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Regulation of sustained attention, false alarm responding and implementation of conditional rules by prefrontal GABAA transmission: comparison with NMDA transmission

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Abstract

Rationale

Both prefrontal cortex (PFC) GABAA and NMDA transmission regulate attentional processes, yet how they may differentially regulate signal detection or other aspects of attention is unclear.

Objectives

We examined PFC GABAA and NMDA receptor regulation of attention using a sustained attention task (SAT) permitting identification of distinct forms of impairments. As this task requires implementation of conditional rules, we also investigated how reducing PFC GABA transmission affected performance of visual and auditory conditional discriminations.

Methods

Male rats were well-trained on the SAT that required identifying whether a brief visual stimulus (500–50 ms) was present/absent by pressing one of two levers. They then received intra-PFC infusions of the GABAA antagonist bicuculline (12.5–50 ng), the NMDA antagonist MK-801 (6 μg), and i.p. injections of MK-801 (0.1–0.3 mg/kg) prior to testing. Separate groups were trained either on a similar task where the visual stimulus was presented for 2.5 s, or a task where presentation of one of two auditory cues required responding on a left or right lever.

Results

Both doses of bicuculline impaired vigilance, selectively increasing errors during nonsignal trials. Intra-PFC MK-801 induced subtle impairments at short signal durations. Systemic MK-801 impaired performance and increased response latencies. Visual and auditory conditional discrimination was impaired by 50 ng, but not 12.5 ng of bicuculline.

Conclusions

These findings highlight a key role for PFC GABA transmission in reducing sensitivity to distractors during attentional performance. Furthermore, they reveal that disruption of GABA signaling can interfere with the ability to implement conditional rules.

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Acknowledgements

This work was supported by a grant from the Canadian Institutes of Health Research (MOP 130393) to SBF. We are grateful to Dr. Rouba Kozak for providing us with the MED-PC codes used for the attention task used in this study.

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  1. Department of Psychology and Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, V6T 1Z4, Canada

    Meagan L. Auger, Juliet Meccia & Stan B. Floresco

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  1. Meagan L. Auger
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  2. Juliet Meccia
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  3. Stan B. Floresco
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Correspondence to Stan B. Floresco.

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Auger, M.L., Meccia, J. & Floresco, S.B. Regulation of sustained attention, false alarm responding and implementation of conditional rules by prefrontal GABAA transmission: comparison with NMDA transmission. Psychopharmacology 234, 2777–2792 (2017). https://doi.org/10.1007/s00213-017-4670-1

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