Network instability dynamics drive a transient bursting period in the developing hippocampus in vivo

Spontaneous correlated activity is a universal hallmark of immature neural circuits. However, the cellular dynamics and intrinsic mechanisms underlying neuronal synchrony in the intact developing brain are largely unknown. Here, we use two-photon Ca2+ imaging to comprehensively map the developmental trajectories of spontaneous network activity in hippocampal area CA1 in vivo. We unexpectedly find that synchronized activity peaks after the developmental emergence of effective synaptic inhibition in the second postnatal week. We demonstrate that the enhanced network synchrony reflects an increased functional coupling of individual neurons to local population activity. However, pairwise neuronal correlations are low, and network bursts recruit CA1 pyramidal cells in a virtually random manner. Using a dynamic systems modeling approach, we reconcile these experimental findings and identify network bi-stability as a potential regime underlying network burstiness at this age. Our analyses reveal an important role of synaptic input characteristics and network instability dynamics for the emergence of neuronal synchrony. Collectively, our data suggest a mechanism, whereby developing CA1 performs extensive input-discrimination learning prior to the onset of environmental exploration.

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Homeostatic plasticity rules control the wiring of axo-axonic synapses at the axon initial segment

10.1101/453753 ◽

2018 ◽

Cited By ~ 1

Author(s):

Alejandro Pan-Vazquez ◽

Winnie Wefelmeyer ◽

Victoria Gonzalez Sabater ◽

Juan Burrone

Keyword(s):

Initial Segment ◽

Pyramidal Cells ◽

Axon Initial Segment ◽

Homeostatic Plasticity ◽

Network Activity ◽

Gabaergic Interneuron ◽

Chandelier Cells ◽

Local Circuits ◽

And Function

AbstractGABAergic interneurons are chiefly responsible for controlling the activity of local circuits in the cortex1,2. However, the rules that govern the wiring of interneurons are not well understood3. Chandelier cells (ChCs) are a type of GABAergic interneuron that control the output of hundreds of neighbouring pyramidal cells through axo-axonic synapses which target the axon initial segment (AIS)4. Despite their importance in modulating circuit activity, our knowledge of the development and function of axo-axonic synapses remains elusive. In this study, we investigated the role of activity in the formation and plasticity of ChC synapses. In vivo imaging of ChCs during development uncovered a narrow window (P12-P18) over which axons arborized and formed connections. We found that increases in the activity of either pyramidal cells or individual ChCs during this temporal window resulted in a reversible decrease in axo-axonic connections. Voltage imaging of GABAergic transmission at the AIS showed that axo-axonic synapses were depolarising during this period. Identical manipulations of network activity in older mice (P40-P46), when ChC synapses are inhibitory, resulted in an increase in axo-axonic synapses. We propose that the direction of ChC plasticity follows homeostatic rules that depend on the polarity of axo-axonic synapses.

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A Method to Estimate Synaptic Conductances From Membrane Potential Fluctuations

Journal of Neurophysiology ◽

10.1152/jn.01223.2003 ◽

2004 ◽

Vol 91 (6) ◽

pp. 2884-2896 ◽

Cited By ~ 79

Author(s):

Michael Rudolph ◽

Zuzanna Piwkowska ◽

Mathilde Badoual ◽

Thierry Bal ◽

Alain Destexhe

Keyword(s):

Membrane Potential ◽

Computational Models ◽

Network Activity ◽

Intracellular Recordings ◽

Neocortical Neurons ◽

Underlying Network ◽

Analytic Expression ◽

Synaptic Conductances

In neocortical neurons, network activity can activate a large number of synaptic inputs, resulting in highly irregular subthreshold membrane potential ( Vm) fluctuations, commonly called “synaptic noise.” This activity contains information about the underlying network dynamics, but it is not easy to extract network properties from such complex and irregular activity. Here, we propose a method to estimate properties of network activity from intracellular recordings and test this method using theoretical and experimental approaches. The method is based on the analytic expression of the subthreshold Vm distribution at steady state in conductance-based models. Fitting this analytic expression to Vm distributions obtained from intracellular recordings provides estimates of the mean and variance of excitatory and inhibitory conductances. We test the accuracy of these estimates against computational models of increasing complexity. We also test the method using dynamic-clamp recordings of neocortical neurons in vitro. By using an on-line analysis procedure, we show that the measured conductances from spontaneous network activity can be used to re-create artificial states equivalent to real network activity. This approach should be applicable to intracellular recordings during different network states in vivo, providing a characterization of the global properties of synaptic conductances and possible insight into the underlying network mechanisms.

