Neuronal Glutamatergic Network Electrically Wired with Silent But Activatable Gap Junctions

Ixmatlahua, Diana J.; Vizcarra, Bianca; Gómez-Lira, Gisela; Romero-Maldonado, Isabel; Ortiz, Franco; Rojas-Piloni, Gerardo; Gutiérrez, Rafael

doi:10.1523/jneurosci.2590-19.2020

Cited by 12 publications

(24 citation statements)

References 37 publications

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“…The involvement of gap junctions in the hippocampal formation is associated with neuronal synchronization during oscillatory activity, mainly between GABAergic parvalbumin-positive interneurons (Ylinen et al, 1995;Fukuda and Kosaka, 2000;Baude et al, 2007). Recent evidence showed that gap junctions are present in the adult hippocampus between glutamatergic cells as mixed synapses but remain mainly closed under control conditions (,10%) and require acidic changes in intracellular pH to increase the opening probability (Ixmatlahua et al, 2020). Additional experimental evidence should be collected to address the role of gap junctions during nonrhythmic activity and for inclusion in circuitry estimates.…”

Section: From Morphology To Function: Synaptic Count and Implications For Local Circuitsmentioning

confidence: 99%

Comprehensive Estimates of Potential Synaptic Connections in Local Circuits of the Rodent Hippocampal Formation by Axonal-Dendritic Overlap

et al. 2020

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A quantitative description of the hippocampal formation synaptic architecture is essential for understanding the neural mechanisms of episodic memory. Yet the existing knowledge of connectivity statistics between different neuron types in the rodent hippocampus only captures a mere 5% of this circuitry. We present a systematic pipeline to produce first-approximation estimates for most of the missing information. Leveraging the www.Hippocampome.org knowledge base, we derive local connection parameters between distinct pairs of morphologically identified neuron types based on their axonal-dendritic overlap within every layer and subregion of the hippocampal formation. Specifically, we adapt modern image analysis technology to determine the parcel-specific neurite lengths of every neuron type from representative morphologic reconstructions obtained from either sex. We then compute the average number of synapses per neuron pair using relevant anatomic volumes from the mouse brain atlas and ultrastructurally established interaction distances. Hence, we estimate connection probabilities and number of contacts for .1900 neuron type pairs, increasing the available quantitative assessments more than 11-fold. Connectivity statistics thus remain unknown for only a minority of potential synapses in the hippocampal formation, including those involving long-range (23%) or perisomatic (6%) connections and neuron types without morphologic tracings (7%). The described approach also yields approximate measurements of synaptic distances from the soma along the dendritic and axonal paths, which may affect signal attenuation and delay. Overall, this dataset fills a substantial gap in quantitatively describing hippocampal circuits and provides useful model specifications for biologically realistic neural network simulations, until further direct experimental data become available.

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Section: From Morphology To Function: Synaptic Count and Implications For Local Circuitsmentioning

confidence: 99%

Comprehensive Estimates of Potential Synaptic Connections in Local Circuits of the Rodent Hippocampal Formation by Axonal-Dendritic Overlap

et al. 2020

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“…Schmitz et al (2001) provided evidence that axons of hippocampal principal cells are electrically coupled, and can represent a mechanism for very fast electrical communication. The idea that principal cells in the hippocampus establish electrical synapses with each other, implicated in network oscillations and synchronization, is further supported by additional recent studies (Molchanova et al 2016;Ixmatlahua et al 2020). Furthermore, recent experiments suggest that the strength of gap junctions can be modified in an activitydependent manner, similar to that of chemical synapses (Cachope et al 2007;Turecek et al 2014;Wang et al 2015).…”

Section: Basic Model Assumptions and Layersmentioning

confidence: 84%

“…A strong candidate can be the presence of gap-junctions. Various authors recently demonstrated the presence of an ultra-fast electrical communication mechanism in the hippocampus, and related it with network oscillations (Schmitz et al 2001 ; Ixmatlahua et al 2020 ).…”

Section: Methodsmentioning

confidence: 99%

A model of working memory for encoding multiple items and ordered sequences exploiting the theta-gamma code

