La trama interétnica

Losonczy, Anne-Marie

doi:10.4000/books.ifea.4695

Cited by 29 publications

(5 citation statements)

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“…There are two key differences with most other neural models. First, learning is isolated to individual dendritic segments (Stuart and Häusser, 2001;Losonczy et al, 2008). Second, the model neuron learns by growing and removing synapses from a pool of potential synapses (Chklovskii et al, 2004).…”

Section: Learningmentioning

confidence: 99%

Why Does the Neocortex Have Columns, A Theory of Learning the Structure of the World

Hawkins

Ahmad

Cui

2017

Preprint

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Neocortical regions are organized into columns and layers. Connections between layers run mostly perpendicular to the surface suggesting a columnar functional organization. Some layers have long-range excitatory lateral connections suggesting interactions between columns. Similar patterns of connectivity exist in all regions but their exact role remain a mystery. In this paper, we propose a network model composed of columns and layers that performs robust object learning and recognition. Each column integrates its changing input over time to learn complete predictive models of observed objects. Excitatory lateral connections across columns allow the network to more rapidly infer objects based on the partial knowledge of adjacent columns. Because columns integrate input over time and space, the network learns models of complex objects that extend well beyond the receptive field of individual cells. Our network model introduces a new feature to cortical columns. We propose that a representation of location relative to the object being sensed is calculated within the sub-granular layers of each column. The location signal is provided as an input to the network, where it is combined with sensory data. Our model contains two layers and one or more columns. Simulations show that using Hebbian-like learning rules small single-column networks can learn to recognize hundreds of objects, with each object containing tens of features. Multi-column networks recognize objects with significantly fewer movements of the sensory receptors. Given the ubiquity of columnar and laminar connectivity patterns throughout the neocortex, we propose that columns and regions have more powerful recognition and modeling capabilities than previously assumed.

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Section: Learningmentioning

confidence: 99%

Why Does the Neocortex Have Columns, A Theory of Learning the Structure of the World

Hawkins

Ahmad

Cui

2017

Preprint

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“…The activation of ES-NMDARs under physiological conditions is believed to arise from 'spill-over' of synaptic glutamate into the extrasynaptic space during intense synaptic activity (Asztely et al 1997) which is proposed to access receptors within the proximity of the postsynaptic density (around 300 nm) termed perisynaptic NMDARs (see Kohr, 2006;Groc et al 2009). ES-NMDARs located on the dendritic shaft may play a role in the regulation of dendritic excitability and plasticity (Kullmann et al 1996;Clark & Cull-Candy, 2002;Losonczy et al 2008;Wu et al 2012).…”

Section: Introductionmentioning

confidence: 99%

A novel method using ambient glutamate for the electrophysiological quantification of extrasynaptic NMDA receptor function in acute brain slices

Moldavski

Behr

Bading

et al. 2020

The Journal of Physiology

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Key pointsr We present a novel protocol to quantify extrasynaptic NMDA receptor function utilizing the semi-selective activation of extrasynaptic receptors by ambient extracellular glutamate in acute brain slices from adult rats.r We use whole cell patch clamp to measure the effect of the NMDA receptor antagonist MK-801 on both synaptic and brief, local agonist application-evoked responses.r The level of ambient glutamate was estimated from tonic NMDA receptor activity to be ß77 nM and an equivalent concentration of NMDA was used to estimate the degree of extrasynaptic blockade (>82%) by our MK-801 protocol.r The extrasynaptic component of the total NMDA receptor pool can be mathematically derived from these data and was estimated to be 29-39% in the stratum radiatum of the CA1 region of the rat hippocampus.r This technique could be used to quantify extrasynaptic NMDA receptor function in rodent models of diseases where extrasynaptic NMDA receptors are implicated in neuron death.Abstract Synaptic NMDA receptors (NMDARs) play a central role in pro-survival signalling and synaptic plasticity in the majority of excitatory synapses in the central nervous system whereas extrasynaptic NMDARs (ES-NMDARs) activate pro-death pathways and have been implicated in many neurodegenerative diseases. ES-NMDARs have been characterized in acute brain slice preparations using the largely irreversible, activity-dependent NMDAR antagonist MK-801 to block synaptic NMDARs. This approach is limited by the concomitant MK-801 blockade of ES-NMDARs activated by ambient extracellular glutamate, which is largely absent from the synaptic cleft due to the high density of nearby glutamate transporters. In acute hippocampal slices from rats aged 35-42 postnatal days, we estimated ambient glutamate to be 72-83 nM Alexander Moldavski studied medicine at the University of Mainz and performed his research for his MD thesis at the University of Heidelberg, both in Germany. He continued his research in the area of cellular neurophysiology at resulting in a block of more than 82% of ES-NMDARs during a 5 min MK-801 application. This paper describes a novel electrophysiological and mathematical method to quantify the proportion of NMDARs located at extrasynaptic locations in a confined region of an acute brain slice preparation using MK-801 to preferentially block ES-NMDARs. The protocol uses whole cell patch clamp measurement of NMDAR responses to synaptic stimulation and brief local pressure application of NMDA before and after MK-801 application. After mathematically correcting for the relative block of both synaptic and extrasynaptic receptors, ES-NMDARs were estimated to comprise 29-39% of the total NMDAR pool in the apical dendrites of hippocampal CA1 pyramidal neurons. This new method may prove useful for accurate quantification of NMDAR distributions in neurodegenerative diseases that are associated with increased toxic ES-NMDAR signalling.

