Locally sequential synaptic reactivation during hippocampal ripples

The sequential reactivation of memory-relevant neuronal ensembles during hippocampal sharp-wave (SW) ripple oscillations reflects cognitive processing. However, how a downstream neuron decodes this spatiotemporally organized activity remains unexplored. Using subcellular calcium imaging from CA1 pyramidal neurons in ex vivo hippocampal networks, we discovered that neighboring spines are activated serially along dendrites toward or away from cell bodies. Sequential spine activity was engaged repeatedly in different SWs in a complex manner. In a single SW event, multiple sequences appeared discretely in dendritic trees, but overall, sequences occurred preferentially in some dendritic branches. Thus, sequential replays of multineuronal spikes are distributed across several compartmentalized dendritic foci of a postsynaptic neuron, with their spatiotemporal features preserved.

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Long-term stability of cortical ensembles

eLife ◽

10.7554/elife.64449 ◽

2021 ◽

Vol 10 ◽

Author(s):

Jesús Pérez-Ortega ◽

Tzitzitlini Alejandre-García ◽

Rafael Yuste

Keyword(s):

Calcium Imaging ◽

Pyramidal Neurons ◽

Evoked Responses ◽

Single Session ◽

Long Term Stability ◽

Neuronal Ensembles ◽

Two Photon ◽

Layer 2 ◽

Over Time

Neuronal ensembles, coactive groups of neurons found in spontaneous and evoked cortical activity, are causally related to memories and perception, but it still unknown how stable or flexible they are over time. We used two-photon multiplane calcium imaging to track over weeks the activity of the same pyramidal neurons in layer 2/3 of the visual cortex from awake mice and recorded their spontaneous and visually evoked responses. Less than half of the neurons were commonly active across any two imaging sessions. These 'common neurons' formed stable ensembles lasting weeks, but some ensembles were also transient and appeared only in one single session. Stable ensembles preserved ~68 % of their neurons up to 46 days, our longest imaged period, and these 'core' cells had stronger functional connectivity. Our results demonstrate that neuronal ensembles can last for weeks and could, in principle, serve as a substrate for long-lasting representation of perceptual states or memories.

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Co-allocation to overlapping dendritic branches in the retrosplenial cortex integrates contextual memories across time

10.1101/2021.10.28.466343 ◽

2021 ◽

Author(s):

Megha Sehgal ◽

Daniel Almeida-Filho ◽

Sunaina Martin ◽

Irene Davila Mejia ◽

George Kastellakis ◽

...

Keyword(s):

Calcium Imaging ◽

Neuronal Excitability ◽

Retrosplenial Cortex ◽

Causal Role ◽

Contextual Memory ◽

Neuronal Ensembles ◽

Two Photon ◽

Dendritic Plasticity ◽

Dendritic Branches

Events occurring close in time are often linked in memory, providing an episodic timeline and a framework for those memories. Recent studies suggest that memories acquired close in time are encoded by overlapping neuronal ensembles, and that this overlap is necessary for memory linking. Transient increases in neuronal excitability drive this ensemble overlap, but whether dendritic plasticity plays a role in linking memories is unknown. Here, we show that contextual memory linking is not only dependent on ensemble overlap in the retrosplenial cortex (RSC), but also on RSC branch-specific dendritic allocation mechanisms. Using longitudinal two-photon calcium imaging of RSC dendrites, we show that the same dendritic segments are preferentially activated by two linked (but not independent) contextual memories, and that spine clusters added after each of two linked (but not independent) contextual memories are allocated to the same dendritic segments. Importantly, with a novel optogenetic tool, selectively targeted to activated dendritic segments following learning, we show that reactivation of dendrites tagged during the first context exploration is sufficient to link two contextual memories. These results demonstrate a causal role for dendritic mechanisms in memory linking and reveal a novel set of rules that govern how linked, and independent memories are allocated to dendritic compartments.