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Regional heterogeneity of developing GABAergic interneuron excitation in vivo

10.1101/701862 ◽

2019 ◽

Cited By ~ 1

Author(s):

Yasunobu Murata ◽

Matthew T. Colonnese

Keyword(s):

Synapse Formation ◽

Critical Role ◽

Reversal Potential ◽

Pyramidal Cells ◽

Gabaergic Neurons ◽

Network Activity ◽

Gabaergic Interneuron ◽

Intact Brain

AbstractGABAergic interneurons are proposed to be critical for early activity and synapse formation by directly exciting, rather than inhibiting, neurons in developing hippocampus and neocortex. However, the role of GABAergic neurons in the generation of neonatal network activity has not been tested in vivo, and recent studies have challenged the excitatory nature of early GABA. By locally manipulating interneuron activity in unanesthetized neonatal mice, we show that GABAergic neurons are indeed excitatory in hippocampus at postnatal-day 3 (P3), and responsible for most of the spontaneous firing of pyramidal cells at that age. Hippocampal interneurons become inhibitory by P7, whereas cortical interneurons are inhibitory at P3 and remain so throughout development. This regional and age heterogeneity is the result of a change in chloride reversal potential as activation of light-gated anion channels expressed in glutamatergic neurons causes firing in hippocampus at P3, but silences it at P7. This study in the intact brain reveals a critical role for GABAergic interneuron excitation in neonatal hippocampus, and a surprising heterogeneity of interneuron function in cortical circuits that was not predicted from in vitro studies.

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Consequences of human Tau aggregation in the hippocampal formation of ageing mice in vivo

10.1101/2021.11.24.469849 ◽

2021 ◽

Author(s):

Tim J Viney ◽

Barbara Sarkany ◽

A Tugrul Ozdemir ◽

Katja Hartwich ◽

Judith Schweimer ◽

...

Keyword(s):

Transgenic Mice ◽

Pyramidal Neurons ◽

Hippocampal Formation ◽

Pyramidal Cells ◽

Reference Memory ◽

Network Activity ◽

Motor Impairments ◽

Tau Aggregation ◽

High Firing

Intracellular aggregation of hyperphosphorylated Tau (pTau) in the brain is associated with cognitive and motor impairments, and ultimately neurodegeneration. We investigate how human pTau affects cells and network activity in the hippocampal formation of THY-Tau22 tauopathy model mice in vivo. We find that pTau preferentially accumulates in deep-layer pyramidal neurons, leading to neurodegeneration, and we establish that pTau spreads to oligodendrocytes. During goal-directed virtual navigation in aged transgenic mice, we detect fewer high-firing pyramidal cells, with the remaining cells retaining their coupling to theta oscillations. Analysis of network oscillations and firing patterns of pyramidal and GABAergic neurons recorded in head-fixed and freely-moving mice suggests preserved neuronal coordination. In spatial memory tests, transgenic mice have reduced short-term familiarity but spatial working and reference memory are surprisingly normal. We hypothesize that unimpaired subcortical network mechanisms implementing cortical neuronal coordination compensate for the widespread pTau aggregation, loss of high-firing cells and neurodegeneration.

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GABAergic interneurons excite neonatal hippocampus in vivo

Science Advances ◽

10.1126/sciadv.aba1430 ◽

2020 ◽

Vol 6 (24) ◽

pp. eaba1430 ◽

Cited By ~ 5

Author(s):

Yasunobu Murata ◽

Matthew T. Colonnese

Keyword(s):

Visual Cortex ◽

Synapse Formation ◽

Reversal Potential ◽

Pyramidal Cells ◽

Gabaergic Neurons ◽

Network Activity ◽

Gabaergic Interneuron ◽

Gabaergic Interneurons ◽

Early Postnatal Development

GABAergic interneurons are proposed to be critical for early activity and synapse formation by directly exciting, rather than inhibiting, neurons in developing hippocampus and neocortex. However, the role of GABAergic neurons in the generation of neonatal network activity has not been tested in vivo, and recent studies have challenged the excitatory nature of early GABA. By locally manipulating interneuron activity in unanesthetized neonatal mice, we show that GABAergic neurons are excitatory in CA1 hippocampus at postnatal day 3 (P3) and are responsible for most of the spontaneous firing of pyramidal cells at that age. Hippocampal interneurons become inhibitory by P7, whereas visual cortex interneurons are already inhibitory by P3 and remain so throughout development. These regional and age-specific differences are the result of a change in chloride reversal potential, because direct activation of light-gated anion channels in glutamatergic neurons drives CA1 firing at P3, but silences it at P7 in CA1, and at all ages in visual cortex. This study in the intact brain reveals that GABAergic interneuron excitation is essential for network activity in neonatal hippocampus and confirms that visual cortical interneurons are inhibitory throughout early postnatal development.

