Review Prefrontal executive and cognitive functions in rodents: neural and neurochemical substrates Jeffrey W. Dalley * , Rudolf N. Cardinal, Trevor W. Robbins Department of Experimental Psychology, University of Cambridge, Downing Street, Cambridge CB2 3EB, UK Abstract The prefrontal cortex has been implicated in a variety of cognitive and executive processes, including working memory, decision-making, inhibitory response control, attentional set-shifting and the temporal integration of voluntary behaviour. This article reviews current progress in our understanding of the rodent prefrontal cortex, especially evidence for functional divergence of the anatomically distinct sub-regions of the rat prefrontal cortex. Recent findings suggest clear distinctions between the dorsal (precentral and anterior cingulate) and ventral (prelimbic, infralimbic and medial orbital) sub-divisions of the medial prefrontal cortex, and between the orbitofrontal cortex (ventral orbital, ventrolateral orbital, dorsal and ventral agranular cortices) and the adjacent medial wall of the prefrontal cortex. The dorso-medial prefrontal cortex is implicated in memory for motor responses, including response selection, and the temporal processing of information. Ventral regions of the medial prefrontal cortex are implicated in interrelated ‘supervisory’ attentional functions, including attention to stimulus features and task contingencies (or action–outcome rules), attentional set-shifting, and behavioural flexibility. The orbitofrontal cortex is implicated in lower- order discriminations, including reversal of stimulus–reward associations (reversal learning), and choice involving delayed reinforcement. It is anticipated that a greater understanding of the prefrontal cortex will come from using tasks that load specific cognitive and executive processes, in parallel with discovering new ways of manipulating the different sub-regions and neuromodulatory systems of the prefrontal cortex. q 2004 Elsevier Ltd. All rights reserved. Keywords: Prefrontal cortex; Orbitofrontal cortex; Inhibitory control; Cognition; Visuo-spatial attention; Spatial working memory; Noradrenaline; Dopamine; Acetylcholine; Serotonin Contents 1. Introduction ........................................................................... 770 2. The rodent prefrontal cortex: structural organization ............................................. 770 3. Functions of the rodent prefrontal cortex ...................................................... 771 4. Mnemonic processes .................................................................... 771 5. Temporal sequencing of behaviour .......................................................... 772 6. Attentional processes .................................................................... 772 6.1. The 5-choice serial reaction time task .................................................... 773 6.1.1. Lesion studies ............................................................... 774 6.1.2. Neuromodulatory influences ..................................................... 774 6.1.3. Functional neurochemistry ...................................................... 775 0149-7634/$ - see front matter q 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.neubiorev.2004.09.006 Neuroscience and Biobehavioral Reviews 28 (2004) 771–784 www.elsevier.com/locate/neubiorev * Corresponding author. Tel.: C44 1223 765 291; fax: C44 1223 333 564. E-mail address: jwd20@cam.ac.uk (J.W. Dalley).