scholarly journals Impaired long-range synchronization of gamma oscillations in the neocortex of a mouse lacking Kv3.2 potassium channels

2012 ◽  
Vol 108 (3) ◽  
pp. 827-833 ◽  
Author(s):  
Michael Harvey ◽  
David Lau ◽  
Eugene Civillico ◽  
Bernardo Rudy ◽  
Diego Contreras
Keyword(s):  
Long Range ◽  
High Frequency ◽  
Single Cells ◽  
Critical Role ◽  
Pyramidal Cells ◽  
Gamma Oscillations ◽  
Network Activity ◽  
Inhibitory Interneurons ◽  
Phase Lag ◽  
Firing Properties

Inhibitory interneurons play a critical role in the generation of gamma (20–50 Hz) oscillations, either by forming mutually inhibitory networks or as part of recurrent networks with pyramidal cells. A key property of fast spiking interneurons is their ability to generate brief spikes and high-frequency spike trains with little accommodation. However, the role of their firing properties in network oscillations has not been tested in vivo. Studies in hippocampus in vitro have shown that high-frequency spike doublets in interneurons play a key role in the long-range synchronization of gamma oscillations with little phase lag despite long axonal conduction delays. We generated a knockout (KO) mouse lacking Kv3.2 potassium channel subunits, where infragranular inhibitory interneurons lose the ability both to sustain high-frequency firing and reliably generate high-frequency spike doublets. We recorded cortical local field potentials in anesthetized and awake, restrained mice. Spontaneous activity of the KO and the wild-type (WT) showed similar content of gamma and slow (0.1–15 Hz) frequencies, but the KO showed a significantly larger decay of synchronization of gamma oscillations with distance. Coronal cuts in the cortex of WT mice decreased synchronization to values similar to the intact KO. The synchronization of the slow oscillation showed little decay with distance in both mice and was largely reduced after coronal cuts. Our results show that the firing properties of inhibitory interneurons are critical for long-range synchronization of gamma oscillations, and emphasize that intrinsic electrophysiological properties of single cells may play a key role in the spatiotemporal characteristics of network activity.

Spike Timing of Lacunosom-Moleculare Targeting Interneurons and CA3 Pyramidal Cells During High-Frequency Network Oscillations In Vitro

2007 ◽  
Vol 98 (1) ◽  
pp. 96-104 ◽  
Author(s):  
Jay Spampanato ◽  
Istvan Mody
Keyword(s):  
High Frequency ◽  
Epileptiform Activity ◽  
Field Potential ◽  
Pyramidal Cells ◽  
Gamma Oscillations ◽  
Spike Timing ◽  
Network Activity ◽  
Network Oscillations ◽  
Ca3 Pyramidal Cells

Network activity in the 200- to 600-Hz range termed high-frequency oscillations (HFOs) has been detected in epileptic tissue from both humans and rodents and may underlie the mechanism of epileptogenesis in experimental rodent models. Slower network oscillations including theta and gamma oscillations as well as ripples are generated by the complex spike timing and interactions between interneurons and pyramidal cells of the hippocampus. We determined the activity of CA3 pyramidal cells, stratum oriens lacunosum-moleculare (O-LM) and s. radiatum lacunosum-moleculare (R-LM) interneurons during HFO in the in vitro low-Mg2+ model of epileptiform activity in GIN mice. In these animals, interneurons can be identified prior to cell-attached recordings by the expression of green-fluorescent protein (GFP). Simultaneous local field potential recordings from s. pyramidale and on-cell recordings of individual interneurons and principal cells revealed three primary firing behaviors of the active cells: 36% of O-LM interneurons and 60% of pyramidal cells fired action potentials at high frequencies during the HFO. R-LM interneurons were biphasic in that they fired at high frequency at the beginning of the HFO but stopped firing before its end. When considering only the highest frequency component of the oscillations most pyramidal cells fired on the rising phase of the oscillation. These data provide evidence for functional distinction during HFOs within otherwise homogeneous groups of O-LM interneurons and pyramidal cells.

