Biomedical subjects

Yuling Liang

Publications and source records attributed to Yuling Liang.

7 recordsLinked to original sources

PubMed2006

Effects of nicotine vary across two auditory evoked potentials in the mouse.

BACKGROUND: Schizophrenia patients display sensory processing deficits, reduced alpha7-nicotine receptor expression, and increased incidence of smoking, prompting investigation of nicotine receptor agonists as possible treatments. We evaluated the effects of acute and chronic nicotine, using an animal model that incorporates genetic variation for sensory processing and nicotine sensitivity. METHODS: C57BL/6J and DBA/2Hsd mice received 2 weeks of 4.2 mg/kg chronic nicotine or saline. Auditory evoked potentials were recorded before and after acute nicotine injection of 1.05 mg/kg on day 14, with a paired-click paradigm (S1/S2). Amplitude and gating of the P20 and N40 were compared between conditions. RESULTS: Acute nicotine increased the amplitude and gating of the P20 and decreased the amplitude and gating of the N40 across all groups, primarily by acting on S1. Chronic nicotine attenuated the effects of acute nicotine on the N40. CONCLUSIONS: Our data support the notion that the mouse P20 shares pharmacological response properties with the human P50. In addition, findings suggest that nicotine might increase the initial sensory response (S1), with a resulting improvement in gating of some components.

Acoustic Stimulation↗

PubMed2006

Corticosterone modulates auditory gating in mouse.

Previous studies suggest that circulating glucocorticoids may influence the encoding and processing of sensory stimuli. The current study investigated this hypothesis by measuring the generation (amplitude), gating (recovery cycle), and sensitivity (intensity function) of auditory evoked responses in C57BL/6 mice treated with chronic corticosterone (0, 1, 5, 15, or 30 mg/kg/day for 14 days). We found that low-dose corticosterone (5 but not 1 mg/kg/day) enhanced the amplitude and improved gating of evoked potentials without affecting the intensity function. In comparison, higher doses (15 and 30 mg/kg/day) decreased the amplitude and impaired gating of evoked potentials, also without altering the stimulus intensity function. At all doses, lower amplitudes of evoked potentials were significantly correlated with higher circulating corticosterone levels. These data highlight the need to consider serum glucocorticoid levels when assessing human disease states associated with aberrations of information processing such as schizophrenia and depression.

Animals↗

PubMed2005

Ketamine produces lasting disruptions in encoding of sensory stimuli.

The current study analyzed the acute, chronic, and lasting effects of ketamine administration in four inbred mouse strains (C3H/HeHsd, C57BL/6Hsd, FVB/Hsd, and DBA/2Hsd) to evaluate vulnerability to ketamine as a drug of abuse and as a model of schizophrenia. Serum half-life of ketamine was similar between all strains (approximately 13 min). Also, the ratio of brain-to-serum ketamine levels was 3:1. Examination of multiple phases of auditory processing using auditory-evoked potentials (AEPs) following acute ketamine (0, 5, and 20 mg/kg) treatment revealed C3H/HeHsd mice to be most vulnerable to ketamine-induced alterations in AEPs, whereas FVB/Hsd mice exhibited the least electrophysiological sensitivity to ketamine. Overall, the precortical P1-evoked potential component increased in amplitude and latency, whereas the cortically generated N1 and P2 components decreased in amplitude and latency following acute ketamine across all strains. Brain catecholamine analyses indicated that ketamine decreased hippocampus epinephrine levels in C3H/HeHsd but elevated hippocampus epinephrine levels in FVB/Hsd, suggesting one potential mechanism for AEP vulnerability to ketamine. Based on results of the acute study, the immediate and lasting effects of chronic low-dose ketamine on AEPs were examined among C3H/HeHsd (sensitive) and FVB/Hsd (insensitive) mice. We observed a decrement of the N1 amplitude that persisted at least 1 week after the last exposure to ketamine across both strains. This lasting deficit in information processing occurred in the absence of acute changes among the FVB/Hsd mice. Implications for both ketamine abuse and N-methyl-D-aspartate hypofunction models of schizophrenia are discussed.

Anesthetics, Dissociative↗

PubMed2004

The effects of ketamine vary among inbred mouse strains and mimic schizophrenia for the P80, but not P20 or N40 auditory ERP components.

