β-Adrenergic modulation of spontaneous spatiotemporal activity patterns and synchrony in hyperexcitable hippocampal circuits

2012 ◽  
Vol 108 (2) ◽  
pp. 658-671 ◽  
Author(s):  
Anupam Hazra ◽  
Robert Rosenbaum ◽  
Bernhard Bodmann ◽  
Siyuan Cao ◽  
Krešimir Josić ◽  
...  
Keyword(s):  
Propagation Velocity ◽  
Activity Patterns ◽  
Pyramidal Cells ◽  
Network Activity ◽  
Neural Activation ◽  
Ca1 Pyramidal Cells ◽  
Spatiotemporal Characteristics ◽  
Adrenergic Modulation ◽  
Whole Cell Recordings

A description of healthy and pathological brain dynamics requires an understanding of spatiotemporal patterns of neural activity and characteristics of its propagation between interconnected circuits. However, the structure and modulation of the neural activation maps underlying these patterns and their propagation remain elusive. We investigated effects of β-adrenergic receptor (β-AR) stimulation on the spatiotemporal characteristics of emergent activity in rat hippocampal circuits. Synchronized epileptiform-like activity, such as interictal bursts (IBs) and ictal-like events (ILEs), were evoked by 4-aminopyridine (4-AP), and their dynamics were studied using a combination of electrophysiology and fast voltage-sensitive dye imaging. Dynamic characterization of the spontaneous IBs showed that they originated in dentate gyrus/CA3 border and propagated toward CA1. To determine how β-AR modulates spatiotemporal characteristics of the emergent IBs, we used the β-AR agonist isoproterenol (ISO). ISO significantly reduced the spatiotemporal extent and propagation velocity of the IBs and significantly altered network activity in the 1- to 20-Hz range. Dual whole cell recordings of the IBs in CA3/CA1 pyramidal cells and optical analysis of those regions showed that ISO application reduced interpyramidal and interregional synchrony during the IBs. In addition, ISO significantly reduced duration not only of the shorter duration IBs but also the prolonged ILEs in 4-AP. To test whether the decrease in ILE duration was model dependent, we used a different hyperexcitability model, zero magnesium (0 Mg2+). Prolonged ILEs were readily formed in 0 Mg2+, and addition of ISO significantly reduced their durations. Taken together, these novel results provide evidence that β-AR activation dynamically reshapes the spatiotemporal activity patterns in hyperexcitable circuits by altering network rhythmogenesis, propagation velocity, and intercellular/regional synchronization.

scholarly journals Interneuron-specific plasticity at parvalbumin and somatostatin inhibitory synapses onto CA1 pyramidal neurons shapes hippocampal output

2019 ◽  
Author(s):  
Matt Udakis ◽  
Victor Pedrosa ◽  
Sophie E.L. Chamberlain ◽  
Claudia Clopath ◽  
Jack R Mellor
Keyword(s):  
Pyramidal Neurons ◽  
Physiological Activity ◽  
Activity Patterns ◽  
Pyramidal Cells ◽  
Network Activity ◽  
Inhibitory Synapses ◽  
Ca1 Pyramidal Cells ◽  
Hippocampal Cell ◽  
Hippocampal Network

SummaryThe formation and maintenance of spatial representations within hippocampal cell assemblies is strongly dictated by patterns of inhibition from diverse interneuron populations. Although it is known that inhibitory synaptic strength is malleable, induction of long-term plasticity at distinct inhibitory synapses and its regulation of hippocampal network activity is not well understood. Here, we show that inhibitory synapses from parvalbumin and somatostatin expressing interneurons undergo long-term depression and potentiation respectively (PV-iLTD and SST-iLTP) during physiological activity patterns. Both forms of plasticity rely on T-type calcium channel activation to confer synapse specificity but otherwise employ distinct mechanisms. Since parvalbumin and somatostatin interneurons preferentially target perisomatic and distal dendritic regions respectively of CA1 pyramidal cells, PV-iLTD and SST-iLTP coordinate a reprioritisation of excitatory inputs from entorhinal cortex and CA3. Furthermore, circuit-level modelling reveals that PV-iLTD and SST-iLTP cooperate to stabilise place cells while facilitating representation of multiple unique environments within the hippocampal network.

scholarly journals Computer modeling of hippocampal CA1 pyramidal cells - a tool for in silico experiments

2015 ◽  
Vol 61 (1) ◽  
pp. 15-24 ◽  
Author(s):  
Júlia Metz ◽  
T. Szilágyi ◽  
M. Perian ◽  
K. Orbán-Kis
Keyword(s):  
Pyramidal Cell ◽  
In Silico ◽  
Action Potentials ◽  
Firing Pattern ◽  
Cell Model ◽  
Pyramidal Cells ◽  
Spike Timing ◽  
Network Activity ◽  
Ca1 Pyramidal Cells ◽  
Neuronal Network Activity

