Journal Article

Prefrontal cortex output circuits guide reward seeking through divergent cue encoding

Voets, Elisa S., Mohorn, Emily P., Robinson, J. Elliott, Stuber, Garret D., Namboodiri, Vijay M. K., Kosyk, Oksana, Rossi, Mark A., Matan, Ana M., McHenry, Jenna A., Resendez, Shanna L., Otis, James M.

2017

Overview

The prefrontal cortex is a critical neuroanatomical hub for controlling motivated behaviours across mammalian species 1 , 2 , 3 . In addition to intra-cortical connectivity, prefrontal projection neurons innervate subcortical structures that contribute to reward-seeking behaviours, such as the ventral striatum and midline thalamus 4 . While connectivity among these structures contributes to appetitive behaviours 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , how projection-specific prefrontal neurons encode reward-relevant information to guide reward seeking is unknown. Here we use in vivo two-photon calcium imaging to monitor the activity of dorsomedial prefrontal neurons in mice during an appetitive Pavlovian conditioning task. At the population level, these neurons display diverse activity patterns during the presentation of reward-predictive cues. However, recordings from prefrontal neurons with resolved projection targets reveal that individual corticostriatal neurons show response tuning to reward-predictive cues, such that excitatory cue responses are amplified across learning. By contrast, corticothalamic neurons gradually develop new, primarily inhibitory responses to reward-predictive cues across learning. Furthermore, bidirectional optogenetic manipulation of these neurons reveals that stimulation of corticostriatal neurons promotes conditioned reward-seeking behaviour after learning, while activity in corticothalamic neurons suppresses both the acquisition and expression of conditioned reward seeking. These data show how prefrontal circuitry can dynamically control reward-seeking behaviour through the opposing activities of projection-specific cell populations. Neurons that project from the prefrontal cortex to either the nucleus accumbens or paraventricular thalamus receive different inputs, differentially encode reward-predictive cues, and have opposing effects on reward seeking during cue presentation. Control of reward-seeking behaviour Projections from the prefrontal cortex to the nucleus accumbens and paraventricular thalamus contribute to reward-seeking behaviours, but the type of reward-relevant information that these prefrontal-cortex neurons encode is unknown. Garret Stuber and colleagues show that these two populations of projection neuron receive different inputs, differentially encode reward-predictive cues, and have opposing effects on reward seeking when cues are presented. These findings show how the prefrontal cortex can dynamically control reward-seeking behaviour through the opposing activities of anatomically segregated, projection-specific cell populations.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/378/1662 / 631/378/3920 / 692/699/476/5 / Animal behavior / Animals / Appetitive Behavior - physiology / Brain / Calcium - analysis / Conditioning, Classical - physiology / Cues / Humanities and Social Sciences / letter / Male / Mice / Mice, Inbred C57BL / Microscopy, Fluorescence, Multiphoton / Molecular Imaging / multidisciplinary / Neural circuitry / Neural Pathways / Neurological research / Neurology / Neuronal Plasticity / Neurons / Neurons - physiology / Neuropsychology / Nucleus Accumbens - cytology / Nucleus Accumbens - physiology / Physiological aspects / Prefrontal cortex / Prefrontal Cortex - cytology / Prefrontal Cortex - physiology / Reward / Rewards (Psychology) / Rodents / Science / Thalamus - cytology / Thalamus - physiology