F Messanvi1, A Perkins2, J du Hoffmann3, Y Chudasama2,3. 1. Section on Behavioral Neuroscience, National Institute of Mental Health, Bethesda, MD, USA. kokoefany.messanvi@nih.gov. 2. Section on Behavioral Neuroscience, National Institute of Mental Health, Bethesda, MD, USA. 3. Rodent Behavioral Core, National Institute of Mental Health, Bethesda, MD, USA.
Abstract
RATIONALE: The neuropeptide galanin has been implicated in a wide range of pathological conditions in which frontal and temporal structures are compromised. It works through three subtypes of G-protein-coupled receptors. One of these, the galanin receptor 1 (Gal-R1) subtype, is densely expressed in the ventral hippocampus (vHC) and ventral prefrontal cortex (vPFC); two brain structures that have similar actions on behavioral control. We hypothesize that Gal-R1 contributes to cognitive-control mechanisms that require hippocampal-prefrontal cortical circuitry. OBJECTIVE: To examine the effect of local vHC and vPFC infusions of M617, a Gal-R1 agonist, on inhibitory mechanisms of response control. METHODS: Different cohorts of rats were implanted with bilateral guide cannulae targeting the vPFC or the vHC. Following infusion of the Gal-R1 agonist, we examined the animals' behavior using a touchscreen version of the 5-choice reaction time task (5-choice task). RESULTS: The Gal-R1 agonist produced opposing behaviors in the vPFC and vHC, leading to disruption of impulse control when infused in the vPFC but high impulse control when infused into the vHC. This contrast between areas was accentuated when we added variability to the timing of the stimulus, which led to long decision times and reduced accuracy in the vPFC group but a general improvement in performance accuracy in the vHC group. CONCLUSIONS: These results provide the first evidence of a selective mechanism of Gal-R1-mediated modulation of impulse control in prefrontal-hippocampal circuitry.
RATIONALE: The neuropeptidegalanin has been implicated in a wide range of pathological conditions in which frontal and temporal structures are compromised. It works through three subtypes of G-protein-coupled receptors. One of these, the galanin receptor 1 (Gal-R1) subtype, is densely expressed in the ventral hippocampus (vHC) and ventral prefrontal cortex (vPFC); two brain structures that have similar actions on behavioral control. We hypothesize that Gal-R1 contributes to cognitive-control mechanisms that require hippocampal-prefrontal cortical circuitry. OBJECTIVE: To examine the effect of local vHC and vPFC infusions of M617, a Gal-R1 agonist, on inhibitory mechanisms of response control. METHODS: Different cohorts of rats were implanted with bilateral guide cannulae targeting the vPFC or the vHC. Following infusion of the Gal-R1 agonist, we examined the animals' behavior using a touchscreen version of the 5-choice reaction time task (5-choice task). RESULTS: The Gal-R1 agonist produced opposing behaviors in the vPFC and vHC, leading to disruption of impulse control when infused in the vPFC but high impulse control when infused into the vHC. This contrast between areas was accentuated when we added variability to the timing of the stimulus, which led to long decision times and reduced accuracy in the vPFC group but a general improvement in performance accuracy in the vHC group. CONCLUSIONS: These results provide the first evidence of a selective mechanism of Gal-R1-mediated modulation of impulse control in prefrontal-hippocampal circuitry.
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