NMDA spikes enhance action potential generation during sensory input

Palmer, Lucy M.; Shai, Adam S.; Reeve, James E.; Anderson, Harry L.; Paulsen, Ole; Larkum, Matthew E.

doi:10.1038/nn.3646

Cited by 272 publications

(279 citation statements)

References 51 publications

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“…NMDARs are co-localized with AMPA receptors, however, so they cannot receive inputs from sources that differ from AMPA receptors, and they cannot first be integrated separately before being used to modulate response to the integrated RF input. We now see that, as suggested by a theory of learning closely related to coherent infomax , a solution to this problem is provided by the evidence for apical amplification (Larkum, 2013;Palmer et al, 2014). The RF inputs from the basal dendrites are integrated at the somatic spike initiation zone.…”

Section: Flourishing By Increasing Prediction Successmentioning

confidence: 84%

“…It is therefore important to note that although BAC firing may be a mechanism by which apical amplification is achieved in Layer 5 cells, it may be achieved in other ways in other classes of pyramidal cell (Palmer, et al, 2014). The crucial feature of these discoveries is that they show that pyramidal cells have intracellular mechanisms by which contextual amplification can be implemented, thus providing further evidence that it is widely distributed throughout the cortex.…”

Section: Modulation That Amplifies Responses To Rf Inputmentioning

confidence: 97%

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On the functions, mechanisms, and malfunctions of intracortical contextual modulation

Phillips

Clark

Silverstein

2015

Neuroscience & Biobehavioral Reviews

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A broad neuron-centric conception of contextual modulation is reviewed and re-assessed in the light of recent neurobiological studies of amplification, suppression, and synchronization. Behavioural and computational studies of perceptual and higher cognitive functions that depend on these processes are outlined, and evidence that those functions and their neuronal mechanisms are impaired in schizophrenia is summarized. Finally, we compare and assess the long-term biological functions of contextual modulation at the level of computational theory as formalized by the theories of coherent infomax and free energy reduction. We conclude that those theories, together with the many empirical findings reviewed, show how contextual modulation at the neuronal level enables the cortex to flexibly adapt the use of its knowledge to current circumstances by amplifying and grouping relevant activities and by suppressing irrelevant activities.

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Section: Flourishing By Increasing Prediction Successmentioning

confidence: 84%

Section: Modulation That Amplifies Responses To Rf Inputmentioning

confidence: 97%

On the functions, mechanisms, and malfunctions of intracortical contextual modulation

Phillips

Clark

Silverstein

2015

Neuroscience & Biobehavioral Reviews

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“…[36][37][38] These calcium potentials carry incoming signals actively along the dendrite toward the cell body. Moreover, both in vitro and in vivo studies suggest that information impinging upon the peripheral dendritic branches is carried toward the mentioned calcium spike [39][40][41][42] Thus, there is an active, two-stage signaling process along the apical dendrites of pyramidal neurons: first, input to the distal tuft dendrites is carried toward the main dendrite by means of NMDA spikes; second, calcium potentials triggered close to the main bifurcation relay the signals to the soma ( fig. 2B).…”