Effect of Common Anesthetics on Dendritic Properties in Layer 5 Neocortical Pyramidal Neurons

2008 ◽  
Vol 99 (3) ◽  
pp. 1394-1407 ◽  
Author(s):  
Sarah Potez ◽  
Matthew E. Larkum
Keyword(s):  
High Frequency ◽  
Pyramidal Neurons ◽  
Animal Experiments ◽  
Apical Dendrite ◽  
Network Activity ◽  
Calcium Spikes ◽  
Firing Properties ◽  
The Impact

Understanding the impact of active dendritic properties on network activity in vivo has so far been restricted to studies in anesthetized animals. However, to date no study has been made to determine the direct effect of the anesthetics themselves on dendritic properties. Here, we investigated the effects of three types of anesthetics commonly used for animal experiments (urethane, pentobarbital and ketamine/xylazine). We investigated the generation of calcium spikes, the propagation of action potentials (APs) along the apical dendrite and the somatic firing properties in the presence of anesthetics in vitro using dual somatodendritic whole cell recordings. Calcium spikes were evoked with dendritic current injection and high-frequency trains of APs at the soma. Surprisingly, we found that the direct actions of anesthetics on calcium spikes were very different. Two anesthetics (urethane and pentobarbital) suppressed dendritic calcium spikes in vitro, whereas a mixture of ketamine and xylazine enhanced them. Propagation of spikes along the dendrite was not significantly affected by any of the anesthetics but there were various changes in somatic firing properties that were highly dependent on the anesthetic. Last, we examined the effects of anesthetics on calcium spike initiation and duration in vivo using high-frequency trains of APs generated at the cell body. We found the same anesthetic-dependent direct effects in addition to an overall reduction in dendritic excitability in anesthetized rats with all three anesthetics compared with the slice preparation.

Spontaneous GABAA receptor-mediated inhibitory currents in adult rat somatosensory cortex

1996 ◽  
Vol 75 (4) ◽  
pp. 1573-1588 ◽  
Author(s):  
P. A. Salin ◽  
D. A. Prince
Keyword(s):  
Nmda Receptor ◽  
Receptor Antagonist ◽  
Gabaa Receptor ◽  
Decay Time ◽  
High Frequency ◽  
Pyramidal Cells ◽  
Receptor Activation ◽  
Inhibitory Interneurons ◽  
Adult Rat ◽  
Bath Application

1. Spontaneous inhibitory synaptic currents (sIPSCs) were studied with whole cell voltage-clamp recordings from 131 pyramidal cells in adult rat somatosensory cortical slices. Neurons were intracellulary labeled with biocytin and classified as supragranular (SG, layers 2-3), layer IV (IV), or infragranular (IG, layer V) on the basis of the laminar localization of their somata. Somatic areas were similar for SG, IV, and IG neurons. All identified pyramidal cells generated high-frequency gamma-aminobutyric acid (GABAA) receptor-mediated synaptic events. 2. Bath application of bicuculline blocked the sIPSCs and resulted in a decrease of approximately 0.5 nS in resting conductance and an inward shift in baseline current. 3. sIPSC frequency was significantly lower in SG versus IG or IV neurons, and this difference was accounted for by the occurrence of a higher percentage of bursts of sIPSCs in the IG and IV neurons. 4. Bath application of the alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic (AMPA) receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) decreased the frequency of sIPSCs by 13-21%. By contrast, application of the N-methyl-D-aspartate (NMDA) receptor antagonist D-2-amino-5-phosphonovaleric acid (D-AP5) generally had no effect on spontaneous IPSC frequency, suggesting that AMPA rather than NMDA receptor activation contributed to resting discharge of inhibitory interneurons. 5. Addition of tetrodotoxin (TTX) to the perfusion medium reduced the spontaneous IPSC frequency by approximately 30-55%. The miniature IPSCs (mIPSCs) seen in TTX-containing solutions had a frequency of approximately 10 Hz and an average conductance of 0.42-0.48 nS. 6. The kinetic properties of mIPSCs generated in pyramidal cells of different layers were the same, with the rise times of approximately 0.9 ms and decay time constants of approximately 8 ms at a holding potential of 0 mV. The decay phase of mIPSCs was generally fitted by one exponential and displayed a voltage dependence with an e-fold increase in decay time constant for a every 198-mV depolarization. 7. These results show that there is ongoing spontaneous release of GABA in neocortical slices that gives rise to high-frequency impulse-related and non-impulse-related postsynaptic inhibitory currents. Activation of AMPA receptors on inhibitory interneurons accounts for only a small proportion of the GABAA receptor-mediated events. Judging from the distribution of mIPSC frequencies in neurons of different laminae, there is a relatively uniform distribution of inhibitory synapses throughout the cortex. Tonic activation of GABAA receptors on neocortical pyramidal neurons generates an increase in resting membrane conductance that may play an important role in vivo by preventing the development of hyperexcitability, modulating excitatory synaptic events, and controlling the rate and patterns of spike discharge.