Abstract Objective. In silico experiments use mathematical models that capture as much as possible from the properties of the biological system under investigation. Our aim was to test the publicly available CA1 pyramidal cell models using the same simulation tasks, to compare them, and provide a systematic overview of their properties in order to improve the usefulness of these models as a tool for in silico experiments. Methods. Parameters describing the morphology of the cells and the implemented biophysical mechanisms were collected from the Model DB database of Sense Lab Project. This data was analyzed in correlation with the purpose for which each particular model was developed. Multicompartmental simulations were run using the Neuron modeling platform. The properties of the action potentials generated in response to current injection, the firing pattern and the dendritic back-propagation were analyzed. Results. The studied models were optimized to explore different physiological and pathological properties of the CA1 pyramidal cells. We could identify four broad classes of models focusing on: (i) initiation of the action potential, firing pattern and spike timing, (ii) dendritic backpropagation, (iii) dendritic integration of synaptic inputs and (iv) neuronal network activity. Despite the large variation of the active conductances implemented in the models, the properties of the individual action potentials were quite similar, but even the most complex models could not reproduce all studied biological phenomena. Conclusions. At the moment the “perfect” pyramidal cell model is not yet available. Our work, hopefully, will help finding the best model for each scientific question under investigation.

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

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.

Acute Clozapine Suppresses Synchronized Pyramidal Synaptic Network Activity by Increasing Inhibition in the Ferret Prefrontal Cortex

2007 ◽  
Vol 97 (2) ◽  
pp. 1196-1208 ◽  
Author(s):  
Wen-Jun Gao
Keyword(s):  
Prefrontal Cortex ◽  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Suppressive Effect ◽  
Network Activity ◽  
Cortical Circuitry ◽  
Prefrontal Cortical ◽  
Recurrent Excitation ◽  
Whole Cell Recordings

Recent studies have indicated that impaired neural circuitry in the prefrontal cortex is a prominent feature of the neuropathology of schizophrenia. Clozapine is one of the most effective antipsychotic drugs used for this debilitating disease. Despite its effectiveness, the mechanism by which clozapine acts on prefrontal cortical circuitry remains poorly understood. In this study, in vitro multiple whole cell recordings were performed in slices of the ferret prefrontal cortex. Clozapine, which effectively inhibited the spontaneous synchronized network activities in the prefrontal neurons, achieved the suppressive effect by decreasing the recurrent excitation among pyramidal neurons and by enhancing the inhibitory inputs onto pyramidal cells through a likely network mechanism. Indeed, under the condition of disinhibition, the depressing effects were reversed and clozapine enhanced the recurrent excitation. These results suggest that the therapeutic actions of clozapine in alleviating the positive symptoms of schizophrenia are achieved, at least partially, through the readjustment of synaptic balance between the excitation and inhibition in the prefrontal cortical circuitry.

scholarly journals Synaptic GABAA Activation Inhibits AMPA-Kainate Receptor–Mediated Bursting in the Newborn (P0–P2) Rat Hippocampus

2000 ◽  
Vol 83 (1) ◽  
pp. 359-366 ◽  
Author(s):  
Karri Lamsa ◽  
J. Matias Palva ◽  
Eva Ruusuvuori ◽  
Kai Kaila ◽  
Tomi Taira
Keyword(s):  
Pyramidal Neurons ◽  
Field Potential ◽  
Pyramidal Cells ◽  
Neuronal Population ◽  
Excitatory Input ◽  
Calcium Oscillations ◽  
Rat Hippocampus ◽  
Network Activity ◽  
Ca1 Pyramidal Cells

The mechanisms of synaptic transmission in the rat hippocampus at birth are assumed to be fundamentally different from those found in the adult. It has been reported that in the CA3-CA1 pyramidal cells a conversion of “silent” glutamatergic synapses to conductive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) synapses starts gradually after P2. Further, GABA via its depolarizing action seems to give rise to grossly synchronous yet slow calcium oscillations. Therefore, GABA is generally thought to have a purely excitatory rather than an inhibitory role during the first postnatal week. In the present study field potential recordings and gramicidin perforated and whole cell clamp techniques as well as K+-selective microelectrodes were used to examine the relative contributions of AMPA and GABAA receptors to network activity of CA3-CA1 pyramidal cells in the newborn rat hippocampus. As early as postnatal day( P 0–P2), highly coherent spontaneous firing of CA3 pyramidal cells was seen in vitro. Negative-going extracellular spikes confined to periodic bursts (interval 16 ± 3 s) consisting of 2.9 ± 0.1 spikes were observed in stratum pyramidale. The spikes were accompanied by AMPA-R–mediated postsynaptic currents (PSCs) in simultaneously recorded pyramidal neurons (7.6 ± 3.0 unitary currents per burst). In CA1 pyramidal cells synchronous discharging of CA3 circuitry produced a barrage of AMPA currents at >20 Hz frequencies, thus demonstrating a transfer of the fast CA3 network activity to CA1 area. Despite its depolarizing action, GABAA-R–mediated transmission appeared to exert inhibition in the CA3 pyramidal cell population. The GABAA-R antagonist bicuculline hypersynchronized the output of glutamatergic CA3 circuitry and increased the network-driven excitatory input to the pyramidal neurons, whereas the GABAA-R agonist muscimol (100 nM) did the opposite. However, the occurrence of unitary GABAA-R currents was increased after muscimol application from 0.66 ± 0.16 s−1 to 1.43 ± 0.29 s−1. It was concluded that AMPA synapses are critical in the generation of spontaneous high-frequency bursts in CA3 as well as in CA3-CA1 transmission as early as P0–P2 in rat hippocampus. Concurrently, although GABAA-R–mediated depolarization may excite hippocampal interneurons, in CA3 pyramidal neurons it can restrain excitatory inputs and limit the size of the activated neuronal population.