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SCALING BEHAVIOR OF THE DENDRITIC BRANCHES OF THALAMIC NEURONS

Fractals ◽

10.1142/s0218348x93000186 ◽

1993 ◽

Vol 01 (02) ◽

pp. 171-178 ◽

Cited By ~ 10

Author(s):

KLAUS-D. KNIFFKI ◽

MATTHIAS PAWLAK ◽

CHRISTIANE VAHLE-HINZ

Keyword(s):

Growth Process ◽

Scaling Law ◽

Branching Ratio ◽

Scaling Behavior ◽

Neuronal Growth ◽

Thalamic Neurons ◽

Dendritic Trees ◽

Ventrobasal Complex ◽

Dendritic Branches

The morphology of Golgi-impregnated thalamic neurons was investigated quantitatively. In particular, it was sought to test whether the dendritic bifurcations can be described by the scaling law (d0)n=(d1)n+(d2)nwith a single value of the diameter exponent n. Here d0 is the diameter of the parent branch, d1 and d2 are the diameters of the two daughter branches. Neurons from two functionally distinct regions were compared: the somatosensory ventrobasal complex (VB) and its nociceptive ventral periphery (VBvp). It is shown that for the neuronal trees studied in both regions, the scaling law was fulfilled. The diameter exponent n, however, was not a constant. It increased from n=1.76 for the 1st order branches to n=3.92 for the 7th order branches of neurons from both regions. These findings suggest that more than one simple intrinsic rule is involved in the neuronal growth process, and it is assumed that the branching ratio d0/d1 is not required to be encoded genetically. Furthermore, the results support the concept of the dendritic trees having a statistically identical topology in neurons of VB and VBvp and thus may be regarded as integrative modules.

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Mouse Corticospinal System Comprises Different Functional Neuronal Ensembles Depending On Their Hodology

10.21203/rs.2.10990/v2 ◽

2019 ◽

Author(s):

Rafael Olivares-Moreno ◽

Mónica López-Hidalgo ◽

Alain Altamirano-Espinoza ◽

Adriana González-Gallardo ◽

Anaid Antaramian ◽

...

Keyword(s):

Spinal Cord ◽

Pyramidal Neurons ◽

Functional Organization ◽

Modular Organization ◽

Subcortical Structures ◽

Neuronal Ensembles ◽

Synaptic Interactions ◽

Spinal Cord Segment ◽

Different Populations ◽

Cortex Slices

Abstract Background: Movement performance depends on the synaptic interactions generated by coherent parallel sensorimotor cortical outputs to different downstream targets. The major outputs of the neocortex to subcortical structures are driven by pyramidal tract neurons (PTNs) located in layer 5B. One of the main targets of PTNs is the spinal cord through the corticospinal (CS) system, which is formed by a complex collection of distinct CS circuits. However, little is known about intracortical synaptic interactions that originate CS commands and how different populations of CS neurons are functionally organized. To further understand the functional organization of the CS system, we analyzed the activity of unambiguously identified CS neurons projecting to different zones of the same spinal cord segment using two-photon calcium imaging and retrograde neuronal tracers. Results: Sensorimotor cortex slices obtained from transgenic mice expressing GCaMP6 funder the Thy1 promoter were used to analyze the spontaneous calcium transients in layer 5 pyramidal neurons. Distinct subgroups of CS neurons projecting to dorsal horn and ventral areas of the same segment show more synchronous activity between them than with other subgroups. Conclusions: The results indicate that CS neurons projecting to different spinal cord zones segregated into functional ensembles depending on their hodology, suggesting that a modular organization of CS outputs controls sensorimotor behaviors in a coordinated manner.

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Seizures start as silent microseizures by neuronal ensembles

10.1101/358903 ◽

2018 ◽

Author(s):

Michael Wenzel ◽

Jordan P. Hamm ◽

Darcy S. Peterka ◽

Rafael MD Yuste

Keyword(s):

Calcium Imaging ◽

Travelling Wave ◽

Inhibitory Neurons ◽

Neural Activation ◽

Calcium Dynamics ◽

Neuronal Ensembles ◽

Two Photon ◽

Step Model

AbstractUnderstanding seizure formation and spread remains a critical goal of epilepsy research. While many studies have documented seizure spread, it remains mysterious how they start. We used fast in-vivo two-photon calcium imaging to reconstruct, at cellular resolution, the dynamics of focal cortical seizures as they emerge in epileptic foci (intrafocal), and subsequently propagate (extrafocal). We find that seizures start as intrafocal coactivation of small numbers of neurons (ensembles), which are electrographically silent. These silent “microseizures” expand saltatorily until they break into neighboring cortex, where they progress smoothly and first become detectable by LFP. Surprisingly, we find spatially heterogeneous calcium dynamics of local PV interneuron sub-populations, which rules out a simple role of inhibitory neurons during seizures. We propose a two-step model for the circuit mechanisms of focal seizures, where neuronal ensembles first generate a silent microseizure, followed by widespread neural activation in a travelling wave, which is then detected electrophysiologically.