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Tolfenamic Acid Prevents Amyloid β-induced Olfactory Bulb Dysfunction In Vivo

Current Alzheimer Research ◽

10.2174/1567205015666180223091233 ◽

2018 ◽

Vol 15 (8) ◽

pp. 731-742 ◽

Cited By ~ 4

Author(s):

José M. Cornejo-Montes-de-Oca ◽

Rebeca Hernández-Soto ◽

Arturo G. Isla ◽

Carlos E. Morado-Urbina ◽

Fernando Peña-Ortega

Keyword(s):

Olfactory Bulb ◽

Amyloid Beta ◽

Amyloid Β ◽

Tolfenamic Acid ◽

Network Activity ◽

Protective Effects ◽

Population Activity ◽

Activity Inhibition

Background: Amyloid beta inhibits olfactory bulb function. The mechanisms involved in this effect must include alterations in network excitability, inflammation and the activation of different transduction pathways. Thus, here we tested whether tolfenamic acid, a drug that modulates several of these pathological processes, could prevent amyloid beta-induced olfactory bulb dysfunction. Objective: To test whether tolfenamic acid prevents amyloid beta-induced alterations in olfactory bulb network function, olfaction and GSK3β activity. Method: The protective effects of tolfenamic acid against amyloid beta-induced population activity inhibition were tested in olfactory bulb slices from adult mice, while tolfenamic acid and amyloid beta were bath-applied. We also tested the effects of amyloid-beta in slices obtained from animals pre-treated chronically (21 days) with tolfenamic acid. The effects of amyloid beta micro-injected into the olfactory bulbs were also tested, after two weeks, on olfactory bulb population activity and olfaction in control and tolfenamic acid chronically treated animals. Olfaction was assessed with the odor-avoidance and the habituation/cross-habituation tests. GSK3β activation was evaluated with Western-blot. Results: Acute bath application of tolfenamic acid does not prevent amyloid beta-induced inhibition of olfactory bulb network activity in vitro. In contrast, chronic treatment with tolfenamic acid renders the olfactory bulb resistant to amyloid beta-induced network activity inhibition in vitro and in vivo, which correlates with the inhibition of GSK3β activation and the protection against amyloid beta-induced olfactory dysfunction. Conclusion: Our data further support the use of tolfenamic acid to prevent amyloid beta-induced pathology and the early symptoms of Alzheimer Disease.

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Intrinsic and Synaptic Mechanisms Determining the Timing of Neuron Population Activity During Hippocampal Theta Oscillation

Journal of Neurophysiology ◽

10.1152/jn.01233.2005 ◽

2006 ◽

Vol 96 (6) ◽

pp. 2889-2904 ◽

Cited By ~ 31

Author(s):

Gergő Orbán ◽

Tamás Kiss ◽

Péter Érdi

Keyword(s):

Metabotropic Glutamate Receptors ◽

Pyramidal Cells ◽

Neuron Population ◽

Population Activity ◽

Theta Oscillation ◽

Hippocampal Ca1 ◽

Theta Frequency ◽

Hippocampal Theta

Hippocampal theta (3–8 Hz) is a major electrophysiological activity in rodents, which can be found in primates and humans as well. During theta activity, pyramidal cells and different classes of interneurons were shown to discharge at different phases of the extracellular theta. A recent in vitro study has shown that theta-frequency oscillation can be elicited in a hippocampal CA1 slice by the activation of metabotropic glutamate receptors with similar pharmacological and physiological profile that was found in vivo. We constructed a conductance based three-population network model of the hippocampal CA1 region to study the specific roles of neuron types in the generation of the in vitro theta oscillation and the emergent network properties. Interactions between pairs of neuron populations were studied systematically to assess synchronization and delay properties. We showed that the circuitry consisting of pyramidal cells and two types of hippocampal interneurons [basket and oriens lacunosum-moleculare (O-LM) neurons] was able to generate coherent theta-frequency population oscillation. Furthermore, we found that hyperpolarization-activated nonspecific cation current in pyramidal cells, but not in O-LM neurons, plays an important role in the timing of spike generation, and thus synchronization of pyramidal cells. The model was shown to exhibit the same phase differences between neuron population activities found in vivo, supporting the idea that these patterns of activity are determined internal to the hippocampus.