scholarly journals Recruitment of an inhibitory hippocampal network after bursting in a single granule cell

2007 ◽  
Vol 104 (18) ◽  
pp. 7640-7645 ◽  
Author(s):  
Masahiro Mori ◽  
Beat H. Gähwiler ◽  
Urs Gerber
Keyword(s):  
Pyramidal Cell ◽  
Granule Cell ◽  
Mossy Fiber ◽  
Mossy Fibers ◽  
Pyramidal Cells ◽  
Network Activity ◽  
Inhibitory Input ◽  
Inhibitory Interneurons ◽  
Failure Rates ◽  
Ca3 Pyramidal Cells

The hippocampal CA3 area, an associational network implicated in memory function, receives monosynaptic excitatory as well as disynaptic inhibitory input through the mossy-fiber axons of the dentate granule cells. Synapses made by mossy fibers exhibit low release probability, resulting in high failure rates at resting discharge frequencies of 0.1 Hz. In recordings from functionally connected pairs of neurons, burst firing of a granule cell increased the probability of glutamate release onto both CA3 pyramidal cells and inhibitory interneurons, such that subsequent low-frequency stimulation evoked biphasic excitatory/inhibitory responses in a CA3 pyramidal cell, an effect lasting for minutes. Analysis of the unitary connections in the circuit revealed that granule cell bursting caused powerful activation of an inhibitory network, thereby transiently suppressing excitatory input to CA3 pyramidal cells. This phenomenon reflects the high incidence of spike-to-spike transmission at granule cell to interneuron synapses, the numerically much greater targeting by mossy fibers of inhibitory interneurons versus principal cells, and the extensively divergent output of interneurons targeting CA3 pyramidal cells. Thus, mossy-fiber input to CA3 pyramidal cells appears to function in three distinct modes: a resting mode, in which synaptic transmission is ineffectual because of high failure rates; a bursting mode, in which excitation predominates; and a postbursting mode, in which inhibitory input to the CA3 pyramidal cells is greatly enhanced. A mechanism allowing the transient recruitment of inhibitory input may be important for controlling network activity in the highly interconnected CA3 pyramidal cell region.

Gamma Oscillation Model Predicts Intensity Coding by Phase Rather than Frequency

1997 ◽  
Vol 9 (6) ◽  
pp. 1251-1264 ◽  
Author(s):  
Roger D. Traub ◽  
Miles A. Whittington ◽  
John G. R. Jefferys
Keyword(s):  
Pyramidal Cells ◽  
Sensory Stimulation ◽  
Gamma Oscillations ◽  
Feature Binding ◽  
Phase Lag ◽  
Cell Groups ◽  
Phase Lags ◽  
Zero Phase

