Galanin receptor 1 expressing neurons in hippocampal-prefrontal circuitry modulate goal directed attention and impulse control
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Background
Neuropeptides like galanin are increasingly recognized as modulators of cognitive pathways. Galanin has been implicated in a wide range of pathological conditions in which frontal and temporal structures are compromised. Recently, we discovered that direct pharmacological stimulation of galanin receptor type 1 (GalR1) in the ventral prefrontal cortex (vPFC) and ventral hippocampus (vHC) led to opposing effects on attention and impulse control behavior. In the present study, we investigate how neurons expressing GalR1 in these two areas differentially contribute to these behaviors.
Methods
We used multiplex fluorescent in situ-hybridization to characterize the distribution of GalR1 mRNA in the vPFC and vHC. We assessed behavior in rats using the 5-Choice task. We developed a novel viral approach to gain genetic access to GalR1-expressing neurons in the vPFC and vHC, and used optogenetic stimulation and fiber photometric analysis to gauge the contribution of GalR1 on different phases of the 5-choice task.
Results
We found that GalR1 is expressed in glutamatergic neurons in both the vPFC and vHC, and that optogenetic excitation of GalR1 expressing neurons in the vPFC, but not vHC, selectively disrupts attention. The calcium dynamics in GalR1-expressing neurons revealed opposing activity in the vPFC and vHC which was consistent with our previous work demonstrating differential behavioral effects induced by GalR1 activating in these regions.
Conclusions
We discovered that GalR1-expressing neurons in the vPFC and vHC have distinct activity profiles linked to unique cognitive signals and behavioral outcomes. This region- and response-specific intrinsic activity shapes the expression of executive-control behaviors.
