Abstract
Alterations in neural synchrony and oscillations may contribute to the pathophysiology of schizophrenia and reflect aberrations in cortical glutamatergic and GABAergic neurotransmission. We tested the effects of a GABA agonist and an NMDA antagonist on auditory steady state responses (ASSRs) in awake rats with neonatal ventral hippocampal lesions (NVHLs) as a neurodevelopmental model of schizophrenia. NVHL vs. SHAM lesioned rats were injected with saline then either ketamine (NMDA antagonist) or muscimol (GABAA agonist). Time-frequency analyses examined alterations in phase locking (consistency) across trials and changes in total power (magnitude). ASSRs were compared at five stimulation frequencies (10, 20, 30, 40, and 50Hz). In SHAM rats, phase locking and power generally increased with stimulation frequency. Both ketamine and muscimol also increased phase locking and power in SHAM rats, but mostly in the 20 to 40Hz range. NVHL and ketamine altered the frequency dependence of phase locking, while only ketamine changed power frequency dependence. Muscimol affected power, but not phase locking, in the NVHL rats. NVHL and ketamine models of schizophrenia produce similar independent effects on ASSR, potentially representing similar forms of cortical network/glutamatergic dysfunction, albeit the effects of ketamine were more robust. Muscimol produced NVHL-dependent reductions in ASSR measures, suggesting that cortical networks in this model are intolerant to post-synaptic GABAergic stimulation. These findings suggest the utility of combining lesion, pharmacological, and ASSR approaches in understanding neural mechanisms underlying disturbed synchrony in schizophrenia.
| Original language | English |
|---|---|
| Pages (from-to) | 136-142 |
| Number of pages | 7 |
| Journal | International Journal of Psychophysiology |
| Volume | 86 |
| Issue number | 2 |
| DOIs | |
| State | Published - Nov 2012 |
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Keywords
- ASSRs
- GABA
- NMDA
- NVHL
- Schizophrenia
- Synchronization
ASJC Scopus subject areas
- Neuroscience(all)
- Physiology (medical)
- Neuropsychology and Physiological Psychology
Cite this
Auditory steady state responses in a schizophrenia rat model probed by excitatory/inhibitory receptor manipulation. / Vohs, Jenifer; Chambers, R.; O'Donnell, Brian; Krishnan, Giri P.; Morzorati, Sandra.
In: International Journal of Psychophysiology, Vol. 86, No. 2, 11.2012, p. 136-142.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Auditory steady state responses in a schizophrenia rat model probed by excitatory/inhibitory receptor manipulation
AU - Vohs, Jenifer
AU - Chambers, R.
AU - O'Donnell, Brian
AU - Krishnan, Giri P.
AU - Morzorati, Sandra
PY - 2012/11
Y1 - 2012/11
N2 - Alterations in neural synchrony and oscillations may contribute to the pathophysiology of schizophrenia and reflect aberrations in cortical glutamatergic and GABAergic neurotransmission. We tested the effects of a GABA agonist and an NMDA antagonist on auditory steady state responses (ASSRs) in awake rats with neonatal ventral hippocampal lesions (NVHLs) as a neurodevelopmental model of schizophrenia. NVHL vs. SHAM lesioned rats were injected with saline then either ketamine (NMDA antagonist) or muscimol (GABAA agonist). Time-frequency analyses examined alterations in phase locking (consistency) across trials and changes in total power (magnitude). ASSRs were compared at five stimulation frequencies (10, 20, 30, 40, and 50Hz). In SHAM rats, phase locking and power generally increased with stimulation frequency. Both ketamine and muscimol also increased phase locking and power in SHAM rats, but mostly in the 20 to 40Hz range. NVHL and ketamine altered the frequency dependence of phase locking, while only ketamine changed power frequency dependence. Muscimol affected power, but not phase locking, in the NVHL rats. NVHL and ketamine models of schizophrenia produce similar independent effects on ASSR, potentially representing similar forms of cortical network/glutamatergic dysfunction, albeit the effects of ketamine were more robust. Muscimol produced NVHL-dependent reductions in ASSR measures, suggesting that cortical networks in this model are intolerant to post-synaptic GABAergic stimulation. These findings suggest the utility of combining lesion, pharmacological, and ASSR approaches in understanding neural mechanisms underlying disturbed synchrony in schizophrenia.
AB - Alterations in neural synchrony and oscillations may contribute to the pathophysiology of schizophrenia and reflect aberrations in cortical glutamatergic and GABAergic neurotransmission. We tested the effects of a GABA agonist and an NMDA antagonist on auditory steady state responses (ASSRs) in awake rats with neonatal ventral hippocampal lesions (NVHLs) as a neurodevelopmental model of schizophrenia. NVHL vs. SHAM lesioned rats were injected with saline then either ketamine (NMDA antagonist) or muscimol (GABAA agonist). Time-frequency analyses examined alterations in phase locking (consistency) across trials and changes in total power (magnitude). ASSRs were compared at five stimulation frequencies (10, 20, 30, 40, and 50Hz). In SHAM rats, phase locking and power generally increased with stimulation frequency. Both ketamine and muscimol also increased phase locking and power in SHAM rats, but mostly in the 20 to 40Hz range. NVHL and ketamine altered the frequency dependence of phase locking, while only ketamine changed power frequency dependence. Muscimol affected power, but not phase locking, in the NVHL rats. NVHL and ketamine models of schizophrenia produce similar independent effects on ASSR, potentially representing similar forms of cortical network/glutamatergic dysfunction, albeit the effects of ketamine were more robust. Muscimol produced NVHL-dependent reductions in ASSR measures, suggesting that cortical networks in this model are intolerant to post-synaptic GABAergic stimulation. These findings suggest the utility of combining lesion, pharmacological, and ASSR approaches in understanding neural mechanisms underlying disturbed synchrony in schizophrenia.
KW - ASSRs
KW - GABA
KW - NMDA
KW - NVHL
KW - Schizophrenia
KW - Synchronization
UR - http://www.scopus.com/inward/record.url?scp=84869097616&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84869097616&partnerID=8YFLogxK
U2 - 10.1016/j.ijpsycho.2012.04.002
DO - 10.1016/j.ijpsycho.2012.04.002
M3 - Article
C2 - 22504207
AN - SCOPUS:84869097616
VL - 86
SP - 136
EP - 142
JO - International Journal of Psychophysiology
JF - International Journal of Psychophysiology
SN - 0167-8760
IS - 2
ER -