scholarly journals Learning-induced sequence reactivation during sharp-wave ripples: a computational study

2017 ◽  
Author(s):  
Paola Malerba ◽  
Katya Tsimring ◽  
Maxim Bazhenov
Keyword(s):  
Computational Study ◽  
Activity Patterns ◽  
Pyramidal Cells ◽  
Learning Task ◽  
Network Activity ◽  
Sharp Wave ◽  
High Frequency Oscillations ◽  
Excitatory Activity ◽  
Hippocampal Network ◽  
Synaptic Changes

AbstractDuring sleep, memories formed during the day are consolidated in a dialogue between cortex and hippocampus. The reactivation of specific neural activity patterns – replay – during sleep has been observed in both structures and is hypothesized to represent a neuronal substrate of consolidation. In the hippocampus, replay happens during sharp wave – ripples (SWR), short bouts of excitatory activity in area CA3 which induce high frequency oscillations in area CA1. In particular, recordings of hippocampal cells which spike at a specific location (‘place cells’) show that recently learned trajectories are reactivated during SWR in the following sleep SWR. Despite the importance of sleep replay, its underlying neural mechanisms are still poorly understood.We developed a model of SWR activity, to study the effects of learning-induced synaptic changes on spontaneous sequence reactivation during SWR. The model implemented a paradigm including three epochs: Pre-sleep, learning and Post-sleep activity. We first tested the effects of learning on the hippocampal network activity through changes in a minimal number of synapses connecting selected pyramidal cells. We then introduced an explicit trajectory-learning task to the model, to obtain behavior-induced synaptic changes. The model revealed that the recently learned trajectory reactivates during sleep more often than other trajectories in the training field. The study predicts that the gain of reactivation rate during sleep following vs sleep preceding learning for a trained sequence of pyramidal cells depends on Pre-sleep activation of the same sequence, and on the amount of trajectory repetitions included in the training phase.

scholarly journals Seizures as imbalanced up states: excitatory and inhibitory conductances during seizure-like events

2013 ◽  
Vol 109 (5) ◽  
pp. 1296-1306 ◽  
Author(s):  
Jokūbas Žiburkus ◽  
John R. Cressman ◽  
Steven J. Schiff
Keyword(s):  
Neural Network ◽  
Pyramidal Cells ◽  
Cell Types ◽  
The Body ◽  
Network Activity ◽  
Ca1 Pyramidal Cells ◽  
Up States ◽  
Termination Phase ◽  
Initiation Stage

Precisely timed and dynamically balanced excitatory (E) and inhibitory (I) conductances underlie the basis of neural network activity. Normal E/I balance is often shifted in epilepsy, resulting in neuronal network hyperexcitability and recurrent seizures. However, dynamics of the actual excitatory and inhibitory synaptic conductances ( ge and gi, respectively) during seizures remain unknown. To study the dynamics of E and I network balance, we calculated ge and gi during the initiation, body, and termination of seizure-like events (SLEs) in the rat hippocampus in vitro. Repetitive emergent SLEs in 4-aminopyridine (100 μM) and reduced extracellular magnesium (0.6 mM) were recorded in the identified CA1 pyramidal cells (PC) and oriens-lacunosum moleculare (O-LM) interneurons. Calculated ge/ gi ratio dynamics showed that the initiation stage of the SLEs was dominated by inhibition in the PCs and was more balanced in the O-LM cells. During the body of the SLEs, the balance shifted toward excitation, with ge and gi peaking in both cell types at nearly the same time. In the termination phase, PCs were again dominated by inhibition, whereas O-LM cells experienced persistent excitatory synaptic barrage. In this way, increased excitability of interneurons may play roles in both seizure initiation (Žiburkus J, Cressman JR, Barreto E, Schiff SJ. J Neurophysiol 95: 3948–3954, 2006) and in their termination. Overall, SLE stages can be characterized in PC and O-LM cells by dynamically distinct changes in the balance of ge and gi, where a temporal sequence of imbalance shifts with the changing firing patterns of the cellular subtypes comprising the hyperexcitable microcircuits.

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