Gamma-frequency electroencephalogram oscillations may be important for cognitive processes such as feature binding. Gamma oscillations occur in hippocampus in vivo during the theta state, following physiological sharp waves, and after seizures, and they can be evoked in vitro by tetanic stimulation. In neocortex, gamma oscillations occur under conditions of sensory stimulation as well as during sleep. After tetanic or sensory stimulation, oscillations in regions separated by several millimeters or more occur at the same frequency, but with phase lags ranging from less than 1 ms to 10 ms, depending on the conditions of stimulation. We have constructed a distributed network model of pyramidal cells and interneurons, based on a variety of experiments, that accounts for near-zero phase lag synchrony of oscillations over long distances (with axon conduction delays totaling 16 ms or more). Here we show that this same model can also account for fixed positive phase lags between nearby cell groups coexisting with near-zero phase lags between separated cell groups, a phenomenon known to occur in visual cortex. The model achieves this because interneurons fire spike doublets and triplets that have average zero phase difference throughout the network; this provides a temporal framework on which pyramidal cell phase lags can be superimposed, the lag depending on how strongly the pyramidal cells are excited.

scholarly journals Retrograde transport of Akt by a neuronal Rab5-APPL1 endosome

2018 ◽  
Author(s):  
Livia Goto-Silva ◽  
Marisa P. McShane ◽  
Sara Salinas ◽  
Yannis Kalaidzidis ◽  
Giampietro Schiavo ◽  
...  
Keyword(s):  
Long Range ◽  
Critical Role ◽  
Primary Cultures ◽  
Pyramidal Cells ◽  
Retrograde Transport ◽  
Small Gtpase ◽  
Neurotrophin Receptor ◽  
Dependent Manner ◽  
Long Distance ◽  
Hippocampal Pyramidal Cells

AbstractLong-distance axonal trafficking plays a critical role in neuronal function, and transport defects have been linked to neurodegenerative disorders. Various lines of evidence suggest that the small GTPase Rab5 plays a role in neuronal signaling via early endosomal transport. Here, we characterized the motility of Rab5 endosomes in primary cultures of mouse hippocampal pyramidal cells by live-cell imaging and showed that they exhibit bi-directional long-range motility in axons, with a strong bias toward retrograde transport. Characterization of key Rab5 effectors revealed that endogenous Rabankyrin-5, Rabenosyn-5 and APPL1 are all present in axons. Further analysis of APPL1-positive endosomes showed that, similar to Rab5-endosomes, they display more frequent long-range retrograde than anterograde movement, with the endosomal levels of APPL1 correlated with faster retrograde movement. Interestingly, APPL1-endosomes transport the neurotrophin receptor TrkB and mediate retrograde axonal transport of the kinase Akt1. FRET analysis revealed that APPL1 and Akt1 interact in an endocytosis-dependent manner. We conclude that Rab5-APPL1 endosomes exhibit the hallmarks of axonal signaling endosomes to transport Akt1 in hippocampal pyramidal cells.

scholarly journals Regional heterogeneity of developing GABAergic interneuron excitation in vivo

2019 ◽  
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.

scholarly journals Ontogeny of the VIP+ interneuron sensory-motor circuit prior to active whisking

2020 ◽  
Author(s):  
Cristiana Vagnoni ◽  
Liad J. Baruchin ◽  
Filippo Ghezzi ◽  
Sara Ratti ◽  
Zoltán Molnár ◽  
...  
Keyword(s):  
Long Range ◽  
Critical Role ◽  
Pyramidal Cells ◽  
Cortical Circuits ◽  
Motor Processing ◽  
Efferent Connections ◽  
Sensory Motor ◽  
Sensory Evoked ◽  
Inside Out