2022

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Recent experimental evidence suggests that oscillatory activity plays a pivotal role in the maintenance of information in working memory, both in rodents and humans. In particular, cross-frequency coupling between theta and gamma oscillations has been suggested as a core mechanism for multi-item memory. The aim of this work is to present an original neural network model, based on oscillating neural masses, to investigate mechanisms at the basis of working memory in different conditions. We show that this model, with different synapse values, can be used to address different problems, such as the reconstruction of an item from partial information, the maintenance of multiple items simultaneously in memory, without any sequential order, and the reconstruction of an ordered sequence starting from an initial cue. The model consists of four interconnected layers; synapses are trained using Hebbian and anti-Hebbian mechanisms, in order to synchronize features in the same items, and desynchronize features in different items. Simulations show that the trained network is able to desynchronize up to nine items without a fixed order using the gamma rhythm. Moreover, the network can replicate a sequence of items using a gamma rhythm nested inside a theta rhythm. The reduction in some parameters, mainly concerning the strength of GABAergic synapses, induce memory alterations which mimic neurological deficits. Finally, the network, isolated from the external environment (“imagination phase”) and stimulated with high uniform noise, can randomly recover sequences previously learned, and link them together by exploiting the similarity among items.

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“…In addition to mefloquine, other unspecific Cx36 blockers, such as quinine or quinidine, inhibit spreading depolarization [63]. In the light of this evidence, we hypothesize that the mechanism of neuroprotection exerted by 2-APB linked with a lower cumulative time of depolarization events can underlie a possible inhibition of Cx36 channels, especially because Cx36 channels are opened by ischemia [64,65] and that the neuroprotection exerted by 2-APB in our study phenocopies the decreased depolarization time observed after ischemia in Cx36-deficient mice [60].…”

Section: Discussionmentioning

confidence: 99%

Postischemic Neuroprotection of Aminoethoxydiphenyl Borate Associates Shortening of Peri-Infarct Depolarizations

Fernández-Serra

Martínez‐Alonso

Alcázar

et al. 2022

IJMS

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Brain stroke is a highly prevalent pathology and a main cause of disability among older adults. If not promptly treated with recanalization therapies, primary and secondary mechanisms of injury contribute to an increase in the lesion, enhancing neurological deficits. Targeting excitotoxicity and oxidative stress are very promising approaches, but only a few compounds have reached the clinic with relatively good positive outcomes. The exploration of novel targets might overcome the lack of clinical translation of previous efficient preclinical neuroprotective treatments. In this study, we examined the neuroprotective properties of 2-aminoethoxydiphenyl borate (2-APB), a molecule that interferes with intracellular calcium dynamics by the antagonization of several channels and receptors. In a permanent model of cerebral ischemia, we showed that 2-APB reduces the extent of the damage and preserves the functionality of the cortical territory, as evaluated by somatosensory evoked potentials (SSEPs). While in this permanent ischemia model, the neuroprotective effect exerted by the antioxidant scavenger cholesteronitrone F2 was associated with a reduction in reactive oxygen species (ROS) and better neuronal survival in the penumbra, 2-APB did not modify the inflammatory response or decrease the content of ROS and was mostly associated with a shortening of peri-infarct depolarizations, which translated into better cerebral blood perfusion in the penumbra. Our study highlights the potential of 2-APB to target spreading depolarization events and their associated inverse hemodynamic changes, which mainly contribute to extension of the area of lesion in cerebrovascular pathologies.

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Neuronal Glutamatergic Network Electrically Wired with Silent But Activatable Gap Junctions

Cited by 12 publications

References 37 publications

Comprehensive Estimates of Potential Synaptic Connections in Local Circuits of the Rodent Hippocampal Formation by Axonal-Dendritic Overlap

Comprehensive Estimates of Potential Synaptic Connections in Local Circuits of the Rodent Hippocampal Formation by Axonal-Dendritic Overlap

A model of working memory for encoding multiple items and ordered sequences exploiting the theta-gamma code

Postischemic Neuroprotection of Aminoethoxydiphenyl Borate Associates Shortening of Peri-Infarct Depolarizations

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