What’s wrong with the brain activity map proposal. Sci Am, 2013, http://www.scientificamerican.com/article.cfm?id=whats-wrong-
with-the-brain-activity-map-proposal
Somogyi P, Klausberger T. Defined types of cortical interneurone structure space and spike timing in the hippocampus. J Physiol, 2005, 562: 9–26
Klausberger T, Somogyi P. Neuronal diversity and temporal dynamics: the unity of hippocampal circuit operations. Science, 2008, 321: 53–57
Freund T F, Buzsaki G. Interneurons of the hippocampus. Hippocampus, 1996, 6: 347–470
Kuang H, Lin L, Tsien J Z. Temporal dynamics of distinct ca1 cell populations during unconscious state induced by ketamine. PLoS ONE, 2010, 5: e15209
Klausberger T, Magill P J, Marton L F, et al. Brain-state- and cell-type-specific firing of hippocampal interneurons in vivo. Nature, 2003, 421: 844–848
Tukker J J, Fuentealba P, Hartwich K, et al. Cell type-specific tuning of hippocampal interneuron firing during gamma oscillations in vivo. J Neurosci, 2007, 27: 8184–8189
Harvey C D, Coen P, Tank D W. Choice-specific sequences in parietal cortex during a virtual-navigation decision task. Nature, 2012, 484: 62–68
Ziv Y, Burns L D, Cocker E D, et al. Long-term dynamics of ca1 hippocampal place codes. Nat Neurosci, 2013, 16: 264–266
Davis M, Hitchcock J M, Rosen J B. Anxiety and the amygdala: pharmacological and anatomical analysis of the fear-potentiated startle paradigm. Psycho Learn Motivat, 1988, 21: 263–305
LeDoux J E. Emotion, memory and the brain. Sci Am, 1994, 270: 50–57
Clark R E, Squire L R. Classical conditioning and brain systems: the role of awareness. Science, 1998, 280: 77–81
Maren S. Neurobiology of pavlovian fear conditioning. Annu Rev Neurosci, 2001, 24: 897–931
Kim J J, Jung M W. Neural circuits and mechanisms involved in pavlovian fear conditioning: a critical review. Neurosci Biobehav Rev, 2006, 30: 188–202
Clark R E, Zola S. Trace eyeblink classical conditioning in the monkey: a nonsurgical method and behavioral analysis. Behav Neurosci, 1998, 112: 1062–1068
McEchron M D, Bouwmeester H, Tseng W, et al. Hippocampectomy disrupts auditory trace fear conditioning and contextual fear conditioning in the rat. Hippocampus, 1998, 8: 638–646
Knight D C, Cheng D T, Smith C N, et al. Neural substrates mediating human delay and trace fear conditioning. J Neurosci, 2004, 24: 218–228
Matus-Amat P, Higgins E A, Barrientos R M, et al. The role of the dorsal hippocampus in the acquisition and retrieval of context memory representations. J Neurosci, 2004, 24: 2431–2439
Chowdhury N, Quinn J J, Fanselow M S. Dorsal hippocampus involvement in trace fear conditioning with long, but not short, trace intervals in mice. Behav Neurosci, 2005, 119: 1396–1402
Biedenkapp J C, Rudy J W. Context preexposure prevents forgetting of a contextual fear memory: implication for regional changes in brain activation patterns associated with recent and remote memory tests. Learn Mem, 2007, 14: 200–203
Lin L, Osan R, Shoham S, et al. Identification of network-level coding units for real-time representation of episodic experiences in the hippocampus. Proc Natl Acad Sci USA, 2005, 102: 6125–6130
Lin L, Chen G, Xie K, et al. Large-scale neural ensemble recording in the brains of freely behaving mice. J Neurosci Methods, 2006, 155: 28–38
Osan R, Zhu L, Shoham S, et al. Subspace projection approaches to classification and visualization of neural network-level encoding patterns. PLoS ONE, 2007, 2: e404
Chen G, Wang L P, Tsien J Z. Neural population-level memory traces in the mouse hippocampus. PLoS ONE, 2009, 4: e8256
Tulving E. Episodic and semantic memory. In: Tulving E, Donaldson W, eds. Organization of Memory. New York: Academic Press, 1972. 381–402
Squire L R, Zola S M. Episodic memory, semantic memory, and amnesia. Hippocampus, 1998, 8: 205–211
Cohen N J, Eichenbaum H. Memory, Amnesia, and the Hippocampal System. Cambridge: MIT Press, 1993
Kapur N, Friston K J, Young A, et al. Activation of human hippocampal formation during memory for faces: a pet study. Cortex, 1995, 31: 99–108