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Non-synaptic Cell-Autonomous Mechanisms Underlie Neuronal Hyperactivity in a Genetic Model of PIK3CA-Driven Intractable Epilepsy

Frontiers in Molecular Neuroscience ◽

10.3389/fnmol.2021.772847 ◽

2021 ◽

Vol 14 ◽

Author(s):

Achira Roy ◽

Victor Z. Han ◽

Angela M. Bard ◽

Devin T. Wehle ◽

Stephen E. P. Smith ◽

...

Keyword(s):

Neuronal Excitability ◽

Pyramidal Neurons ◽

Genetic Model ◽

Ex Vivo ◽

Significant Proportion ◽

Intractable Epilepsy ◽

Therapeutic Interventions ◽

Hippocampal Pyramidal Neurons ◽

Phosphoinositide 3 Kinase

Patients harboring mutations in the PI3K-AKT-MTOR pathway-encoding genes often develop a spectrum of neurodevelopmental disorders including epilepsy. A significant proportion remains unresponsive to conventional anti-seizure medications. Understanding mutation-specific pathophysiology is thus critical for molecularly targeted therapies. We previously determined that mouse models expressing a patient-related activating mutation in PIK3CA, encoding the p110α catalytic subunit of phosphoinositide-3-kinase (PI3K), are epileptic and acutely treatable by PI3K inhibition, irrespective of dysmorphology. Here we report the physiological mechanisms underlying this dysregulated neuronal excitability. In vivo, we demonstrate epileptiform events in the Pik3ca mutant hippocampus. By ex vivo analyses, we show that Pik3ca-driven hyperactivation of hippocampal pyramidal neurons is mediated by changes in multiple non-synaptic, cell-intrinsic properties. Finally, we report that acute inhibition of PI3K or AKT, but not MTOR activity, suppresses the intrinsic hyperactivity of the mutant neurons. These acute mechanisms are distinct from those causing neuronal hyperactivity in other AKT-MTOR epileptic models and define parameters to facilitate the development of new molecularly rational therapeutic interventions for intractable epilepsy.

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Comparing basal dendrite branches in human and mouse hippocampal CA1 pyramidal neurons with Bayesian networks

Scientific Reports ◽

10.1038/s41598-020-73617-9 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Bojan Mihaljević ◽

Pedro Larrañaga ◽

Ruth Benavides-Piccione ◽

Javier DeFelipe ◽

Concha Bielza

Keyword(s):

Bayesian Networks ◽

Pyramidal Neurons ◽

Graphical Representation ◽

Data Set ◽

Ca1 Region ◽

Basal Dendrites ◽

Hippocampal Ca1 ◽

Dendritic Branches ◽

Branch Type ◽

Human And Mouse

Abstract Pyramidal neurons are the most common cell type in the cerebral cortex. Understanding how they differ between species is a key challenge in neuroscience. A recent study provided a unique set of human and mouse pyramidal neurons of the CA1 region of the hippocampus, and used it to compare the morphology of apical and basal dendritic branches of the two species. The study found inter-species differences in the magnitude of the morphometrics and similarities regarding their variation with respect to morphological determinants such as branch type and branch order. We use the same data set to perform additional comparisons of basal dendrites. In order to isolate the heterogeneity due to intrinsic differences between species from the heterogeneity due to differences in morphological determinants, we fit multivariate models over the morphometrics and the determinants. In particular, we use conditional linear Gaussian Bayesian networks, which provide a concise graphical representation of the independencies and correlations among the variables. We also extend the previous study by considering additional morphometrics and by formally testing whether a morphometric increases or decreases with the distance from the soma. This study introduces a multivariate methodology for inter-species comparison of morphology.

