title: Spike-timing theory of working memory.
abstract: Working memory (WM) is the part of the brain's memory system that provides temporary storage and manipulation of information necessary for cognition. Although WM has limited capacity at any given time, it has vast memory content in the sense that it acts on the brain's nearly infinite repertoire of lifetime long-term memories. Using simulations, we show that large memory content and WM functionality emerge spontaneously if we take the spike-timing nature of neuronal processing into account. Here, memories are represented by extensively overlapping groups of neurons that exhibit stereotypical time-locked spatiotemporal spike-timing patterns, called polychronous patterns; and synapses forming such polychronous neuronal groups (PNGs) are subject to associative synaptic plasticity in the form of both long-term and short-term spike-timing dependent plasticity. While long-term potentiation is essential in PNG formation, we show how short-term plasticity can temporarily strengthen the synapses of selected PNGs and lead to an increase in the spontaneous reactivation rate of these PNGs. This increased reactivation rate, consistent with in vivo recordings during WM tasks, results in high interspike interval variability and irregular, yet systematically changing, elevated firing rate profiles within the neurons of the selected PNGs. Additionally, our theory explains the relationship between such slowly changing firing rates and precisely timed spikes, and it reveals a novel relationship between WM and the perception of time on the order of seconds.
authors.affiliation: The Neurosciences Institute, San Diego, California, United States of America.
authors.forename: Botond
authors.initials: B
authors.lastname: Szatmáry
authors.forename: Eugene M
authors.initials: EM
authors.lastname: Izhikevich
mesh_terms: D000818:Animals; D001921:Brain / Q000502:physiology; D003198:Computer Simulation; D057567:Memory, Long-Term / Q000502:physiology; D008570:Memory, Short-Term / Q000502:physiology*; D008959:Models, Neurological; D009415:Nerve Net / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D013569:Synapses / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology; D013998:Time Perception / Q000502:physiology
references.citation: Neuron. 2007 Feb 1;53(3):427-38
references.pmid: 17270738
references.citation: Science. 2008 Sep 5;321(5894):1322-7
references.pmid: 18772431
references.citation: Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):13481-6
references.pmid: 8942960
references.citation: Psychol Rev. 1956 Mar;63(2):81-97
references.pmid: 13310704
references.citation: Neural Comput. 2005 Mar;17(3):691-713
references.pmid: 15802011
references.citation: J Neurosci. 1999 Nov 1;19(21):9587-603
references.pmid: 10531461
references.citation: Proc Natl Acad Sci U S A. 2007 Mar 20;104(12):5175-80
references.pmid: 17360369
references.citation: Neural Comput. 2006 Feb;18(2):245-82
references.pmid: 16378515
references.citation: Behav Brain Res. 1998 Mar;91(1-2):1-13
references.pmid: 9578434
references.citation: IEEE Trans Neural Netw. 2003;14(6):1569-72
references.pmid: 18244602
references.citation: J Neurophysiol. 2000 May;83(5):3031-41
references.pmid: 10805698
references.citation: Nat Neurosci. 2004 Feb;7(2):170-7
references.pmid: 14730306
references.citation: Neuron. 2009 May 14;62(3):413-25
references.pmid: 19447096
references.citation: Cereb Cortex. 2003 Nov;13(11):1196-207
references.pmid: 14576211
references.citation: PLoS Comput Biol. 2007 Sep;3(9):1679-700
references.pmid: 17845070
references.citation: Neuron. 2009 Feb 26;61(4):621-34
references.pmid: 19249281
references.citation: Neuron. 2005 Feb 3;45(3):419-31
references.pmid: 15694328
references.citation: J Neurosci. 1993 Aug;13(8):3406-20
references.pmid: 8340815
references.citation: Trends Neurosci. 2001 Aug;24(8):455-63
references.pmid: 11476885
references.citation: J Neurophysiol. 1992 Aug;68(2):605-19
references.pmid: 1527578
references.citation: Cereb Cortex. 2004 Aug;14(8):933-44
references.pmid: 15142958
references.citation: Science. 2008 Mar 14;319(5869):1543-6
references.pmid: 18339943
references.citation: Prog Neurobiol. 2004 Sep;74(1):1-58
references.pmid: 15381316
references.citation: Science. 1971 Aug 13;173(3997):652-4
references.pmid: 4998337
references.citation: Nature. 2007 Aug 9;448(7154):709-13
references.pmid: 17581587
references.citation: J Neurophysiol. 2003 Nov;90(5):3441-54
references.pmid: 12773500
references.citation: J Neurophysiol. 1989 Feb;61(2):331-49
references.pmid: 2918358
references.citation: Nature. 2000 Mar 16;404(6775):285-9
references.pmid: 10749211
references.citation: Front Neurosci. 2008 Jul 14;2(1):114-22
references.pmid: 18982114
references.citation: J Neurophysiol. 1985 Nov;54(5):1346-62
references.pmid: 4078619
references.citation: Nat Neurosci. 1998 Aug;1(4):273-5
references.pmid: 10195158
references.citation: Science. 1997 Jan 10;275(5297):213-5
references.pmid: 8985014
references.citation: J Neurosci. 2006 Jun 21;26(25):6704-15
references.pmid: 16793878
references.citation: J Neurophysiol. 1994 Feb;71(2):437-53
references.pmid: 8176419
references.citation: Psychon Bull Rev. 2001 Sep;8(3):568-78
references.pmid: 11700909
references.citation: Science. 2008 Feb 22;319(5866):1108-11
references.pmid: 18292344
references.citation: J Neurophysiol. 2005 Oct;94(4):2275-83
references.pmid: 16160088
references.citation: J Cogn Neurosci. 2010 Nov;22(11):2530-40
references.pmid: 19925206
references.citation: Nat Neurosci. 2007 Jan;10(1):100-7
references.pmid: 17173043
references.citation: Nat Rev Neurosci. 2005 May;6(5):399-407
references.pmid: 15861182
references.citation: PLoS Comput Biol. 2008 May 16;4(5):e1000073
references.pmid: 18464917
references.citation: Nat Neurosci. 2000 Sep;3(9):919-26
references.pmid: 10966623
references.citation: Nat Neurosci. 2008 Jul;11(7):823-33
references.pmid: 18516033
references.citation: Nat Neurosci. 2009 Jul;12(7):913-8
references.pmid: 19525943
references.citation: Cereb Cortex. 2003 May;13(5):435-43
references.pmid: 12679290
references.citation: Psychopharmacology (Berl). 2004 Jun;174(1):3-16
references.pmid: 15118803
references.citation: Neuron. 1993 Feb;10(2):115-25
references.pmid: 8094962
references.citation: Cereb Cortex. 2007 Oct;17(10):2443-52
references.pmid: 17220510
references.citation: Nature. 1995 Jul 6;376(6535):33-6
references.pmid: 7596429