The molecular processes that establish fear memory are complex and involve a combination of genetic and epigenetic influences. Dysregulation of these processes can manifest in humans as a range of fear-related anxiety disorders like post-traumatic stress disorders (PTSD). In the present study, immunohistochemistry for acetyl H3, H4, c-fos, CBP (CREB-binding protein) in the infralimbic prefrontal cortex (IL-PFC) and prelimbic prefrontal cortex (PL-PFC) of mPFC (medial prefrontal cortex) and basal amygdala (BA), lateral amygdala (LA), centrolateral amygdala (CeL), centromedial amygdala (CeM) of the amygdala was performed to link region-specific histone acetylation to fear and extinction learning. It was found that the PL-PFC and IL-PFC along with the sub-regions of the amygdala responded differentially to the fear learning and extinction. Following fear learning, c-fos and CBP expression and acetylation of H3 and H4 increased in the BA, LA, CeM, and CeL and the PL-PFC but not in the IL-PFC as compared to the naive control. Similarly, following extinction learning, c-fos and CBP expression increased in BA, LA, CeL, and IL-PFC but not in PL-PFC and CeM as compared to the naive control and conditioned group. However, the acetylation of H3 increased in both IL and PL as opposed to H4 which increased only in the IL-PFC following extinction learning. Overall, region-specific activation in amygdala and PFC following fear and extinction learning as evident by the c-fos activation paralleled the H3/H4 acetylation in these regions. These results suggest that the differential histone acetylation in the PFC and amygdala subnuclei following fear learning and extinction may be associated with the region-specific changes in the neuronal activation pattern resulting in more fear/less fear.

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ObjectiveThe hallmark of anxiety disorders is excessive fear. Previous studies have suggested that selective neural projections from Basal nucleus of stria terminalis (BNST) to amygdala and vice-versa precisely control the fear learning process. However the exact mechanism how the BNST controls fear consolidation and its extinction is largely unknown. In the present study we observed the changes in the BNST sub-regions following fear conditioning and its extinction.MethodsThe change in the number of positive neurons was determined by immunohistochemistry for Acetyl H3 (Histone 3), Acetyl H4 (Histone 4), cAMP response element binding Protein (CBP) and c-fos in three sub-regions of the BNST namely the anterio-lateral BNST (STLP) and anterio-medial BNST (STMA), and lateral-ventral BNST (STLV) of rats subjected to auditory fear conditioning and extinction.ResultsWe found significant increase in the number of CBP, acetyl H3 and acetyl H4 positive neurons in the STMA and STLV but not in the STLP after fear conditioning. However, following fear extinction the number of CBP, acetyl H3 and acetyl H4 positive neurons increased significantly in the STLP but not in the STMA and STLV. Similar changes were observed in the number of c-fos positive neurons after fear consolidation and extinction.ConclusionThe results from this study suggest that the differential histone acetylation in the different sub-regions of the BNST following fear learning and its extinction may be responsible for changes in the neuronal activation patterns resulting in either fear or less fear.

<p>In the present study, a fear-conditioning model in rats was used to gauge the changes in the histone acetylation level in the<br />different nuclei of amygdala during fear memory consolidation and its extinction. It was found by immunohistochemical<br />examination of Amygdala that during the fear memory consolidation histone H3 acetylation level was significantly<br />increased in the Central amygdala (CeA), the output of the fear circuitry, as compared to the unconditioned group and<br />subsequently, when this fear memory was extinguished during fear extinction, the histone H3 acetylation levels decreased<br />significantly as compared to the conditioned group. However, in another nuclei of the amygdala, the intercalated cells<br />(ITCs) the Acetyl H3 levels increased during extinction and but not in the conditioned group as compared to the<br />unconditioned group. The p-ERK and p-CREB levels also significantly varied in the different nuclei of amygdala<br />between the two groups and showed correlation with the Histone acetylation changes observed in these groups. In<br />conclusion the present study points out that the memory formation, during fear memory consolidation and its extinction,<br />may be dependent on differential neuronal activity under epigenetic control through acetylation at k-9 residue of histone<br />H3, in different regions of the amygdala as evident by the p-ERK and p-CREB activation, which are the markers for<br />activity of neurons and memory formation.</p>

Physical and mental well-being is treasure for mankind in a competitive and progressive global scenario. For a country, result oriented tasks can be accomplished only with its healthy population. Along with many diseases of global concern, neurological disorders have drawn concern globally as these are sharing an increasing proportion in global burden of diseases. Further cases of neurodegenerative disorders, majorly affecting aged population, have been recently reported to record a considerable increase which has complicated the health and care-giving (old age homes) services as part of public health. Many public health policies have been laid down by many developed and developing countries in accordance of WHO guidelines which in turn based on GBD studies, made till date. Major share of neurodegenerative disorders is contributed by Alzheimer’s Disease, Parkinson’s Disease, Amyotrophic Lateral Sclerosis & Multiple Sclerosis. The recent past has witnessed growing number of deaths and disability adjusted life years, DALY, caused by neurodegenerative diseases. Public health services and related government policies are not enough, according to WHO, to properly address the current situation. Lack of public awareness towards neurological disorders of all kind, is one of the major challenges to Figure out actual data; for prevalence of neuro-disorders.