Sustained Attentional States Require Distinct Temporal Involvement of the Dorsal and Ventral Medial Prefrontal Cortex

Abstract

Attending the sensory environment for cue detection is a cognitive operation that occurs on a time scale of seconds. The dorsal and ventral medial prefrontal cortex (mPFC) contribute to separate aspects of attentional processing. Pyramidal neurons in different parts of the mPFC are active during cognitive behavior, yet whether this activity is causally underlying attentional processing is not known. We aimed to determine the precise temporal requirements for activation of the mPFC subregions during the seconds prior to cue detection. To test this, we used optogenetic silencing of dorsal or ventral mPFC pyramidal neurons at defined time windows during a sustained attentional state. We find that the requirement of ventral mPFC pyramidal neuron activity is strictly time-locked to stimulus detection. Inhibiting the ventral mPFC 2 s before or during cue presentation reduces response accuracy and hampers behavioral inhibition. The requirement for dorsal mPFC activity on the other hand is temporally more loosely related to a preparatory attentional state, and short lapses in pyramidal neuron activity in dorsal mPFC do not affect performance. This only occurs when the dorsal mPFC is inhibited during the entire preparatory period. Together, our results reveal that a dissociable temporal recruitment of ventral and dorsal mPFC is required during attentional processing.

Prefrontal cortical ChAT-VIP interneurons provide local excitation by cholinergic synaptic transmission and control attention

“…within two seconds after the cue light went off). Therefore, in line with previous work 58 , the omission criterion was increased to less than 40% omissions.…”

“…Following virus delivery in rat brain for behavioural experiments, 2 guide screws and 2 chronic implantable glass fibers (200 μm diameter, 0.20 numerical aperture, ThorLabs, Newton, NJ, USA) mounted in a sleeve (1.25 mm diameter; ThorLabs, Newton, NJ, USA) were placed over the Prelimbic mPFC (200-300 μm on average) under a 10° angle 58 . Finally, a double component dental cement (Pulpdent©, Watertown, USA) mixed with black carbon powder (Sigma Aldrich, USA) was used to secure optic fibers.…”

“…After one week of recovery from surgery and 1 week of habituation in the reversed light/dark cycle, rats started training in the 5-CSRTT in operant cages (Med Associates Inc., St. Albans, VT, USA). Training and optical inhibition procedures were analogous to our previously published work with minor adaptations 58 (Supplemental Fig 4). In short, following the initial training phase, progression was based on individual performance of each rat, and was reduced from 16 s to 1 s. Criteria to move to a shortened stimulus duration were the percentage of accuracy (>80%) and omitted trials (<20%).…”

Neural Representation of Motor Output, Context and Behavioral Adaptation in Rat Medial Prefrontal Cortex During Learned Behavior

“…The medial prefrontal cortex (mPFC) integrates and processes a multitude of information streams to drive behavior (Groenewegen and Uylings, 2000 ; Dalley et al, 2004 ; Gruber et al, 2010 ; Euston et al, 2012 ; Luchicchi et al, 2016 ). Activity of mPFC neurons correlates with task outcomes with both positive (Gruber et al, 2010 ; Horst and Laubach, 2013 ; Orsini et al, 2015 ; Pinto and Dan, 2015 ; Amarante et al, 2017 ) and negative valence (Senn et al, 2014 ; Halladay and Blair, 2015 ; Pinto and Dan, 2015 ; Kim et al, 2017 ; Rozeske et al, 2018 ) and distinct populations of mPFC neurons are selectively activated during movement and movement inhibition (Halladay and Blair, 2015 ).…”

The Arctic/Swedish APP mutation alters the impact of chronic stress on cognition in mice

“…Impulsivity in rodents is tightly regulated by a complex bidirectional fronto‐striatal network (Dalley, Mar, Economidou, & Robbins, ; Dalley & Robbins, ). Specifically, response control is regulated by the balance of dopamine levels in the core and the shell region of the nucleus accumbens (Baarendse et al., ; Dalley & Robbins, ; Diergaarde et al., ), which is modulated by afferents from the PFC (Luchicchi et al., ), ventral hippocampus (Abela, Dougherty, Fagen, Hill, & Chudasama, ), anterior cingulate cortex and by the ascending monoamine systems (Dalley & Robbins, ; Dalley et al., ). Notably, nucleus accumbens dopamine is altered both after early life stress (Baarendse et al., ; Bosker et al., ; Oswald et al., ; Watt, Weber, Davies, & Forster, ) and in other APP mouse models of familial AD (Perez et al., ; Von Linstow et al., ), which may explain the more impulsive phenotype we observed in both conditions.…”