191 research outputs found
Intracellular, in vitro somatic membrane potential recordings from whole cell patch clamped rodent hippocampal CA1 neurons
No full textThis data set contains the raw data files of current injection sweeps from somatic injections of the experimental cells (mouse and rat under standard “control” in vitro recording conditions) that were used to constrain the model cells of the model CA1 neural network published in: Marianne J. Bezaire, Ivan Raikov, Kelly Burk, Dhrumil Vyas, and Ivan Soltesz. Interneuronal mechanisms of hippocampal theta oscillations in full-scale models of the CA1 circuit. Under Review, 2016. Results from the experiments are described in:
Sang-Hun Lee, Ivan Marchionni, Marianne Bezaire, Csaba Varga, Nathan Danielson, Matthew Lovett-Barron, Attila Losonczy, and Ivan Soltesz. Parvalbumin-positive basket cells differentiate among hippocampal pyramidal cells. Neuron, 82(5):1129–1144, 2014. doi: 10.1016/j.neuron.2014.03.034.
Esther Krook-Magnuson, Lillian Luu, Sang-Hun Lee, Csaba Varga, and Ivan Soltesz. Ivy and neurogliaform interneurons are a major target of µ-opioid receptor modulation. The Journal of Neuroscience, 31(42):14861–14870, 2011. doi: 10.1523/JNEUROSCI.2269-11.2011.
Sang-Hun Lee, Csaba Foldy, and Ivan Soltesz. Distinct endocannabinoid control of GABA release at perisomatic and dendritic synapses in the hippocampus. J. Neurosci., 30:7993–8000, 2010. doi: 10.1523/JNEUROSCI.6238-09.2010
Simulation results from a network model of the isolated hippocampal CA1 subfield in rat
No full textThe data set contains simulation results from the publication:
Marianne J. Bezaire, Ivan Raikov, Kelly Burk, NEURON Developers, Dhrumil Vyas, and Ivan Soltesz. From full scale to rationally reduced small network models: application to theta-related firing of the isolated CA1 subfield. eLife (2016)
Ripple‐related firing of identified deep CA 1 pyramidal cells in chronic temporal lobe epilepsy in mice
No full textFunctional fission of parvalbumin interneuron classes during fast network events.
No full textFast spiking, parvalbumin (PV) expressing hippocampal interneurons are classified into basket, axo-axonic (chandelier), and bistratified cells. These cell classes play key roles in regulating local circuit operations and rhythmogenesis by releasing GABA in precise temporal patterns onto distinct domains of principal cells. In this study, we show that each of the three major PV cell classes further splits into functionally distinct sub-classes during fast network events in vivo. During the slower (<10 Hz) theta oscillations, each cell class exhibited its own characteristic, relatively uniform firing behavior. However, during faster (>90 Hz) oscillations, within-class differences in PV interneuron discharges emerged, which segregated along specific features of dendritic structure or somatic location. Functional divergence of PV sub-classes during fast but not slow network oscillations effectively doubles the repertoire of spatio-temporal patterns of GABA release available for rapid circuit operations
Parvalbumin-positive basket cells differentiate among hippocampal pyramidal cells.
No full textSummaryCA1 pyramidal cells (PCs) are not homogeneous but rather can be grouped by molecular, morphological, and functional properties. However, less is known about synaptic sources differentiating PCs. Using paired recordings in vitro, two-photon Ca2+ imaging in vivo, and computational modeling, we found that parvalbumin-expressing basket cells (PVBCs) evoked greater inhibition in CA1 PCs located in the deep compared to superficial layer of stratum pyramidale. In turn, analysis of reciprocal connectivity revealed more frequent excitatory inputs to PVBCs by superficial PCs, demonstrating bias in target selection by both the excitatory and inhibitory local connections in CA1. Additionally, PVBCs further segregated among deep PCs, preferentially innervating the amygdala-projecting PCs but receiving preferential excitation from the prefrontal cortex-projecting PCs, thus revealing distinct perisomatic inhibitory interactions between separate output channels. These results demonstrate the presence of heterogeneous PVBC-PC microcircuits, potentially contributing to the sparse and distributed structure of hippocampal network activity.Video Abstrac
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Modeling physiological oscillations in a biologically constrained CA1 network from two perspectives: full-scale parallel network and rationally reduced Network Clamp
No full textI developed a full-scale, biologically constrained model of hippocampal CA1 subfield that is capable of spontaneous theta and gamma oscillations with distinct interneuronal phase preferences. In addition to structural constraints on the cell numbers and connectivity, experimental observations drove the development of the electrophysiology for the nine cell types and their synapses. To characterize and experimentally constrain the model, I designed and developed a custom software tool called SimTracker. SimTracker works with my NEURON code template to enable efficient coding, simulation design and execution, and analysis of results for parallel network NEURON simulations. I also created the Network Clamp, a software tool that implements the concept of a rational method for reducing a full-scale parallel network model to a small, yet biologically constrained model whose simulations can be run on a personal computer. Here I characterize the physiological oscillations displayed by the model. Additionally, I explore the parameter-space of the model by studying its oscillatory properties while manipulating its connectivity, excitation level, and synapse kinetics. This dual approach model is well characterized, flexible and accessible, and it represents a useful collation of experimental knowledge as well as a significant technical advance in neural network modeling
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Control of spatial memory and seizures by hippocampal mossy cells