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“…In neurons, Kv4 channels are thought to regulate the frequency of repetitive firing, the backpropagation of the action potential into the dendritic tree and dendritic integration and plasticity (Hoffman et al 1997;Cai et al 2004;Jerng et al 2004;Magee & Johnston, 2005;. They have recently been implicated in mediating a number of important functions such as the compartmentalized changes in dendritic branch excitability that are important in learning (Losonczy et al 2008) and the differential Ca 2+ elevation in the dendrites of D1 and D2-expressing striatal medium spiny neurons (MSNs) (Day et al 2008). However, it has been difficult to directly demonstrate that the currents responsible for these functions are Kv4-mediated due to the lack of adequate channel blockers specific for these channels.…”

Section: Introductionmentioning

confidence: 99%

Dipeptidyl‐peptidase‐like‐proteins confer high sensitivity to the scorpion toxin AmmTX3 to Kv4‐mediated A‐type K⁺ channels

Maffie

Dvoretskova

Bougis

et al. 2013

The Journal of Physiology

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Key points• AmmTX3, a member of the α-KTX15 family of scorpion toxins, efficiently and specifically blocks the subthreshold-operating A-type K + current in cerebellar granule neurons from wild-type mice but not in neurons from mice lacking the Kv4 channel-associated protein DPP6.• In heterologous cells high-affinity blockade of Kv4.2 and Kv4.3 channels by AmmTX3 requires the presence of the associated proteins DPP6 and DPP10.• These results validate AmmTX3 as a specific blocker of Kv4 channels in CNS neurons and explain the discrepancy between previous observations in neurons and heterologous cells.• They contribute a powerful tool to investigate the physiological role of A-type K + currents, believed to be important in dendritic integration and plasticity and to be involved in a number of diseases.• Our results demonstrate that, in addition to changing the kinetics and voltage dependence of Kv4 channel complexes, DDP-like Kv4-associated proteins also affect their pharmacological profile.Abstract K + channels containing Kv4.2 and Kv4.3 pore-forming subunits mediate most of the subthreshold-operating somatodendritic A-type K + current in CNS neurons. These channels are believed to be important in regulating the frequency of repetitive firing, the backpropagation of action potential into dendrites, and dendritic integration and plasticity. Moreover, they have been implicated in several diseases from pain to epilepsy and autism spectrum disorders. The lack of toxins that specifically and efficiently block these channels has hampered studies aimed at confirming their functional role and their involvement in disease. AmmTX3 and other related members of the α-KTX15 family of scorpion toxins have been shown to block the A-type K + current in cultured neurons, but their specificity has been questioned because the toxins do not efficiently block the currents mediated by Kv4.2 or Kv4.3 subunits expressed in heterologous cells. Here we show that the high-affinity blockade of Kv4.2 and Kv4.3 channels by AmmTX3 depends on the presence of the auxiliary subunits DPP6 and DPP10. These proteins are thought to be components of the Kv4 channel complex in neurons and to be important for channel expression in dendrites. These studies validate the use of AmmTX3 as a blocker of the Kv4-mediated A-type K + current in neurons.

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La trama interétnica

Cited by 29 publications

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Why Does the Neocortex Have Columns, A Theory of Learning the Structure of the World

Why Does the Neocortex Have Columns, A Theory of Learning the Structure of the World

A novel method using ambient glutamate for the electrophysiological quantification of extrasynaptic NMDA receptor function in acute brain slices

Dipeptidyl‐peptidase‐like‐proteins confer high sensitivity to the scorpion toxin AmmTX3 to Kv4‐mediated A‐type K⁺ channels

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La trama interétnica

Cited by 29 publications

References 0 publications

Why Does the Neocortex Have Columns, A Theory of Learning the Structure of the World

Why Does the Neocortex Have Columns, A Theory of Learning the Structure of the World

A novel method using ambient glutamate for the electrophysiological quantification of extrasynaptic NMDA receptor function in acute brain slices

Dipeptidyl‐peptidase‐like‐proteins confer high sensitivity to the scorpion toxin AmmTX3 to Kv4‐mediated A‐type K+ channels

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Dipeptidyl‐peptidase‐like‐proteins confer high sensitivity to the scorpion toxin AmmTX3 to Kv4‐mediated A‐type K⁺ channels