Expression of channelrhodopsin-2 localized within the deep CA1 hippocampal sublayer in the Thy1 line 18 mouse

Dobbins, Dorothy L.; Klorig, David C.; Smith, Thuy K.; Godwin, Dwayne W.

doi:10.1016/j.brainres.2017.11.025

Cited by 13 publications

(11 citation statements)

References 39 publications

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“…We used Calb1-cre mice injected with an adeno-associated virus (AAV5) to restrict expression of channelrhodopsin2 (ChR2) and the yellow fluorescent protein (YFP) in a subset of superficial CA1 cells (30% of Calbindin+ cells were YFP+), whereas deep cells were targeted in the transgenic line Thy1-ChR2 (ref. 28 ) (75% of Calbindin− cells). Using integrated micro-light-emitting diode (LED) optoelectrodes, we exploited nanowatt blue light stimulation for controlled opto-tagging of deep and superficial cells 29 .…”

Section: Resultsmentioning

confidence: 99%

Multimodal determinants of phase-locked dynamics across deep-superficial hippocampal sublayers during theta oscillations

et al. 2020

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Theta oscillations play a major role in temporarily defining the hippocampal rate code by translating behavioral sequences into neuronal representations. However, mechanisms constraining phase timing and cell-type-specific phase preference are unknown. Here, we employ computational models tuned with evolutionary algorithms to evaluate phase preference of individual CA1 pyramidal cells recorded in mice and rats not engaged in any particular memory task. We applied unbiased and hypothesis-free approaches to identify effects of intrinsic and synaptic factors, as well as cell morphology, in determining phase preference. We found that perisomatic inhibition delivered by complementary populations of basket cells interacts with input pathways to shape phase-locked specificity of deep and superficial pyramidal cells. Somatodendritic integration of fluctuating glutamatergic inputs defined cycle-by-cycle by unsupervised methods demonstrated that firing selection is tuneable across sublayers. Our data identify different mechanisms of phase-locking selectivity that are instrumental for flexible dynamical representations of theta sequences.

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Section: Resultsmentioning

confidence: 99%

Multimodal determinants of phase-locked dynamics across deep-superficial hippocampal sublayers during theta oscillations

et al. 2020

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“…We present the results of the oADT experiments first in order to provide context for the oPDT, but it should be noted that prior ADs, and/or behavioral seizures exposure, are not required to obtain oPDT measurements. (Dobbins et al, 2018). 63x oil immersion confocal image.…”

Section: Resultsmentioning

confidence: 99%

“…Thy1 line 18 mice express wildtype ChR2 fused to EYFP in area CA1, subiculum, and layer 5 of cortex (Arenkiel et al, 2007). In area CA1, expression is specific to excitatory pyramidal neurons and is concentrated in calbindin-negative cells in the deep pyramidal cell sublayer (Dobbins et al, 2018). These mice can be bred as homozygotes, ensuring consistent expression levels and patterns from animal to animal, a significant advantage for reproducibility.…”

Section: Methodsmentioning

confidence: 99%

Optogenetically-Induced Population Discharge Threshold as a Sensitive Measure of Network Excitability

Klorig

Alberto

Smith

et al. 2019

Preprint

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Network excitability is governed by synaptic efficacy, intrinsic excitability, and the circuitry in which these factors are expressed. The complex interplay between these factors determines how circuits function and, at the extreme, their susceptibility to seizure. We have developed a sensitive, quantitative estimate of network excitability in freely behaving mice using a novel optogenetic intensity-response procedure. Synchronous activation of deep sublayer CA1 pyramidal cells produces abnormal network-wide epileptiform population discharges (PD) that are nearly indistinguishable from spontaneously-occurring interictal spikes. By systematically varying light intensity, and therefore the magnitude of the optogenetically-mediated current, we generated intensity-response curves using the probability of PD as the dependent variable. Manipulations known to increase excitability, such as sub-convulsive doses (20 mg/kg) of the chemoconvulsant pentylenetetrazol (PTZ), produced a leftward shift in the curve compared to baseline. The anti-epileptic drug levetiracetam (40 mk/kg), in combination with PTZ, produced a rightward shift. Optogenetically-induced population discharge threshold (oPDT) baselines were stable over time, suggesting the metric is appropriate for within-subject experimental designs with multiple pharmacological manipulations. Significance StatementAbnormal excitability is associated with a number of neurological disorders, including epilepsy. Excitability can be measured in single cells in vitro, but it is difficult to extrapolate from these values to the functional impact on the associated network. Epileptiform population discharges are network-wide events that represent a distinct transition from normal to abnormal functional modes. We developed a new method that uses light intensity-response curves to precisely determine the threshold for this transition as a surrogate measure of network excitability.

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“…Thy1 line 18 mice express wild-type ChR2 fused to EYFP in area CA1, subiculum (Sub), and layer 5 of cortex (Arenkiel et al, 2007). In area CA1, expression is specific to excitatory pyramidal neurons and is concentrated in calbindin-negative cells in the deep pyramidal cell sublayer (Dobbins et al, 2018). These mice can be bred as homozygotes, ensuring consistent expression levels and patterns from animal to animal, a significant advantage for reproducibility.…”

Section: Methodsmentioning

confidence: 99%

Optogenetically-Induced Population Discharge Threshold as a Sensitive Measure of Network Excitability

Klorig

Alberto

Smith³

et al. 2019

eNeuro

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Network excitability is governed by synaptic efficacy, intrinsic excitability, and the circuitry in which these factors are expressed. The complex interplay between these factors determines how circuits function and, at the extreme, their susceptibility to seizure. We have developed a sensitive, quantitative estimate of network excitability in freely behaving mice using a novel optogenetic intensity-response procedure. Synchronous activation of deep sublayer CA1 pyramidal cells produces abnormal network-wide epileptiform population discharges (PDs) that are nearly indistinguishable from spontaneously-occurring interictal spikes (IISs). By systematically varying light intensity, and therefore the magnitude of the optogenetically-mediated current, we generated intensityresponse curves using the probability of PD as the dependent variable. Manipulations known to increase excitability, such as sub-convulsive doses (20 mg/kg) of the chemoconvulsant pentylenetetrazol (PTZ), produced a leftward shift in the curve compared to baseline. The anti-epileptic drug levetiracetam (LEV; 40 mk/kg), in combination with PTZ, produced a rightward shift. Optogenetically-induced PD threshold (oPDT) baselines were stable over time, suggesting the metric is appropriate for within-subject experimental designs with multiple pharmacological manipulations.Abnormal excitability is associated with a number of neurologic disorders, including epilepsy. Excitability can be measured in single cells in vitro, but it is difficult to extrapolate from these values to the functional impact on the associated network. Epileptiform population discharges (PDs) are network-wide events that represent a distinct transition from normal to abnormal functional modes. We developed a new method that uses light intensity-response curves to precisely determine the threshold for this transition as a surrogate measure of network excitability.

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Expression of channelrhodopsin-2 localized within the deep CA1 hippocampal sublayer in the Thy1 line 18 mouse

Cited by 13 publications

References 39 publications

Multimodal determinants of phase-locked dynamics across deep-superficial hippocampal sublayers during theta oscillations

Multimodal determinants of phase-locked dynamics across deep-superficial hippocampal sublayers during theta oscillations

Optogenetically-Induced Population Discharge Threshold as a Sensitive Measure of Network Excitability

Optogenetically-Induced Population Discharge Threshold as a Sensitive Measure of Network Excitability

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