Section: The Effects Of General Anesthetics On Apical Dendrites Of Pymentioning

confidence: 99%

The Role of Dendritic Signaling in the Anesthetic Suppression of Consciousness

Meyer

2015

Anesthesiology

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Despite considerable progress in the identification of the molecular targets of general anesthetics, it remains unclear how these drugs affect the brain at the systems level to suppress consciousness. According to recent proposals, anesthetics may achieve this feat by interfering with corticocortical topdown processes, that is, by interrupting information flow from association to early sensory cortices. Such a view entails two immediate questions. First, at which anatomical site, and by virtue of which physiological mechanism, do anesthetics interfere with top-down signals? Second, why does a breakdown of top-down signaling cause unconsciousness? While an answer to the first question can be gleaned from emerging neurophysiological evidence on dendritic signaling in cortical pyramidal neurons, a response to the second is offered by increasingly popular theoretical frameworks that place the element of prediction at the heart of conscious perception. Science magazine posed this question in a special section titled "What don't we know?," dedicated to the greatest challenges of contemporary science. 1 "Scientists are chipping away at the drugs' effects on individual neurons," the article reads, "but understanding how they render us unconscious will be a tougher nut to crack." This prediction proved correct: a decade later, we have expanded considerably our knowledge of the molecular targets of general anesthetics, but it remains enigmatic how these drugs affect the brain at the systems level. Why does the potentiation of γ-aminobutyric acid (GABA) receptors caused by propofol or desflurane cause unconsciousness? How are the brain's computational processes affected by this and other molecular mechanisms of anesthetics, so that patients undergoing surgery cease to experience their surrounds in terms of sight, sound, and touch? Anesthesiologists and cognitive neuroscientists alike have been captivated by these questions and have proposed a number of models in an attempt to answer them, such as Flohr's "information processing theory of anesthesia," 2 Alkire's "thalamic consciousness switch hypothesis," 3-6 Mashour's "cognitive unbinding paradigm," 7,8 John and Prichep's "anesthetic cascade," 9 or Hudetz's "forgotten present." 10,11 We shall return to some of these frameworks in a later section of the article.One recent development is particularly intriguing. Given that the most striking feature of general anesthesia is an interruption of the patient's ability to perceive the environment, it would appear intuitive for anesthetics to interfere primarily with bottom-up information flow along the sensory pathways, that is, with the signals that carry perceptual information from the thalamus to the primary sensory cortices and on to unimodal and multimodal association cortices. However, the very opposite appears to be the case. Several recent studies-carried out in both humans and animals, and using a variety of different anesthetic agents-have investigated differences in directional corticocortical connectivity bet...

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“…Dendritic spikes are now a well-documented phenomenon; they have been seen both in slices and in vivo (Svoboda et al, 1997;Kamondi et al, 1998;Gasparini et al, 2004;Losonczy and Magee, 2006;Spruston, 2008;Major et al, 2013;Smith et al, 2013;Palmer et al, 2014). This is of interest in the present context because each time a dendritic spike is generated, the conditions for its generation must, by necessity, be satisfied, and these include coordinated assaults of spikes on a segment of dendrite, assaults intense enough that they are unlikely to arise as part of random spike fluctuations.…”

Section: Discussionmentioning

confidence: 96%

“…The interplay between N-methyl-D-aspartate (NMDA) receptors, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, and Mg 2+ ions results in responsiveness to spike coincidence and repetition (Larkum et al, 2009;Major et al, 2013;Palmer et al, 2014). Since a large class of surprising events is distinguished by nothing more than spike coincidence and repetition, these receptor systems make for highly effective surprise detectors.…”

Section: The Linkage Between Ltp and Surprising Eventsmentioning

confidence: 99%

Synaptic and extrasynaptic traces of long-term memory: the ID molecule theory

Legéndy

2016

Reviews in the Neurosciences

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AbstractIt is generally assumed at the time of this writing that memories are stored in the form of synaptic weights. However, it is now also clear that the synapses are not permanent; in fact, synaptic patterns undergo significant change in a matter of hours. This means that to implement the long survival of distant memories (for several decades in humans), the brain must possess a molecular backup mechanism in some form, complete with provisions for the storage and retrieval of information. It is found below that the memory-supporting molecules need not contain a detailed description of mental entities, as had been envisioned in the ‘memory molecule papers’ from 50 years ago, they only need to contain unique identifiers of various entities, and that this can be achieved using relatively small molecules, using a random code (‘ID molecules’). In this paper, the logistics of information flow are followed through the steps of storage and retrieval, and the conclusion reached is that the ID molecules, by carrying a sufficient amount of information (entropy), can effectively control the recreation of complex multineuronal patterns. In illustrations, it is described how ID molecules can be made to revive a selected cell assembly by waking up its synapses and how they cause a selected cell assembly to ignite by sending slow inward currents into its cells. The arrangement involves producing multiple copies of the ID molecules and distributing them at strategic locations at selected sets of synapses, then reaching them through small noncoding RNA molecules. This requires the quick creation of entropy-rich messengers and matching receptors, and it suggests that these are created from each other by small-scale transcription and reverse transcription.

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NMDA spikes enhance action potential generation during sensory input

Cited by 272 publications

References 51 publications

On the functions, mechanisms, and malfunctions of intracortical contextual modulation

On the functions, mechanisms, and malfunctions of intracortical contextual modulation

The Role of Dendritic Signaling in the Anesthetic Suppression of Consciousness

Synaptic and extrasynaptic traces of long-term memory: the ID molecule theory

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