Abstract
Ultrasound is a promising neural stimulation modality, but an incomplete understanding of its range and mechanism of effect limits its therapeutic application. We investigated the modulation of spontaneous hippocampal spike activity by ultrasound at a lower acoustic intensity and longer time scale than has been previously attempted, hypothesizing that spiking would change conditionally upon the availability of glutamate receptors. Using a 60-channel multielectrode array (MEA), we measured spontaneous spiking across organotypic rat hippocampal slice cultures (N=28) for 3min each before, during, and after stimulation with low-intensity unfocused pulsed or sham ultrasound (spatial-peak pulse average intensity 780μW/cm2) preperfused with artificial cerebrospinal fluid, 300μM kynurenic acid (KA), or 0.5μM tetrodotoxin (TTX) at 3ml/min. Spike rates were normalized and compared across stimulation type and period, subregion, threshold level, and/or perfusion condition using repeated-measures ANOVA and generalized linear mixed models. Normalized 3-min spike counts for large but not midsized, small, or total spikes increased after but not during ultrasound relative to sham stimulation. This result was recapitulated in subregions CA1 and dentate gyrus and replicated in a separate experiment for all spike size groups in slices pretreated with aCSF but not KA or TTX. Increases in normalized 18-sec total, midsized, and large spike counts peaked predominantly 1.5min following ultrasound stimulation. Our low-intensity ultrasound setup exerted delayed glutamate receptor-dependent, amplitude- and possibly region-specific influences on spontaneous spike rates across the hippocampus, expanding the range of known parameters at which ultrasound may be used for neural activity modulation.
| Original language | English |
|---|---|
| Journal | Journal of Neuroscience Research |
| DOIs | |
| Publication status | Accepted/In press - 2016 |
| Externally published | Yes |
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Keywords
- Electrophysiology
- Hippocampus
- Multielectrode array
- Spike detection
- Spontaneous activity
- Unfocused pulsed ultrasound
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience
Cite this
Prolonged stimulation with low-intensity ultrasound induces delayed increases in spontaneous hippocampal culture spiking activity. / Kim, Hyun Bum; Swanberg, Kelley M.; Han, Hee Sok; Kim, Jung Chae; Kim, Jun Woo; Lee, Sungon; Lee, Changjoon; Maeng, Sungho; Kim, Tae Seong; Park, Ji Ho.
In: Journal of Neuroscience Research, 2016.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Prolonged stimulation with low-intensity ultrasound induces delayed increases in spontaneous hippocampal culture spiking activity
AU - Kim, Hyun Bum
AU - Swanberg, Kelley M.
AU - Han, Hee Sok
AU - Kim, Jung Chae
AU - Kim, Jun Woo
AU - Lee, Sungon
AU - Lee, Changjoon
AU - Maeng, Sungho
AU - Kim, Tae Seong
AU - Park, Ji Ho
PY - 2016
Y1 - 2016
N2 - Ultrasound is a promising neural stimulation modality, but an incomplete understanding of its range and mechanism of effect limits its therapeutic application. We investigated the modulation of spontaneous hippocampal spike activity by ultrasound at a lower acoustic intensity and longer time scale than has been previously attempted, hypothesizing that spiking would change conditionally upon the availability of glutamate receptors. Using a 60-channel multielectrode array (MEA), we measured spontaneous spiking across organotypic rat hippocampal slice cultures (N=28) for 3min each before, during, and after stimulation with low-intensity unfocused pulsed or sham ultrasound (spatial-peak pulse average intensity 780μW/cm2) preperfused with artificial cerebrospinal fluid, 300μM kynurenic acid (KA), or 0.5μM tetrodotoxin (TTX) at 3ml/min. Spike rates were normalized and compared across stimulation type and period, subregion, threshold level, and/or perfusion condition using repeated-measures ANOVA and generalized linear mixed models. Normalized 3-min spike counts for large but not midsized, small, or total spikes increased after but not during ultrasound relative to sham stimulation. This result was recapitulated in subregions CA1 and dentate gyrus and replicated in a separate experiment for all spike size groups in slices pretreated with aCSF but not KA or TTX. Increases in normalized 18-sec total, midsized, and large spike counts peaked predominantly 1.5min following ultrasound stimulation. Our low-intensity ultrasound setup exerted delayed glutamate receptor-dependent, amplitude- and possibly region-specific influences on spontaneous spike rates across the hippocampus, expanding the range of known parameters at which ultrasound may be used for neural activity modulation.
AB - Ultrasound is a promising neural stimulation modality, but an incomplete understanding of its range and mechanism of effect limits its therapeutic application. We investigated the modulation of spontaneous hippocampal spike activity by ultrasound at a lower acoustic intensity and longer time scale than has been previously attempted, hypothesizing that spiking would change conditionally upon the availability of glutamate receptors. Using a 60-channel multielectrode array (MEA), we measured spontaneous spiking across organotypic rat hippocampal slice cultures (N=28) for 3min each before, during, and after stimulation with low-intensity unfocused pulsed or sham ultrasound (spatial-peak pulse average intensity 780μW/cm2) preperfused with artificial cerebrospinal fluid, 300μM kynurenic acid (KA), or 0.5μM tetrodotoxin (TTX) at 3ml/min. Spike rates were normalized and compared across stimulation type and period, subregion, threshold level, and/or perfusion condition using repeated-measures ANOVA and generalized linear mixed models. Normalized 3-min spike counts for large but not midsized, small, or total spikes increased after but not during ultrasound relative to sham stimulation. This result was recapitulated in subregions CA1 and dentate gyrus and replicated in a separate experiment for all spike size groups in slices pretreated with aCSF but not KA or TTX. Increases in normalized 18-sec total, midsized, and large spike counts peaked predominantly 1.5min following ultrasound stimulation. Our low-intensity ultrasound setup exerted delayed glutamate receptor-dependent, amplitude- and possibly region-specific influences on spontaneous spike rates across the hippocampus, expanding the range of known parameters at which ultrasound may be used for neural activity modulation.
KW - Electrophysiology
KW - Hippocampus
KW - Multielectrode array
KW - Spike detection
KW - Spontaneous activity
KW - Unfocused pulsed ultrasound
UR - http://www.scopus.com/inward/record.url?scp=84979787267&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84979787267&partnerID=8YFLogxK
U2 - 10.1002/jnr.23845
DO - 10.1002/jnr.23845
M3 - Article
C2 - 27465511
AN - SCOPUS:84979787267
JO - Journal of Neuroscience Research
JF - Journal of Neuroscience Research
SN - 0360-4012
ER -