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Hyperthermia Modulates Respiratory Pacemaker Bursting Properties

Journal of Neurophysiology ◽

10.1152/jn.00752.2003 ◽

2004 ◽

Vol 92 (5) ◽

pp. 2844-2852 ◽

Cited By ~ 35

Author(s):

Andrew K. Tryba ◽

Jan-Marino Ramirez

Keyword(s):

Network Effects ◽

Elevated Temperatures ◽

Heat Stroke ◽

Network Activity ◽

Respiratory Neurons ◽

Population Activity ◽

Normal Body Temperature ◽

Respiratory Network ◽

Hyperthermic Response

Most mammals modulate respiratory frequency (RF) to dissipate heat (e.g., panting) and avoid heat stroke during hyperthermic conditions. Respiratory neural network activity recorded in an isolated brain stem-slice preparation of mice exhibits a similar RF modulation in response to hyperthermia; fictive eupneic frequency increases while inspiratory network activity amplitude and duration are significantly reduced. Here, we study the effects of hyperthermia on the activity of synaptically isolated respiratory pacemakers to examine the possibility that these changes may account for the hyperthermic RF modulation of the respiratory network. During heating, modulation of the bursting frequency of synaptically isolated pacemakers paralleled that of population bursting recorded from the intact network, whereas nonpacemaker neurons were unaffected, suggesting that pacemaker bursting may account for the temperature-enhanced RF observed at the network level. Some respiratory neurons that were tonically active at hypothermic conditions exhibited pacemaker properties at approximately the normal body temperature of eutherian mammals (36.81 ± 1.17°C; mean ± SD) and continued to burst at 40°C. At elevated temperatures (40°C), there was an enhancement of the depolarizing drive potential in synaptically isolated pacemakers, while the amplitude of integrated population activity declined. Isolated pacemaker bursting ceased at 41–42°C ( n = 5), which corresponds to temperatures at which hyperthermic-apnea typically occurs in vivo. We conclude that pacemaker properties may play an important role in the hyperthermic frequency modulation and apnea, while network effects may play important roles in generating other aspects of the hyperthermic response, such as the decreased amplitude of ventral respiratory group activity during hyperthermia.

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An in vivo Calcium Imaging Approach for the Identification of Cell-Type Specific Patterns in the Developing Cortex

Frontiers in Neural Circuits ◽

10.3389/fncir.2021.747724 ◽

2021 ◽

Vol 15 ◽

Author(s):

Alicia Che ◽

Natalia V. De Marco García

Keyword(s):

Neuronal Activity ◽

Neural Development ◽

Activity Patterns ◽

Pyramidal Cells ◽

Network Activity ◽

Neuronal Diversity ◽

Neuronal Populations ◽

Cranial Window ◽

Developing Neurons

Neuronal activity profoundly shapes the maturation of developing neurons. However, technical limitations have hampered the ability to capture the progression of activity patterns in genetically defined neuronal populations. This task is particularly daunting given the substantial diversity of pyramidal cells and interneurons in the neocortex. A hallmark in the development of this neuronal diversity is the participation in network activity that regulates circuit assembly. Here, we describe detailed methodology on imaging neuronal cohorts longitudinally throughout postnatal stages in the mouse somatosensory cortex. To capture neuronal activity, we expressed the genetically encoded calcium sensor GCaMP6s in three distinct interneuron populations, the 5HT3aR-expressing layer 1 (L1) interneurons, SST interneurons, and VIP interneurons. We performed cranial window surgeries as early as postnatal day (P) 5 and imaged the same cohort of neurons in un-anesthetized mice from P6 to P36. This Longitudinal two-photon imaging preparation allows the activity of single neurons to be tracked throughout development as well as plasticity induced by sensory experience and learning, opening up avenues of research to answer fundamental questions in neural development in vivo.

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OFF-periods reduce the complexity of neocortical activity during sleep

10.1101/2021.06.11.448131 ◽

2021 ◽

Author(s):

Joaquin Gonzalez ◽

Matias Cavelli ◽

Adriano BL Tort ◽

Pablo Torterolo ◽

Nicolás Rubido

Keyword(s):

Rem Sleep ◽

Slow Wave Sleep ◽

Neural Mechanism ◽

Population Activity ◽

Temporal Complexity ◽

Field Recordings ◽

Neuronal Populations ◽

Branching Model ◽

Experimental Findings

Field recordings decrease their temporal complexity during slow-wave sleep (SWS), however, the neural mechanism for this decrease remains elusive. Here, we show that this complexity reduction is caused by synchronous neuronal OFF-periods by analysing in-vivo recordings from neocortical neuronal populations. We find that OFF-periods trap cortical dynamics, disrupting causal interactions and making the population activity more recurrent, deterministic, and less chaotic than during REM sleep or Wakefulness. Moreover, when we exclude OFF-periods, SWS becomes indistinguishable from Wakefulness or REM sleep. In fact, for all states, we show that the spiking activity has a universal scaling compatible with critical phenomena. We complement these results by analysing a critical branching model that replicates the experimental findings, where we show that forcing OFF-periods into a percentage of neurons suffices to generate a decrease in complexity that replicates SWS.

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