ABSTRACTDevelopment of the cortical circuits for sensory-motor processing require the coordinated integration of both columnar and long-range synaptic connections. To understand how this occurs at the level of individual neurons we have explored the timeline over which vasoactive intestinal peptide (VIP)-expressing interneurons integrate into mouse somatosensory cortex. We find a distinction in emergent long-range anterior-motor and columnar glutamatergic inputs onto layer (L)2 and L3 VIP+ interneurons respectively. In parallel, VIP+ interneurons form efferent connections onto both pyramidal cells and interneurons in the immediate column in an inside-out manner. Cell-autonomous deletion of the fate-determinant transcription factor, Prox1, spares long-range anterior-motor inputs onto VIP+ interneurons, but leads to deficits in local connectivity. This imbalance in the somatosensory circuit results in altered spontaneous and sensory-evoked cortical activity in vivo. This identifies a critical role for VIP+ interneurons, and more broadly interneuron heterogeneity, in formative circuits of neocortex.

scholarly journals A Neural Mass Model to Simulate Different Rhythms in a Cortical Region

2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
M. Zavaglia ◽  
F. Cona ◽  
M. Ursino
Keyword(s):  
Long Range ◽  
Critical Role ◽  
Experimental Studies ◽  
Pyramidal Cells ◽  
Neural Mass Model ◽  
Cortical Region ◽  
Eeg Rhythms ◽  
Mass Model ◽  
Neural Mass ◽  
Neural Populations

An original neural mass model of a cortical region has been used to investigate the origin of EEG rhythms. The model consists of four interconnected neural populations: pyramidal cells, excitatory interneurons and inhibitory interneurons with slow and fast synaptic kinetics, and respectively. A new aspect, not present in previous versions, consists in the inclusion of a self-loop among interneurons. The connectivity parameters among neural populations have been changed in order to reproduce different EEG rhythms. Moreover, two cortical regions have been connected by using different typologies of long range connections. Results show that the model of a single cortical region is able to simulate the occurrence of multiple power spectral density (PSD) peaks; in particular the new inhibitory loop seems to have a critical role in the activation in gamma () band, in agreement with experimental studies. Moreover the effect of different kinds of connections between two regions has been investigated, suggesting that long range connections toward interneurons have a major impact than connections toward pyramidal cells. The model can be of value to gain a deeper insight into mechanisms involved in the generation of rhythms and to provide better understanding of cortical EEG spectra.

scholarly journals Evidence that PV+ cells enhance temporal population codes but not stimulus-related timing in auditory cortex

2017 ◽  
Author(s):  
Bryan M. Krause ◽  
Caitlin A. Murphy ◽  
Daniel J. Uhlrich ◽  
Matthew I. Banks
Keyword(s):  
Brain Slices ◽  
Pyramidal Cells ◽  
Gamma Oscillations ◽  
Cortical Activity ◽  
Spike Timing ◽  
Network Activity ◽  
Local Network ◽  
Network Bursts ◽  
Spatio Temporal

AbstractSpatio-temporal cortical activity patterns relative to both peripheral input and local network activity carry information about stimulus identity and context. GABAergic interneurons are reported to regulate spiking at millisecond precision in response to sensory stimulation and during gamma oscillations; their role in regulating spike timing during induced network bursts is unclear. We investigated this issue in murine auditory thalamo-cortical (TC) brain slices, in which TC afferents induced network bursts similar to previous reports in vivo. Spike timing relative to TC afferent stimulation during bursts was poor in pyramidal cells and SOM+ interneurons. It was more precise in PV+ interneurons, consistent with their reported contribution to spiking precision in pyramidal cells. Optogenetic suppression of PV+ cells unexpectedly improved afferent-locked spike timing in pyramidal cells. In contrast, our evidence suggests that PV+ cells do regulate the spatio-temporal spike pattern of pyramidal cells during network bursts, whose organization is suited to ensemble coding of stimulus information. Simulations showed that suppressing PV+ cells reduces the capacity of pyramidal cell networks to produce discriminable spike patterns. By dissociating temporal precision with respect to a stimulus versus internal cortical activity, we identified a novel role for GABAergic cells in regulating information processing in cortical networks.

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