title: Chemogenetic manipulation of ventral pallidal neurons impairs acquisition of sign-tracking in rats.
abstract: Cues associated with rewarding events acquire value themselves as a result of the incentive value of the reward being transferred to the cue. Consequently, presentation of a reward-paired cue can trigger reward-seeking behaviours towards the cue itself (i.e. sign-tracking). The ventral pallidum (VP) has been demonstrated to be involved in a number of motivated behaviours, both conditioned and unconditioned. However, its contribution to the acquisition of incentive value is unknown. Using a discriminative autoshaping procedure with levers, the effects of disrupting VP activity in rats on the emergence of sign-tracking was investigated using chemogenetics, i.e. Designer Receptors Exclusively Activated by Designer Drugs (DREADDs). Transient disruption of VP neurons [activation of the inhibitory hM4D(Gi) DREADD through systemic injections of clozapine N-oxide (CNO) prior to each autoshaping session] impaired acquisition of sign-tracking (lever press rate) without having any effect on approach to the site of reward delivery (i.e. goal-tracking) or on the expression of sign-tracking after it was acquired. In addition, electrophysiological recordings were conducted in freely behaving rats following VP DREADD activation. The majority of VP units that were responsive to CNO injections exhibited rapid inhibition relative to baseline, a subset of CNO-responsive units showed delayed excitation, and a smaller subset displayed a mixed response of inhibition and excitation following CNO injections. It is argued that disruption of VP during autoshaping specifically disrupted the transfer of incentive value that was attributed to the lever cue, suggesting a surprisingly fundamental role for the VP in acquiring, compared with expressing, Pavlovian incentive values.
authors.affiliation: Department of Psychological and Brain Sciences, Dartmouth College, 6207 Moore Hall, Hanover, NH, 03755, USA.
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Chang
authors.affiliation: Department of Psychological and Brain Sciences, Dartmouth College, 6207 Moore Hall, Hanover, NH, 03755, USA.
authors.forename: Travis P
authors.initials: TP
authors.lastname: Todd
authors.affiliation: Department of Psychological and Brain Sciences, Dartmouth College, 6207 Moore Hall, Hanover, NH, 03755, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Bucci
authors.affiliation: Department of Psychological and Brain Sciences, Dartmouth College, 6207 Moore Hall, Hanover, NH, 03755, USA.
authors.forename: Kyle S
authors.initials: KS
authors.lastname: Smith
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D066187:Basal Forebrain / Q000187:drug effects / Q000502:physiology*; D003024:Clozapine / Q000031:analogs & derivatives / Q000494:pharmacology; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology*; D003463:Cues; D000229:Dependovirus / Q000235:genetics; D015198:Designer Drugs / Q000494:pharmacology; D004567:Electrodes, Implanted; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006040:Goals; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009483:Neuropsychological Tests; D011619:Psychotropic Drugs / Q000494:pharmacology; D020318:Rats, Long-Evans; D012201:Reward
chemical_list: D001426:Bacterial Proteins; D015198:Designer Drugs; D008164:Luminescent Proteins; D011619:Psychotropic Drugs; C434479:citrine protein, bacteria; D003024:Clozapine; C079149:clozapine N-oxide
keywords: DREADDs; reward; sign-tracking; ventral pallidum