N-methyl-D-aspartate (NMDA) antagonists produce behavioral and electrophysiological effects similar to schizophrenia. The mouse P20, N40, and P80 event related potential (ERP) components were analyzed for genetic variance among inbred strains and ketamine-induced differences to model abnormalities in the P50, N100, and P200 in schizophrenia. Ketamine increased P20/N40 amplitude and decreased P80 amplitude. Therefore, the effects of ketamine in mice are inconsistent with alterations in the corresponding P50 and N100 in schizophrenia, suggesting that NMDA receptor dysfunction may not underlie abnormalities of these components in schizophrenia. However, the effects of ketamine on the mouse P80 were consistent with P200 ERP changes in schizophrenia and support the hypothesis that NMDA dysfunction may contribute to some neuronal abnormalities in schizophrenia. The current study lays the groundwork for defining the role of NMDA-mediated transmission for specific aspects of neuronal processing that vary with genetic background. Future studies could use transcription profiling to clarify such interactions between genetic background, specific neuronal circuits, and transmitter systems.

Animals↗

PubMed2004

Effects of chronic olanzapine and haloperidol differ on the mouse N1 auditory evoked potential.

Auditory evoked potentials have been used in a variety of animal models to assess information-processing impairments in schizophrenia. Previous mouse models have primarily employed a paired click paradigm to assess the transient measures of auditory gating. The current study uses stimulus trains at varied interstimulus intervals (ISI) between 0.25 and 8 s in mice to assess the effects of chronic olanzapine and haloperidol on auditory processing. Data indicate that olanzapine increases the amplitude of the N40, P80, and P20/N40 components of the auditory evoked potential, whereas haloperidol had no such effect. The ISI paradigm also allowed for an evaluation of several components of the mouse evoked potential to assess those that display response properties similar to the human P50 and N100. Data suggest that the mouse N40 displays an ISI response relationship that shares characteristics with the human N100, whereas the P20 appears more consistent with the human P50 across the ISI range evaluated in this task. This study suggests that olanzapine may help improve N100 impairments seen in schizophrenia, while haloperidol does not.

Acoustic Stimulation↗

PubMed2003

Inhibition of auditory evoked potentials and prepulse inhibition of startle in DBA/2J and DBA/2Hsd inbred mouse substrains.

Previous data have shown differences among inbred mouse strains in sensory gating of auditory evoked potentials, prepulse inhibition (PPI) of startle, and startle amplitude. These measures of sensory and sensorimotor gating have both been proposed as models for genetic determinants of sensory processing abnormalities in patients with schizophrenia and their first-degree relatives. Data from our laboratory suggest that auditory evoked potentials of DBA/2J mice differ from those previously described for DBA/2Hsd. Therefore, we compared evoked potentials and PPI in these two closely related substrains based on the hypothesis that any observed endophenotypic differences are more likely to distinguish relevant from incidental genetic heterogeneity than similar approaches using inbred strains that vary across the entire genome. We found that DBA/2Hsd substrain exhibited reduced inhibition of evoked potentials and reduced startle relative to the DBA/2J substrain without alterations in auditory sensitivity, amplitude of evoked potentials or PPI of startle. These results suggest that gating of auditory evoked potentials and PPI of startle measure different aspects of neuronal function. The differences between the substrains might reflect genetic drift. Alternatively, differences could arise from different rearing environments or other non-genetic factors. Future studies will attempt to determine the cause of these differences in sensory and sensorimotor processing between these two closely related inbred mouse strains.

Acoustic Stimulation↗

PubMed2002

Effects of strain, novelty, and NMDA blockade on auditory-evoked potentials in mice.

People with schizophrenia exhibit impaired ability to modify electroencephalographic event-related potential (ERP) responses to novel stimuli. These deficits serve as a window into the abnormalities of neuronal organization and function and are thought to reflect a component of genetic vulnerability for schizophrenia. We describe differences among inbred mouse strains for ERPs following a novelty detection paradigm, as a model for genetic contributions to disease vulnerability. Auditory-evoked potentials were recorded during an auditory oddball task in nonanesthetized C57BL/6J, C3H/HeJ, and DBA/2J mice prior to and following ketamine (10 mg/kg). Stimuli consisted of 80 sets of 24 standard tones followed by one novel tone. Principal component analysis yielded four temporal components that contribute to the auditory ERP responses to standard and novel stimuli. Two principal components that varied between standard and novel stimuli also differed among inbred mouse strains. Post hoc analyses indicate that strain effects on novelty detection are due to a significant difference between the response to novel and standard tones in C3H/HeJ mice that is absent in the other two strains. Inbred strains of mice vary in their ability to perform neuronal detection of change in the auditory environment. The ability to model novelty detection deficits in mice will aid in identifying genetic contributions to abnormal neuronal organization in people with schizophrenia.

Acoustic Stimulation↗