Regulation of sustained attention, false alarm responding
and implementation of conditional rules by prefrontal GABA
transmission: comparison with NMDA transmission
Meagan L. Auger
Stan B. Floresco
Received: 1 March 2017 / Accepted: 8 June 2017 /Published online: 24 June 2017
Springer-Verlag GmbH Germany 2017
Rationale Both prefrontal cortex (PFC) GABA
transmission regulate attentional processes, yet how they may
differentially regulate signal detection or other aspects of at-
tention is unclear.
Objectives We examined PFC GABA
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 re-
ceived intra-PFC infusions of the GABA
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, selec-
tively 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 discrimi-
nation 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 dur-
ing attentional performance. Furthermore, they reveal that dis-
ruption of GABA signaling can interfere with the ability to
implement conditional rules.
Attention encompasses a collection of cognitive operations
that influence the detection of sensory stimuli and whether
they are selected for higher-level processing. These operations
include selective attention, divided attention and sustained
attention, or vigilance. Vigilance refers to the ability to remain
in a state of readiness to detect and respond to incoming stim-
uli that appear rarely and unexpectedly (Parasuraman et al.
1998). Impairments in attentional processes, including vigi-
lance, are a core cognitive feature of many psychiatric disor-
ders, including attention deficit hyperactive disorder (Huang-
Pollock et al. 2012), schizophrenia (Cornblatt and Malhotra
2001; Liu et al. 2002), and bipolar disorder (Hegerl et al.
2010; Marotta et al. 2015). Furthermore, the ability to direct
attention is often a necessary component process for more
complex cognitive operations, such as working memory
(Gazzaley and Nobre 2012), and may, therefore, partially ac-
count for deficits in higher order cognition observed in these
Vigilance and other attentional processes are thought to be
mediated by networks of brain regions that include the pre-
frontal and parietal cortices (Petersen and Posner 2012).
Electronic supplementary material The online version of this article
(doi:10.1007/s00213-017-4670-1) contains supplementary material,
which is available to authorized users.
* Stan B. Floresco
Department of Psychology and Djavad Mowafaghian Centre for
Brain Health, University of British Columbia, Vancouver, BC V6T
Psychopharmacology (2017) 234:2777–2792