Microtechnologies for Neurobiology

2010 ◽  
Author(s):  
Henry C. Zeringue
Keyword(s):  
Genetic Programming ◽  
Spatial Information ◽  
Structural Connectivity ◽  
Propagation Delay ◽  
Network Activity ◽  
Local Network ◽  
Oscillatory Activity ◽  
Memory And Attention ◽  
High Level

Oscillatory activity in cortical networks is thought to provide the foundation for many high-level processes including working memory and attention. It has been shown that spatial information propagation delay and connectivity density can determine the innate properties of local network activity. The initial formation of neuronal networks in the central nervous system occurs due to the interaction of the genetic programming of the cells and the presentation of external molecular cues. The activity-driven refinement that occurs later, giving rise to the highly complex networks within the brain, are dependent on the initial anatomical formation and structural connectivity which occurs without external activity cues. We describe technologies used to (1) modulate the genetic programming of neurons and (2) precisely control temporal and spatial presentation of environmental cues in vitro. We are exploring the ability to define simple oscillatory networks using these experimental techniques.

scholarly journals Contribution of near-threshold currents to intrinsic oscillatory activity in rat medial entorhinal cortex layer II stellate cells

2013 ◽  
Vol 109 (2) ◽  
pp. 445-463 ◽  
Author(s):  
Anne Boehlen ◽  
Christian Henneberger ◽  
Uwe Heinemann ◽  
Irina Erchova
Keyword(s):  
Entorhinal Cortex ◽  
Neuronal Excitability ◽  
Spatial Information ◽  
Sodium Current ◽  
Stellate Cells ◽  
Frequency Component ◽  
Oscillatory Activity ◽  
Potential Oscillations ◽  
Near Threshold

The temporal lobe is well known for its oscillatory activity associated with exploration, navigation, and learning. Intrinsic membrane potential oscillations (MPOs) and resonance of stellate cells (SCs) in layer II of the entorhinal cortex are thought to contribute to network oscillations and thereby to the encoding of spatial information. Generation of both MPOs and resonance relies on the expression of specific voltage-dependent ion currents such as the hyperpolarization-activated cation current ( IH), the persistent sodium current ( INaP), and the noninactivating muscarine-modulated potassium current ( IM). However, the differential contributions of these currents remain a matter of debate. We therefore examined how they modify neuronal excitability near threshold and generation of near-threshold MPOs and resonance in vitro. We found that resonance mainly relied on IH and was reduced by IH blockers and modulated by cAMP and an IM enhancer but that neither of the currents exhibited full control over MPOs in these cells. As previously reported, IH controlled a theta-frequency component of MPOs such that blockade of IH resulted in fewer regular oscillations that retained low-frequency components and high peak amplitude. However, pharmacological inhibition and augmentation of IM also affected MPO frequencies and amplitudes. In contrast to other cell types, inhibition of INaP did not result in suppression of MPOs but only in a moderation of their properties. We reproduced the experimentally observed effects in a single-compartment stochastic model of SCs, providing further insight into the interactions between different ionic conductances.

scholarly journals Modulation of Network Oscillatory Activity and GABAergic Synaptic Transmission by CB1 Cannabinoid Receptors in the Rat Medial Entorhinal Cortex

2008 ◽  
Vol 2008 ◽  
pp. 1-12 ◽  
Author(s):  
Nicola H. Morgan ◽  
Ian M. Stanford ◽  
Gavin L. Woodhall
Keyword(s):  
Synaptic Transmission ◽  
Cannabinoid Receptors ◽  
Brain Regions ◽  
Synaptic Activity ◽  
Network Activity ◽  
Oscillatory Activity ◽  
Gabaergic Neurotransmission ◽  
Network Oscillations ◽  
Gabaergic Synaptic Transmission

