Differential Contribution of Anterior and Posterior Midcingulate Subregions to Distal and Proximal Threat Reactivity in Marmosets.

The midcingulate cortex (MCC) is associated with cognition and emotion regulation. Structural and correlational functional evidence suggests that rather than being homogenous, the MCC may have dissociable functions that can be mapped onto distinct subregions. In this study, we use the marmoset monkey to causally investigate the contributions of two proposed subregions of the MCC: the anterior and posterior midcingulate cortices (aMCC and pMCC) to behavioral and cardiovascular correlates of threat processing relevant to anxiety disorders. Transient inactivation of the aMCC decreased anxiety-like responses to a postencounter distal threat, namely an unfamiliar human intruder, while inactivation of the pMCC showed a mild but opposing effect. Furthermore, although inactivation of neither MCC subregions had any effect on basal cardiovascular activity, aMCC inactivation blunted the expression of both cardiovascular and behavioral conditioned responses to a predictable proximal threat (a rubber snake) during the extinction in a Pavlovian conditioning task, with pMCC inactivation having again an opposing effect, but primarily on the behavioral response. These findings suggest that the MCC is indeed functionally heterogeneous with regards to its role in threat processing, with aMCC providing a marked facilitative contribution to the expression of the emotional response to both proximal and distal threat.

A Study into the Evolutionary Divergence of the Core Promoter Elements of PRPF31 and TFPT.

Mutations in PRPF31 have been implicated in retinitis pigmentosa, a blinding disease caused by degeneration of rod photoreceptors. The disease mechanism in the majority of cases is haploinsufficiency. Crucially, attempts at generation of animal models of disease have proved unsuccessful, yielding animals with a visual phenotype that does not mirror human disease. This suggests that, in these animals, the transcriptional regulation of PRPF31 is different to humans and compared to other species. Study of the evolution of the PRPF31 core promoter has important implications for our understanding of human disease, as disease phenotype is modified by differentially expressed alleles in the population. PRPF31 lies in a head-to-head arrangement with TFPT, a gene involved in cellular apoptosis. The two genes were shown to share common regulatory elements in the human genome. In this study, the core promoters of PRPF31 and TFPT were characterised by dual-luciferase reporter assay using genomic DNA from the green monkey, domestic dog and house mouse. It was found that the core promoters were conserved between human and monkey. In dog, the TFPT core promoter was conserved, but different PRPF31 gene architecture meant the gene was controlled by a long-range promoter lying some 2000bp from the transcription start site. There was very low level of conservation (<20%) of the PRPF31 5' region between mouse and human. It was shown that mouse populations did not show variable Prpf31 expression levels, revealing a potential explanation for the lack of phenotype observed in the Prpf31 knock-out mouse model.