RESUMO
Impairments in social behavior are observed in a range of neuropsychiatric disorders and several lines of evidence have demonstrated that dysfunction of the prefrontal cortex (PFC) plays a central role in social deficits. We have previously shown that loss of neuropsychiatric risk gene Cacna1c that codes for the Cav1.2 isoform of L-type calcium channels (LTCCs) in the PFC result in impaired sociability as tested using the three-chamber social approach test. In this study we aimed to further characterize the nature of the social deficit associated with a reduction in PFC Cav1.2 channels (Cav1.2PFCKO mice) by testing male mice in a range of social and nonsocial tests while examining PFC neural activity using in vivo GCaMP6s fiber photometry. We found that during the first investigation of the social and non-social stimulus in the three-chamber test, both Cav1.2PFCKO male mice and Cav1.2PFCGFP controls spent significantly more time with the social stimulus compared to a non-social object. In contrast, during repeat investigations while Cav1.2PFCWT mice continued to spend more time with the social stimulus, Cav1.2PFCKO mice spent equal amount of time with both social and non-social stimuli. Neural activity recordings paralleled social behavior with increase in PFC population activity in Cav1.2PFCWT mice during first and repeat investigations, which was predictive of social preference behavior. In Cav1.2PFCKO mice, there was an increase in PFC activity during first social investigation but not during repeat investigations. These behavioral and neural differences were not observed during a reciprocal social interaction test nor during a forced alternation novelty test. To evaluate a potential deficit in reward-related processes, we tested mice in a three-chamber test wherein the social stimulus was replaced by food. Behavioral testing revealed that both Cav1.2PFCWT and Cav1.2PFCKO mice showed a preference for food over object with significantly greater preference during repeat investigation. Interestingly, there was no increase in PFC activity when Cav1.2PFCWT or Cav1.2PFCKO first investigated the food however activity significantly increased in Cav1.2PFCWT mice during repeat investigations of the food. This was not observed in Cav1.2PFCKO mice. In summary, a reduction in Cav1.2 channels in the PFC suppresses the development of a sustained social preference in mice that is associated with lack of PFC neuronal population activity that may be related to deficits in social reward.
RESUMO
The importance of electron deficient Tp ligands motivates the introduction of electron-withdrawing substituents into the scorpionate framework. Since perfluorophenyltris(pyrazol-1-yl)borate affects significant anodic shifts in half-cell potentials in their metal complexes relative those of phenyltris(pyrazol-1-yl)borate analogues, the tuning opportunities achieved using 3,4,5-trifluorophenyl- and 3,5-bis(trifluoromethyl)phenyl(pyrazol-1-yl)borates were explored. Bis(amino)boranes ((3,4,5-F)C6H2)B(NMe2)2 and ((3,5-CF3)C6H3)B(NMe2)2 are precursors to fluorinated tris(pyrazol-1-yl)phenylborates. Thallium salts of these scorpionates exhibit bridging asymmetric κ3-N,N,N coordination modes consistent with the reduced π-basicity of the fluorinated phenyl substituents relative those of other structurally characterized tris(pyrazol-1-yl)phenylborates. While a comparative analysis of the spectral and X-ray crystallographic data for classical Mo(0), Mo(II), Mn(I), Fe(II) and Cu(II) complexes of [((3,4,5-F)C6H2)Bpz3]- and [((3,5-CF3)C6H3)Bpz3]- could not differentiate these ligands with respect to their metal-based electronic impacts, cyclic voltammetry suggests that 3,4,5-trifluorophenyl- and 3,5-bis(trifluoromethyl)phenyl(pyrazol-1-yl)borates affect similar anodic shifts within their metal complexes, with coordination of [((3,5-CF3)C6H3)Bpz3]- rendering metal centers more difficult to oxidize, and sometimes even more difficult to oxidize than their [C6F5Bpz3]- analogues. These data suggest that the extent of phenyl substituent fluorination necessary to minimize metal center electron-richness in phenyltris(pyrazol-1-yl)borate complexes cannot be confidently predicted.