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Dendritic right/left asymmetries in the neurons of the human hippocampal formation: a quantitative Golgi study

Arquivos de Neuro-Psiquiatria ◽

10.1590/s0004-282x2007000700003 ◽

2007 ◽

Vol 65 (4b) ◽

pp. 1105-1113 ◽

Cited By ~ 5

Author(s):

Maria José Sá ◽

Carlos Ruela ◽

Maria Dulce Madeira

Keyword(s):

Pyramidal Neurons ◽

Right Hemisphere ◽

Granule Cells ◽

Hippocampal Formation ◽

Molecular Layer ◽

Pyramidal Cells ◽

Volumetric Analysis ◽

Golgi Study ◽

Dendritic Trees ◽

The Right

OBJECTIVE: To search for right/left asymmetries in the dendritic trees of the neuronal populations and in the cell-free layer volumes of the human hipoccampal formation. METHOD: In necropsic material obtained from six male individuals we performed a quantitative Golgi study of the dendritic trees of dentate granules, CA3 and CA1 pyramidal neurons and a volumetric analysis of dentate gyrus molecular layer, strata oriens plus alveus and strata lacunosum-moleculare plus radiatum of CA3 and CA1 fields. RESULTS: We found inter-hemispheric asymmetries in the dendrites trees of all neurons, reaching the significant level in the number of granule cells dendritic segments (higher in the left than in the right hemisphere), dendritic branching density of CA3 pyramidal cells and mean dendritic length of CA1 apical terminal segments (higher in the right than in the opposite side). No volumetric differences were observed. CONCLUSION: This study points to different anatomical patterns of connectivity in the hippocampal formations of both hemispheres which may underlie functional asymmetries.

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A Simple Method for Establishing AdherentEx VivoExplant Cultures from Human Eye Pathologies for Use in Subsequent Calcium Imaging and Inflammatory Studies

Journal of Immunology Research ◽

10.1155/2014/232659 ◽

2014 ◽

Vol 2014 ◽

pp. 1-10 ◽

Cited By ~ 9

Author(s):

Sofija Andjelic ◽

Xhevat Lumi ◽

Zoltán Veréb ◽

Natasha Josifovska ◽

Andrea Facskó ◽

...

Keyword(s):

Calcium Imaging ◽

Cultured Cells ◽

Cell Attachment ◽

Ex Vivo ◽

Lens Epithelial Cells ◽

Simple Method ◽

Epiretinal Membranes ◽

Anterior Lens Capsule ◽

Reproducible Method ◽

Human Eyes

A novel, simple, and reproducible method for cultivating pathological tissues obtained from human eyes during surgery was developed using viscoelastic material as a tissue adherent to facilitate cell attachment and expansion and calcium imaging of cultured cells challenged by mechanical and acetylcholine (ACh) stimulation as well as inflammatory studies. Anterior lens capsule-lens epithelial cells (aLC-LECs) from cataract surgery and proliferative diabetic retinopathy (PDR) fibrovascular epiretinal membranes (fvERMs) from human eyes were used in the study. We hereby show calcium signaling in aLC-LECs by mechanical and acetylcholine (ACh) stimulation and indicate presence of ACh receptors in these cells. Furthermore, anex vivostudy model was established for measuring the inflammatory response in fvERMs and aLC-LECs upon TNFα treatment.

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Hippocampal hub neurons maintain distinct connectivity throughout their lifetime

Nature Communications ◽

10.1038/s41467-020-18432-6 ◽

2020 ◽

Vol 11 (1) ◽

Cited By ~ 2

Author(s):

Marco Bocchio ◽

Claire Gouny ◽

David Angulo-Garcia ◽

Tom Toulat ◽

Thomas Tressard ◽

...

Keyword(s):

Functional Connectivity ◽

Long Range ◽

Calcium Imaging ◽

Ex Vivo ◽

Adult Brain ◽

Cell Assemblies ◽

Population Synchrony ◽

Neurochemical Analysis ◽

In Vivo Calcium Imaging

Abstract The temporal embryonic origins of cortical GABA neurons are critical for their specialization. In the neonatal hippocampus, GABA cells born the earliest (ebGABAs) operate as ‘hubs’ by orchestrating population synchrony. However, their adult fate remains largely unknown. To fill this gap, we have examined CA1 ebGABAs using a combination of electrophysiology, neurochemical analysis, optogenetic connectivity mapping as well as ex vivo and in vivo calcium imaging. We show that CA1 ebGABAs not only operate as hubs during development, but also maintain distinct morpho-physiological and connectivity profiles, including a bias for long-range targets and local excitatory inputs. In vivo, ebGABAs are activated during locomotion, correlate with CA1 cell assemblies and display high functional connectivity. Hence, ebGABAs are specified from birth to ensure unique functions throughout their lifetime. In the adult brain, this may take the form of a long-range hub role through the coordination of cell assemblies across distant regions.

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