No full textTemporal lobe epilepsy is the most common neurological disorder in adults and one of the most medically refractory. In order to develop new, more effective therapeutical approaches for TLE, we need a more complete understanding of the hippocampal structural and functional alterations underlying seizure activity and comorbid cognitive deficits. We investigated the contribution of two excitatory cell populations in the hippocampal dentate gyrus to ictal activity and spatial memory, the enigmatic hilar mossy cells and the granule cells, utilizing a combination of optogenetic, electrophysiological, and behavioral approaches in awake, behaving animals. Our main findings are: 1) decreased mossy cell activity during spontaneous, electrographic seizures permits further generalization of electrographic seizures into behavioral seizures; 2) mossy cells play a protective and anti-epileptic role in preventing seizure propagation; 3) mossy cells are necessary for encoding of spatial information, and a loss or decrease in mossy cell activity leads to memory impairments; 4) restoration of the dentate gyrus to a hyperpolarized state can robustly control seizure activity in chronic temporal lobe epilepsy, while stimulation of dentate gyrus granule cells leads to convulsive seizures. Our work has important implications for future therapeutical approaches. Our findings suggest that strategies to target the dentate gyrus microcircuitry, for example, by limiting MC loss, directly exciting surviving MCs, or inhibiting granule cells, may provide powerful treatment options for seizure control
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Computational Models of the Hippocampus in Radiation and Epilepsy
No full textComputational modeling of neuronal networks enables the study of variables in isolation while approximating the biological state. In conditions such as the exposure to radiation and epilepsy, a large number of structural and network parameters are altered, making the role of any individual abnormality unclear. The goal of the presented work is to develop realistic computational models of the hippocampus for the incorporation of experimental observations and to shed light on the relative importance and deleteriousness of pathological alterations. The Introduction summarizes our motivations and the utility of realistic computational models, particularly for the hippocampus, and gives a background for the abnormalities present in the irradiated and epileptic conditions. Chapter 1 describes our work translating our previous model to be compatible with parallel computing and then expanding the model to run at full-scale, with over a million neurons. It then outlines a methodology for the generation of computational models for the dendritic trees of granule cells, the most prevalent cell type in the dentate gyrus, using previous tools that contained a microscopic focus. In Chapter 2, we report an entirely new methodology for morphology generation that instead shifts the focus to the macroscopic neuroanatomy, growing dendrites within a realistic three-dimensional structure and enabling the population-level study of morphology. Chapter 3 describes a study in which our computational modeling was used to interpret experimental observations in area CA1 of the hippocampus after exposure to proton radiation. The study reports long-term but subtle changes in the passive properties of pyramidal neurons, the principal excitatory cell type in CA1, which were found in a computational model to have a surprisingly dramatic effect on network function. Chapter 4 reviews the ever-growing observations of the non-recurrent microscopic nature of seemingly repetitive macroscopic events in epilepsy. Chapter 5 provides the immediate next steps and future directions for computational modeling in health and disease, building on the foundation and framework provided in the previous chapters to suggest several avenues to bring computational models ever closer to the experimental, biological, and clinical conditions
Temporal Patterns and Depolarizing Actions of Spontaneous GABA<sub>A</sub> Receptor Activation in Granule Cells of the Early Postnatal Dentate Gyrus
No full text Hollrigel, Greg S., Stephen T. Ross, and Ivan Soltesz. Temporal patterns and depolarizing actions of spontaneous GABAA receptor activation in granule cells of the early postnatal dentate gyrus. J. Neurophysiol. 80: 2340–2351, 1998. Whole cell patch-clamp recordings were used to investigate the properties of the γ-aminobutyric acid type A (GABAA) receptor-mediated spontaneous synaptic events in immature granule cells of the developing, early postnatal day (P0–P6) rat dentate gyrus. With Cs-gluconate-filled whole cell patch pipettes at 0 mV in control medium, spontaneous inhibitory postsynaptic currents (sIPSCs) occurred in prominent bursts (peak amplitude of the bursts 406.9 ± 58.4 pA; intraburst IPSC frequency 71.0 ± 12.4 Hz) at 0.05 ± 0.02 Hz in every immature granule cell younger than P7. Between the bursts of IPSCs, lower frequency (1.7 ± 0.7 Hz), interburst IPSCs could be observed. Bicuculline and picrotoxin as well as the intracellularly applied chloride-channel blockers CsF− and 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid (DIDS) abolished the intraburst as well as the interburst IPSCs, indicating that the IPSCs were mediated by GABAA receptor channels. The bursts of IPSCs, but not the interburst IPSCs, were blocked by the simultaneous application of the glutamate receptor antagonists 2-amino-5-phosphovaleric acid and 6-cyano-7-nitroquinoxaline-2,3-dione, indicating the importance of the glutamatergic excitatory drive onto the interneurons in the early postnatal dentate gyrus. The spontaneously occurring excitatory postsynaptic currents in immature granule cells, observable after the intracellular blockade of GABAA receptor channels with CsF− and DIDS, appeared exclusively as single events at low frequencies, i.e., they did not occur in prominent bursts. Gramicidin-based perforated patch-clamp recordings determined that the reversal potential for the burst of IPSCs (−46.6 ± 3.1 mV) was more depolarized than the resting membrane potential (−54.2 ± 4.2 mV) but more hyperpolarized than the action potential threshold (−41.8 ± 1.7 mV). The depolarizing action of the bursts of synaptic events most often evoked only a single action potential per burst. Simultaneous whole cell patch recordings, with KCl-filled patch pipettes at −60 mV in current clamp from pairs of immature granule cells of the developing dentate gyrus, determined that the bursts of IPSPs took place in a similar temporal pattern but with imperfect synchrony in neighboring granule cells (average lag between the onsets of the bursts between granule cell pairs 77.7 ± 8.6 ms). These results show that the spontaneous activation of GABAA receptors in immature dentate granule cells displays unique properties that are distinct from the temporal patterns and biophysical features of spontaneous GABAA receptor activation taking place in the developing Ammon's horn and in the adult dentate gyrus. </jats:p
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