Spared motivational modulation of cognitive effort in a maternal immune activation model of schizophrenia risk.

Abstract

Maternal immune activation (MIA) during gestation is a significant risk factor for development of schizophrenia and other neurodevelopmental diseases. In animal models of this risk factor, MIA during pregnancy can produce offspring that recapitulate certain aspects of the behavioral and neurophysiological impairments seen in schizophrenia. Here, the authors tested the effect of polyinosinic-polycytidylic acid (poly I:C)-induced MIA in a task that explicitly assays the interaction between motivation and cognition. In our paradigm, discrimination accuracy during a sustained-attention task is differentially impacted by environmental cues that signal the probability of reward for accurate performance. Cognition-motivation interactions are implicated in producing functional impairments in patients. Therefore, to the extent that this MIA model recapitulates such impairments, the authors predicted impaired ability of reward-associated signals to modulate cognitive performance in MIA rat offpsring. Adult offspring of dams in which MIA was induced displayed impaired prepulse inhibition relative to controls, verifying a functional effect of poly I:C induction. Despite this deficit, there were no differences between MIA and control rats in any aspects of task learning or performance, including under extinction and reacquisition conditions. These results indicate that MIA spares functioning of some of the cognitive, motivational, and decision-making processes that are impacted in schizophrenia and suggest that MIA as an isolated manipulation does not model the full range and nuance of the cognitive and motivational impairments in the disease. The authors suggest that some aspects of the functional impairment in schizophrenia and other neurodevelopmental diseases may be better modeled using multiple "hit" models of disease risk. (PsycINFO Database Record

Maternal immune activation: reporting guidelines to improve the rigor, reproducibility, and transparency of the model

“…20-30°C), the more robust (i.e., longer-lasting) effect of high-dose Poly IC is hypothermia [68]. Similar to behavioral symptoms seen in individuals with schizophrenia and ASD, offspring that were prenatally treated with Poly IC have been reported to have significant abnormalities in several behaviors, including deficits in the pre-pulse inhibition [62,63,[69][70][71], acoustic startle response, decreases in exploratory behavior in both open-field and novel-object tests, increased immobility in the forced swim test, and decreases in social interactions and sucrose/saccharine preferences [64,[72][73][74][75][76][77][78][79][80][81][82]. Importantly, many of these effects are dependent on the prenatal timing, Poly IC dosing, and genetic background of animals.…”

Gestational poly(I:C) attenuates, not exacerbates, the behavioral, cytokine and mTOR changes caused by isolation rearing in a rat ‘dual-hit’ model for neurodevelopmental disorders

“…However, it is becoming increasingly clear that such models are variable, subject to PIC batch effects (Careaga et al, 2018;Kowash et al, 2019;Mueller et al, 2019), and at least in some laboratories do not adequately model the full range of cognitive or motivational impairments seen in patients (Bates et al, 2018;Gray et al, 2019).…”

“…It has been suggested that combining separate neurodevelopmental interventions, like MIA and isolation rearing, into a dual-hit model might overcome some of their individual limitations (Bates et al, 2018;Shortall et al, 2018). Crucially it appears that even subclinical MIA can increase vulnerability of the offspring to a second hit, thus increasing the likelihood of environmental stressors causing a schizophrenia-or ASD-like phenotype (Estes and McAllister, 2016).…”

Basal Forebrain Mediates Motivational Recruitment of Attention by Reward-Associated Cues

“…To study the interaction between motivation and attention, we developed the Signaled Probability Sustained Attention (SPSA; Figure 1 ) task ( Ward et al, 2015a , b ; Hall-McMaster et al, 2017 ; Bates et al, 2018 ). In this prefrontal-dependent sustained-attention task ( Kahn et al, 2012 ) rats must attend to cues that signal which of two responses will be rewarded on each trial.…”