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Translational utility of rodent hippocampal auditory gating in schizophrenia research: a review and evaluation.

Smucny J, Stevens KE, Olincy A, Tregellas JR - Transl Psychiatry (2015)

Bottom Line: We show that drug effects on the P20-N40 are highly predictive of human effects across similar dose ranges.Furthermore, mental status (for example, anesthetized vs alert) does not appear to diminish the predictive capacity of these recordings.We then discuss hypothesized neuropharmacologic mechanisms that may underlie gating effects for each drug studied.

View Article: PubMed Central - PubMed

Affiliation: 1] Neuroscience Program, University of Colorado Anschutz Medical Campus, Aurora, CO, USA [2] Research Service, Denver VA Medical Center, Denver, CO, USA [3] Department of Psychiatry, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

ABSTRACT
Impaired gating of the auditory evoked P50 potential is one of the most pharmacologically well-characterized features of schizophrenia. This deficit is most commonly modeled in rodents by implanted electrode recordings from the hippocampus of the rodent analog of the P50, the P20-N40. The validity and effectiveness of this tool, however, has not been systematically reviewed. Here, we summarize findings from studies that have examined the effects of pharmacologic modulation on gating of the rodent hippocampal P20-N40 and the human P50. We show that drug effects on the P20-N40 are highly predictive of human effects across similar dose ranges. Furthermore, mental status (for example, anesthetized vs alert) does not appear to diminish the predictive capacity of these recordings. We then discuss hypothesized neuropharmacologic mechanisms that may underlie gating effects for each drug studied. Overall, this review supports continued use of hippocampal P20-N40 gating as a translational tool for schizophrenia research.

No MeSH data available.


Related in: MedlinePlus

Comparison of S1 waveforms, S2 waveforms and S2/S1 ratios during placebo/saline and DMXB-A administration as measured by EEG in a schizophrenia patient (adapted from Olincy et al.25) and an implanted electrode in the CA3 subfield of the DBA/2 mouse hippocampus (adapted from Simosky et al.26). Positive polarity is downwards. Vertical hash marks denote the P50 in the patient and the P20–N40 in the mouse. Similar improvements on sensory gating were observed after DMXB-A treatment in both patients and mice. DMXB-A, 3-2,4 dimethoxybenzylidene anabaseine; EEG, electroencephalography.
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fig4: Comparison of S1 waveforms, S2 waveforms and S2/S1 ratios during placebo/saline and DMXB-A administration as measured by EEG in a schizophrenia patient (adapted from Olincy et al.25) and an implanted electrode in the CA3 subfield of the DBA/2 mouse hippocampus (adapted from Simosky et al.26). Positive polarity is downwards. Vertical hash marks denote the P50 in the patient and the P20–N40 in the mouse. Similar improvements on sensory gating were observed after DMXB-A treatment in both patients and mice. DMXB-A, 3-2,4 dimethoxybenzylidene anabaseine; EEG, electroencephalography.

Mentions: Representative P50 and P20–N40 waveforms taken from the vertex electrode of a human subject and from an electrode implanted in the hippocampus of a mouse (respectively) are shown in Figure 4.


Translational utility of rodent hippocampal auditory gating in schizophrenia research: a review and evaluation.

Smucny J, Stevens KE, Olincy A, Tregellas JR - Transl Psychiatry (2015)

Comparison of S1 waveforms, S2 waveforms and S2/S1 ratios during placebo/saline and DMXB-A administration as measured by EEG in a schizophrenia patient (adapted from Olincy et al.25) and an implanted electrode in the CA3 subfield of the DBA/2 mouse hippocampus (adapted from Simosky et al.26). Positive polarity is downwards. Vertical hash marks denote the P50 in the patient and the P20–N40 in the mouse. Similar improvements on sensory gating were observed after DMXB-A treatment in both patients and mice. DMXB-A, 3-2,4 dimethoxybenzylidene anabaseine; EEG, electroencephalography.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4490287&req=5

fig4: Comparison of S1 waveforms, S2 waveforms and S2/S1 ratios during placebo/saline and DMXB-A administration as measured by EEG in a schizophrenia patient (adapted from Olincy et al.25) and an implanted electrode in the CA3 subfield of the DBA/2 mouse hippocampus (adapted from Simosky et al.26). Positive polarity is downwards. Vertical hash marks denote the P50 in the patient and the P20–N40 in the mouse. Similar improvements on sensory gating were observed after DMXB-A treatment in both patients and mice. DMXB-A, 3-2,4 dimethoxybenzylidene anabaseine; EEG, electroencephalography.
Mentions: Representative P50 and P20–N40 waveforms taken from the vertex electrode of a human subject and from an electrode implanted in the hippocampus of a mouse (respectively) are shown in Figure 4.

Bottom Line: We show that drug effects on the P20-N40 are highly predictive of human effects across similar dose ranges.Furthermore, mental status (for example, anesthetized vs alert) does not appear to diminish the predictive capacity of these recordings.We then discuss hypothesized neuropharmacologic mechanisms that may underlie gating effects for each drug studied.

View Article: PubMed Central - PubMed

Affiliation: 1] Neuroscience Program, University of Colorado Anschutz Medical Campus, Aurora, CO, USA [2] Research Service, Denver VA Medical Center, Denver, CO, USA [3] Department of Psychiatry, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

ABSTRACT
Impaired gating of the auditory evoked P50 potential is one of the most pharmacologically well-characterized features of schizophrenia. This deficit is most commonly modeled in rodents by implanted electrode recordings from the hippocampus of the rodent analog of the P50, the P20-N40. The validity and effectiveness of this tool, however, has not been systematically reviewed. Here, we summarize findings from studies that have examined the effects of pharmacologic modulation on gating of the rodent hippocampal P20-N40 and the human P50. We show that drug effects on the P20-N40 are highly predictive of human effects across similar dose ranges. Furthermore, mental status (for example, anesthetized vs alert) does not appear to diminish the predictive capacity of these recordings. We then discuss hypothesized neuropharmacologic mechanisms that may underlie gating effects for each drug studied. Overall, this review supports continued use of hippocampal P20-N40 gating as a translational tool for schizophrenia research.

No MeSH data available.


Related in: MedlinePlus