Duzel E, Cabeza R, Picton T W, et al. Task-related and item-related brain processes of memory retrieval. Proc Natl Acad Sci USA, 1999, 96: 1794–1799
Maguire E A, Frith C D, Rudge P, et al. The effect of adult-acquired hippocampal damage on memory retrieval: an fMRI study. Neuroimage, 2005, 27: 146–152
McIntosh A M, Harrison L K, Forrester K, et al. Neuropsychological impairments in people with schizophrenia or bipolar disorder and their unaffected relatives. Br J Psychiatry, 2005, 186: 378–385
Burianova H, Grady C L. Common and unique neural activations in autobiographical, episodic, and semantic retrieval. J Cogn Neurosci, 2007, 19: 1520–1534
Ryan L, Cox C, Hayes S M, et al. Hippocampal activation during episodic and semantic memory retrieval: comparing category production and category cued recall. Neuropsychologia, 2008, 46: 2109–2121
Wang D V, Tsien J Z. Convergent processing of both positive and negative motivational signals by the VTA dopamine neuronal populations. PLoS ONE, 2011, 6: e17047
Frey U, Morris R G. Synaptic tagging: implications for late maintenance of hippocampal long-term potentiation. Trends Neurosci, 1998, 21: 181–188
Frey S, Frey J U. ‘Synaptic tagging’ and’ cross-tagging’ and related associative reinforcement processes of functional plasticity as the cellular basis for memory formation. Prog Brain Res, 2008, 169: 117–143
Frey S, Bergado-Rosado J, Seidenbecher T, et al. Reinforcement of early long-term potentiation (early-LTP) in dentate gyrus by stimulation of the basolateral amygdala: heterosynaptic induction mechanisms of late-LTP. J Neurosci, 2001, 21: 3697–3703
Lin L, Chen G, Kuang H, et al. Neural encoding of the concept of nest in the mouse brain. Proc Natl Acad Sci USA, 2007, 104: 6066–6071
Hampson R E, Pons T P, Stanford T R, et al. Categorization in the monkey hippocampus: a possible mechanism for encoding information into memory. Proc Natl Acad Sci USA, 2004, 101: 3184–3189
Osan R, Chen G, Feng R, et al. Differential consolidation and pattern reverberations within episodic cell assemblies in the mouse hippocampus. PLoS ONE, 2011, 6: e16507
Warrington E K, Shallice T. Category specific semantic impairments. Brain, 1984, 107(Pt 3): 829–854
Tranel D, Damasio H, Damasio A R. A neural basis for the retrieval of conceptual knowledge. Neuropsychologia, 1997, 35: 1319–1327
Hodges J R, Graham K S. Episodic memory: insights from semantic dementia. Philos Trans R Soc Lond B Biol Sci, 2001, 356: 1423–1434
Messas C S, Mansur L L, Castro L H. Semantic memory impairment in temporal lobe epilepsy associated with hippocampal sclerosis. Epilepsy Behav, 2008, 12: 311–316
Quiroga R Q, Reddy L, Kreiman G, et al. Invariant visual representation by single neurons in the human brain. Nature, 2005, 435: 1102–1107
Quiroga R Q, Kreiman G, Koch C, et al. Sparse but not ‘grandmother-cell’ coding in the medial temporal lobe. Trends Cogn Sci, 2008, 12: 87–91
Zhu D, Li K, Guo L, et al. Dicccol: dense individualized and common connectivity-based cortical landmarks. Cereb Cortex, 2013, 23: 786–800
Yuan Y, Jiang X, Zhu D, et al. Meta-analysis of functional roles of dicccols. Neuroinformatics, 2013, 11: 47–63
Addis D R, Pan L, Vu M A, et al. Constructive episodic simulation of the future and the past: distinct subsystems of a core brain network mediate imagining and remembering. Neuropsychologia, 2009, 47: 2222–2238
Author information
Authors and Affiliations
Corresponding authors
Additional information
This article is published with open access at Springerlink.com
Rights and permissions
Open Access This article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
About this article
Cite this article
Tsien, J.Z., Li, M., Osan, R. et al. On brain activity mapping: insights and lessons from Brain Decoding Project to map memory patterns in the hippocampus. Sci. China Life Sci. 56, 767–779 (2013). https://doi.org/10.1007/s11427-013-4521-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11427-013-4521-1