Cannabinoids modulate inhibitory GABAergic neurotransmission in many brain regions. Within the temporal lobe, cannabinoid receptors are highly expressed, and are located presynaptically at inhibitory terminals. Here, we have explored the role of type-1 cannabinoid receptors (CB1Rs) at the level of inhibitory synaptic currents and field-recorded network oscillations. We report that arachidonylcyclopropylamide (ACPA; 10 M), an agonist at CB1R, inhibits GABAergic synaptic transmission onto both superficial and deep medial entorhinal (mEC) neurones, but this has little effect on network oscillations in beta/gamma frequency bands. By contrast, the CB1R antagonist/inverse agonist LY320135 (500 nM), increased GABAergic synaptic activity and beta/gamma oscillatory activity in superficial mEC, was suppressed, whilst that in deep mEC was enhanced. These data indicate that cannabinoid-mediated effects on inhibitory synaptic activity may be constitutively active in vitro, and that modulation of CB1R activation using inverse agonists unmasks complex effects of CBR function on network activity.

scholarly journals The transformation of synaptic to system plasticity in motor output from the sacral cord of the adult mouse

2015 ◽  
Vol 114 (3) ◽  
pp. 1987-2004 ◽  
Author(s):  
Mingchen C. Jiang ◽  
Sherif M. Elbasiouny ◽  
William F. Collins ◽  
C. J. Heckman
Keyword(s):  
Synaptic Plasticity ◽  
Adult Mouse ◽  
Motor Output ◽  
Network Activity ◽  
System Level ◽  
Local Network ◽  
System Transformation ◽  
Short Term ◽  
Local Networks

Synaptic plasticity is fundamental in shaping the output of neural networks. The transformation of synaptic plasticity at the cellular level into plasticity at the system level involves multiple factors, including behavior of local networks of interneurons. Here we investigate the synaptic to system transformation for plasticity in motor output in an in vitro preparation of the adult mouse spinal cord. System plasticity was assessed from compound action potentials (APs) in spinal ventral roots, which were generated simultaneously by the axons of many motoneurons (MNs). Synaptic plasticity was assessed from intracellular recordings of MNs. A computer model of the MN pool was used to identify the middle steps in the transformation from synaptic to system behavior. Two input systems that converge on the same MN pool were studied: one sensory and one descending. The two synaptic input systems generated very different motor outputs, with sensory stimulation consistently evoking short-term depression (STD) whereas descending stimulation had bimodal plasticity: STD at low frequencies but short-term facilitation (STF) at high frequencies. Intracellular and pharmacological studies revealed contributions from monosynaptic excitation and stimulus time-locked inhibition but also considerable asynchronous excitation sustained from local network activity. The computer simulations showed that STD in the monosynaptic excitatory input was the primary driver of the system STD in the sensory input whereas network excitation underlies the bimodal plasticity in the descending system. These results provide insight on the roles of plasticity in the monosynaptic and polysynaptic inputs converging on the same MN pool to overall motor plasticity.

scholarly journals GABA–glutamate supramammillary neurons control theta and gamma oscillations in the dentate gyrus during paradoxical (REM) sleep

2020 ◽  
Vol 225 (9) ◽  
pp. 2643-2668 ◽  
Author(s):  
Francesca Billwiller ◽  
Laura Castillo ◽  
Heba Elseedy ◽  
Anton Ivanovich Ivanov ◽  
Jennyfer Scapula ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Rem Sleep ◽  
Slow Wave Sleep ◽  
Granule Cells ◽  
Structural Connectivity ◽  
Gamma Oscillations ◽  
Network Activity ◽  
Projection Neurons ◽  
Gamma Power

