New life in an old idea: The synaptic plasticity and memory hypothesis revisited

Martin, Stephen J.; Morris, Richard

doi:10.1002/hipo.10107

Cited by 381 publications

(270 citation statements)

References 306 publications

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“…This is in line with recent observations in the hippocampal CA1 area, showing that corticosterone can enhance long-term potentiation (LTP)-presently the best-described neurobiological substrate of learning and memory (Martin and Morris 2002;Morris 2003)-when the hormone is applied around the time of LTP induction , while it suppresses LTP when given several hours in advance (Alfarez et al 2002;Wiegert et al 2005).…”

supporting

confidence: 91%

Corticosterone time-dependently modulates β-adrenergic effects on long-term potentiation in the hippocampal dentate gyrus

Pu¹,

Krugers²,

Joëls³

2007

Learn. Mem.

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Previous experiments in the hippocampal CA1 area have shown that corticosterone can facilitate long-term potentiation (LTP) in a rapid non-genomic fashion, while the same hormone suppresses LTP that is induced several hours after hormone application. Here, we elaborated on this finding by examining whether corticosterone exerts opposite effects on LTP depending on the timing of hormone application in the dentate gyrus as well. Moreover, we tested rapid and delayed actions by corticosterone on ␤-adrenergic-dependent changes in LTP. Unlike the CA1 region, our in vitro field potential recordings show that rapid effects of corticosterone do not influence LTP induced by mild tetanization in the hippocampal dentate gyrus, unless GABA A receptors are blocked. In contrast, the ␤-adrenergic agonist isoproterenol does initiate a slow-onset, limited amount of potentiation. When corticosterone was applied concurrently with isoproterenol, a further enhancement of synaptic strength was identified, especially during the early stage of potentiation. Yet, treatment with corticosterone several hours in advance of isoproterenol fully prevented any effect of isoproterenol on LTP. This emphasizes that corticosterone can regulate ␤-adrenergic modulation of synaptic plasticity in opposite directions, depending on the timing of hormone application.

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supporting

confidence: 91%

Corticosterone time-dependently modulates β-adrenergic effects on long-term potentiation in the hippocampal dentate gyrus

Pu¹,

Krugers²,

Joëls³

2007

Learn. Mem.

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“…Accompanying the learning impairment was a deficit in the induction of LTP; this further supports the hypothesis that deficits in LTP contribute to the impairment in spatial memory (33). Importantly, knockout mice for the M2 muscarinic receptor also show reduced hippocampal LTP, a similar pattern of learning deficit in the Barnes maze, and impaired reversal learning (32).…”

Section: Forebrain Cholinergic Tone Is Involved In Spontaneous Locomosupporting

confidence: 72%

“…Indeed, accumulating evidence suggests that LTD also plays an important role in learning and memory (34). LTD seems to be particularly important in tasks requiring the learning of a new context, in conjunction with the rapid extinction of information that is no longer relevant (33). Importantly, efficient learning seems to require proper balance between LTP and LTD (33,34).…”

Section: Forebrain Cholinergic Tone Is Involved In Spontaneous Locomomentioning

confidence: 99%

Elimination of the vesicular acetylcholine transporter in the forebrain causes hyperactivity and deficits in spatial memory and long-term potentiation

Martyn¹,

Jaeger

Magalhães³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Basal forebrain cholinergic neurons, which innervate the hippocampus and cortex, have been implicated in many forms of cognitive function. Immunolesion-based methods in animal models have been widely used to study the role of acetylcholine (ACh) neurotransmission in these processes, with variable results. Cholinergic neurons have been shown to release both glutamate and ACh, making it difficult to deduce the specific contribution of each neurotransmitter on cognition when neurons are eliminated. Understanding the precise roles of ACh in learning and memory is critical because drugs that preserve ACh are used as treatment for cognitive deficits. It is therefore important to define which cholinergic-dependent behaviors could be improved pharmacologically. Here we investigate the contributions of forebrain ACh on hippocampal synaptic plasticity and cognitive behavior by selective elimination of the vesicular ACh transporter, which interferes with synaptic storage and release of ACh. We show that elimination of vesicular ACh transporter in the hippocampus results in deficits in long-term potentiation and causes selective deficits in spatial memory. Moreover, decreased cholinergic tone in the forebrain is linked to hyperactivity, without changes in anxiety or depression-related behavior. These data uncover the specific contribution of forebrain cholinergic tone for synaptic plasticity and behavior. Moreover, these experiments define specific cognitive functions that could be targeted by cholinergic replacement therapy.Alzheimer's disease | Morris water maze | synaptic vesicle | Barnes maze T he mechanisms that underlie the formation of hippocampaldependent spatial memory have been broadly explored (1). However, the neurochemical basis underlying changes in the strength of synaptic connections necessary for memories to persist is still not precisely understood. In the case of the hippocampus, mechanisms for memory processing include mRNA-dependent (2) and mammalian target of rapamycin (mTOR)-mediated protein synthesis (3) as well as a sequence of biochemical events shared with or closely similar to that of long-term potentiation (LTP) (2). Indeed, the consolidation of two different aversive tasks (4) and of spatial recognition memory (5) is accompanied by LTP of the CA3-CA1 synapse and can be occluded by a preceding LTP.The basal forebrain cholinergic system, which innervates the hippocampus and cortex, has been suggested to modulate LTP in the hippocampus (6-9) and has been implicated in many forms of behavior (10). In addition, spatial memory has also been suggested to depend on cholinergic activity (10), although there are numerous controversies surrounding which behaviors acetylcholine (ACh) regulates (11, 12). Moreover, in few studies cholinergic denervation did not affect expression of LTP (13). Understanding the precise roles of ACh in learning and memory is of importance because in different types of dementia cholinergic function is decreased (14), and manipulations that boost ACh levels at synapses are used a...