AbstractSeveral studies suggest that neurons from the lateral region of the SuM (SuML) innervating the dorsal dentate gyrus (DG) display a dual GABAergic and glutamatergic transmission and are specifically activated during paradoxical (REM) sleep (PS). The objective of the present study is to characterize the anatomical, neurochemical and electrophysiological properties of the SuML-DG projection neurons and to determine how they control DG oscillations and neuronal activation during PS and other vigilance states. For this purpose, we combine structural connectivity techniques using neurotropic viral vectors (rabies virus, AAV), neurochemical anatomy (immunohistochemistry, in situ hybridization) and imaging (light, electron and confocal microscopy) with in vitro (patch clamp) and in vivo (LFP, EEG) optogenetic and electrophysiological recordings performed in transgenic VGLUT2-cre male mice. At the cellular level, we show that the SuML-DG neurons co-release GABA and glutamate on dentate granule cells and increase the activity of a subset of DG granule cells. At the network level, we show that activation of the SuML-DG pathway increases theta power and frequency during PS as well as gamma power during PS and waking in the DG. At the behavioral level, we show that the activation of this pathway does not change animal behavior during PS, induces awakening during slow wave sleep and increases motor activity during waking. These results suggest that the SuML-DG pathway is capable of supporting the increase of theta and gamma power in the DG observed during PS and plays an important modulatory role of DG network activity during this state.

scholarly journals Channelrhodopsin variants engage distinct patterns of network activity

2018 ◽  
Author(s):  
Na Young Jun ◽  
Jessica A. Cardin
Keyword(s):  
Network Activity ◽  
Local Network ◽  
Gamma Range ◽  
Cell Type Specific ◽  
Evoked Activity ◽  
Gamma Band Activity ◽  
Circuit Function ◽  
Temporal Profiles

AbstractChannelrhodopsins (ChRs) are light-gated ion channels that enable cell type-specific activation of neurons or neural circuits. Channelrhodopsin-2 has been widely used as a tool to probe circuit function in vitro and in vivo. Several recently developed ChR variants are characterized by faster kinetics and reduced desensitization. However, little is known about how their varying properties may regulate their interaction with local network dynamics. We compared ChR-evoked patterns of multi-unit activity and local field potentials in primary visual cortex of mice expressing three ChR variants with distinct temporal profiles: Chronos, Chrimson, and ChR2. We assessed overall activation of by measuring the amplitude and temporal progression of evoked spiking. Using gamma-range (30-80Hz) LFP power as an assay for local network engagement, we examined the recruitment of cortical network activity by each tool. All ChR variants caused light-evoked increases in firing in vivo, but each demonstrated different temporal patterning of evoked activity. In addition, the three ChRs had distinct effects on cortical gamma-band activity. Our findings suggest that variations in the kinetics of optogenetic tools can substantially affect their efficacy in neural networks in vivo, as well as the manner in which their activation engages circuit resonance.

Spontaneous Development of Synchronous Oscillatory Activity During Maturation of Cortical Networks In Vitro

2002 ◽  
Vol 88 (5) ◽  
pp. 2196-2206 ◽  
Author(s):  
Thoralf Opitz ◽  
Ana D. De Lima ◽  
Thomas Voigt
Keyword(s):  
Large Scale ◽  
Reversal Potential ◽  
Neuronal Population ◽  
Network Activity ◽  
Oscillatory Activity ◽  
Pharmacological Intervention ◽  
Resting Membrane Potential ◽  
Cortical Networks ◽  
Synchronous Network

Recent studies have focused attention on mechanisms of spontaneous large-scale wavelike activity during early development of the neocortex. In this study, we describe and characterize synchronous neuronal activity that occurs in cultured cortical networks naturally without pharmacological intervention. The synchronous activity that can be detected by means of Fluo-3 fluorescence imaging starts to develop at the beginning of the second week in culture and eventually includes the entire neuronal population about 1 wk later. A synchronous increase of [Ca2+]i in the neuronal population is associated with a burst of action potentials riding on a long-lasting depolarization recorded in a single cell. It is suggested that this depolarization results directly from synaptic current, which was comprised of at least three different components mediated by AMPA, N-methyl-d-aspartate (NMDA), and GABAA receptors. We never observed a gradually depolarizing pacemaker potential and found no evidence for a change of excitability during inter-burst periods. However, we found evidence for a period of synaptic depression after bursts. Network excitability recovers gradually over seconds from this depression that can explain the episodic nature of spontaneous network activity. Using pharmacological manipulation to investigate the propagation of activity in the network, we show that synchronous network activity depends on both glutamatergic and GABAAergic neurotransmission during a brief period. Reversal potential of GABAA receptor-mediated current was found to be significantly more positive than resting membrane potential both at 1 and 2 wk in culture, suggesting depolarizing action of GABA. However, in cultures older than 2 wk, inhibition of GABAAreceptors does not result in block of synchronous network activity but in modulation of burst width and frequency.

Fast Network Oscillations in the Rat Dentate Gyrus In Vitro

2002 ◽  
Vol 87 (2) ◽  
pp. 1165-1168 ◽  
Author(s):  
Stephen K. Towers ◽  
Fiona E. N. LeBeau ◽  
Tengis Gloveli ◽  
Roger D. Traub ◽  
Miles A. Whittington ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Hippocampal Formation ◽  
Molecular Layer ◽  
Hippocampal Slices ◽  
Network Activity ◽  
Oscillatory Activity ◽  
Gamma Frequency ◽  
Fast Network

The dentate gyrus is a prominent source of gamma frequency activity in the hippocampal formation in vivo. Here we show that transient epochs of gamma frequency network activity (67 ± 12 Hz) can be generated in the dentate gyrus of rat hippocampal slices, following brief pressure ejections of a high-molarity potassium solution onto the molecular layer. Oscillatory activity remains synchronized over distances >300 μm and is accompanied by a modest rise in [K+]o. Gamma frequency oscillations were abolished by a GABAA receptor antagonist demonstrating their dependence on rhythmic inhibition. However, in many cases, higher frequency oscillations (>80 Hz) remained in the absence of synaptic transmission, thus demonstrating that nonsynaptic factors may underlie fast oscillatory activity.

scholarly journals Nested oscillatory dynamics in cortical organoids model early human brain network development

2018 ◽  
Author(s):  
Cleber A. Trujillo ◽  
Richard Gao ◽  
Priscilla D. Negraes ◽  
Isaac A. Chaim ◽  
Alain Domissy ◽  
...  
Keyword(s):  
Human Brain ◽  
Network Activity ◽  
Brain Maturation ◽  
Oscillatory Activity ◽  
List Type ◽  
Complex Activity ◽  
Neuronal Computation ◽  
Oscillatory Network

SUMMARYStructural and transcriptional changes during early brain maturation follow fixed developmental programs defined by genetics. However, whether this is true for functional network activity remains unknown, primarily due to experimental inaccessibility of the initial stages of the living human brain. Here, we developed cortical organoids that spontaneously display periodic and regular oscillatory network events that are dependent on glutamatergic and GABAergic signaling. These nested oscillations exhibit cross-frequency coupling, proposed to coordinate neuronal computation and communication. As evidence of potential network maturation, oscillatory activity subsequently transitioned to more spatiotemporally irregular patterns, capturing features observed in preterm human electroencephalography (EEG). These results show that the development of structured network activity in the human neocortex may follow stable genetic programming, even in the absence of external or subcortical inputs. Our approach provides novel opportunities for investigating and manipulating the role of network activity in the developing human cortex.HIGHLIGHTSEarly development of human functional neural networks and oscillatory activity can be modeled in vitro.Cortical organoids exhibit phase-amplitude coupling between delta oscillation (2 Hz) and high-frequency activity (100-400 Hz) during network-synchronous events.Differential role of glutamate and GABA in initiating and maintaining oscillatory network activity.Developmental impairment of MECP2-KO cortical organoids impacts the emergence of oscillatory activity.Cortical organoid network electrophysiological signatures correlate with human preterm neonatal EEG features.eTOCBrain oscillations are a candidate mechanism for how neural populations are temporally organized to instantiate cognition and behavior. Cortical organoids initially exhibit periodic and highly regular nested oscillatory network events that eventually transition to more spatiotemporally complex activity, capturing features of late-stage preterm infant electroencephalography. Functional neural circuitry in cortical organoids exhibits emergence and development of oscillatory network dynamics similar to those found in the developing human brain.