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“…The most direct evidence of engram cells should come from gain-of-function experiments, where a population of neurons that are considered responsible for a particular memory are selectively labeled and activated artificially to mimic their natural activity. If such manipulation causes the recall of that memory, then this provides evidence that the selected population of neurons is sufficient for the memory, thus argues the selected neuronal population is the neuronal basis for the engram of this particular memory (Martin and Morris 2002). However, this type of gain-of-function experiments are technically challenging, as one has to be able to correctly isolate the neurons involved in one particular memory from their seemingly indistinguishable neighbors and activate 6 them with proper spatial and temporal precision.…”

Section: Optogenetic Activation Of Memory Engram Cellsmentioning

confidence: 98%

Identification and Manipulation of Memory Engram Cells

Liu¹,

Ramirez

Redondo³

et al. 2014

Cold Spring Harb Symp Quant Biol

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How memories are formed and stored in the brain remains a fascinating question in neuroscience.Here we discuss the memory engram theory, our recent attempt to identify and manipulate memory engram cells in the brain with optogenetics, and how these methods are used to address questions such as how false memory is formed, and how the valence of a memory can be changed in the brain. 3How and where memory is stored in the brain network is one of the fundamental questions in brain and cognitive sciences. At the onset of the 20 th century, a German biologist Richard Semon proposed the engram theory of memory (Semon 1923), but the theory was nearly completely ignored by his contemporary and subsequent brain researchers, until Daniel Schactor, James Eich, and Endel Tulving revived the theory in the late 1970s (Schacter et al. 1978). Semon's memory engram theory was built on two fundamental postulates termed the "Law of Engraphy" and the "Law of Ecphory" for memory storage and memory retrieval, respectively. The law of Engraphy posits: "All simultaneous excitations (derived from experience)…with in our organisms form a connected simultaneous complex of excitations which, as such, acts engraphically, that is to say leaves behind it a connected, and to that extent, unified engram-complex" (Semon 1923). The Law of Ecphory on the other hand posits: "The partial return of an energetic situation which has fixed itself engraphically acts in an ecphoric sense upon a simultaneous engram-complex" (Semon 1923).Semon's conceptualizations of the memory process were novel at his time, and were remarkably predictive of the contemporary concepts of memory storage and retrieval. For instance, Semon's memory retrieval process contained the concept of "pattern completion," which was advanced years later (Marr 1970;Nakazawa et al. 2003;Leutgeb et al. 2004). However, Semon did not elaborate the biological basis of the "simultaneous excitations" nor "a connected, unified engram-complex." This is not surprising considering that his theory was put forward nearly a century before the development of molecular, cellular, and genetic biology, and sophisticated imaging and electrophysiological technologies for the analysis of the nervous system.Incorporating the current knowledge about neurons, synaptic connections, and neuronal circuits, These studies were consistent with the notion that episodic memories are stored in the MTLs.As to the nature of memory engrams-enduring physical and chemical changes induced by learning-the guiding hypothesis has been Donald Hebb's theory, which posits that neurons encoding memory stimuli undergo enduring strengthening of some of their synapses through their co-activation with presynaptic cells: neurons that "fire together wire together" (Hebb 1949).Starting with Tim Bliss and Terje Lomo's discovery of long-term potentiation (Bliss and Lomo 5 1973), which supports Hebb's hypothesis, a large amount of studies have been directed to the characterization of LTP and other facets of synaptic plasticity, and thei...

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New life in an old idea: The synaptic plasticity and memory hypothesis revisited

Cited by 381 publications

References 306 publications

Corticosterone time-dependently modulates β-adrenergic effects on long-term potentiation in the hippocampal dentate gyrus

Corticosterone time-dependently modulates β-adrenergic effects on long-term potentiation in the hippocampal dentate gyrus

Elimination of the vesicular acetylcholine transporter in the forebrain causes hyperactivity and deficits in spatial memory and long-term potentiation

Identification and Manipulation of Memory Engram Cells

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