scholarly journals Amyloid Beta Peptides Differentially Affect Hippocampal Theta Rhythms In Vitro

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Armando I. Gutiérrez-Lerma ◽  
Benito Ordaz ◽  
Fernando Peña-Ortega
Keyword(s):  
Amyloid Beta ◽  
Neuronal Network ◽  
Hippocampal Slices ◽  
Network Activity ◽  
Oscillatory Activity ◽  
High Concentration ◽  
Cellular Mechanisms ◽  
Experimental Conditions ◽  
Hippocampal Theta

Soluble amyloid beta peptide (Aβ) is responsible for the early cognitive dysfunction observed in Alzheimer's disease. Both cholinergically and glutamatergically induced hippocampal theta rhythms are related to learning and memory, spatial navigation, and spatial memory. However, these two types of theta rhythms are not identical; they are associated with different behaviors and can be differentially modulated by diverse experimental conditions. Therefore, in this study, we aimed to investigate whether or not application of soluble Aβ alters the two types of theta frequency oscillatory network activity generated in rat hippocampal slices by application of the cholinergic and glutamatergic agonists carbachol or DHPG, respectively. Due to previous evidence that oscillatory activity can be differentially affected by different Aβ peptides, we also compared Aβ25−35 and Aβ1−42 for their effects on theta rhythms in vitro at similar concentrations (0.5 to 1.0 μM). We found that Aβ25−35 reduces, with less potency than Aβ1−42, carbachol-induced population theta oscillatory activity. In contrast, DHPG-induced oscillatory activity was not affected by a high concentration of Aβ25−35 but was reduced by Aβ1−42. Our results support the idea that different amyloid peptides might alter specific cellular mechanisms related to the generation of specific neuronal network activities, instead of exerting a generalized inhibitory effect on neuronal network function.

NMDA Receptor-Mediated Oscillatory Activity in the Neonatal Rat Spinal Cord Is Serotonin Dependent

1998 ◽  
Vol 79 (5) ◽  
pp. 2804-2808 ◽  
Author(s):  
Jason N. Maclean ◽  
Kristine C. Cowley ◽  
Brian J. Schmidt
Keyword(s):  
Spinal Cord ◽  
Nmda Receptor ◽  
Motor Behavior ◽  
Neonatal Rat ◽  
Network Activity ◽  
Oscillatory Activity ◽  
Rat Spinal Cord ◽  
Cell Level ◽  
Receptor Antagonists

MacLean, Jason N., Kristine C. Cowley, and Brian J. Schmidt. NMDA receptor-mediated oscillatory activity in the neonatal rat spinal cord is serotonin dependent. J. Neurophysiol. 79: 2804–2808, 1998. The effect of serotonin (5-HT) receptor blockade on rhythmic network activity and on N-methyl-d-aspartate (NMDA) receptor-induced membrane voltage oscillations was examined using an in vitro neonatal rat spinal cord preparation. Pharmacologically induced rhythmic hindlimb activity, monitored via flexor and extensor electroneurograms or ventral root recordings, was abolished by 5-HT receptor antagonists. Intrinsic motoneuronal voltage oscillations, induced by NMDA in the presence of tetrodotoxin (TTX), either were abolished completely or transformed to long-lasting voltage shifts by 5-HT receptor antagonists. Conversely, 5-HT application facilitated the expression of NMDA-receptor–mediated rhythmic voltage oscillations. The results suggest that an interplay between 5-HT and NMDA receptor actions may be critical for the production of rhythmic motor behavior in the mammalian spinal cord, both at the network and single cell level.

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