Median raphe region stimulation alone generates remote, but not recent fear memory traces

The median raphe region (MRR) is believed to control the fear circuitry indirectly, by influencing the encoding and retrieval of fear memories by amygdala, hippocampus and prefrontal cortex. Here we show that in addition to this established role, MRR stimulation may alone elicit the emergence of remote but not recent fear memories. We substituted electric shocks with optic stimulation of MRR in C57BL/6N male mice in an optogenetic conditioning paradigm and found that stimulations produced agitation, but not fear, during the conditioning trial. Contextual fear, reflected by freezing was not present the next day, but appeared after a 7 days incubation. The optogenetic silencing of MRR during electric shocks ameliorated conditioned fear also seven, but not one day after conditioning. The optogenetic stimulation patterns (50Hz theta burst and 20Hz) used in our tests elicited serotonin release in vitro and lead to activation primarily in the periaqueductal gray examined by c-Fos immunohistochemistry. Earlier studies demonstrated that fear can be induced acutely by stimulation of several subcortical centers, which, however, do not generate persistent fear memories. Here we show that the MRR also elicits fear, but this develops slowly over time, likely by plastic changes induced by the area and its connections. These findings assign a specific role to the MRR in fear learning. Particularly, we suggest that this area is responsible for the durable sensitization of fear circuits towards aversive contexts, and by this, it contributes to the persistence of fear memories. This suggests the existence a bottom-up control of fear circuits by the MRR, which complements the top-down control exerted by the medial prefrontal cortex

Abstracts from the 20th International Symposium on Signal Transduction at the Blood-Brain Barriers

https://deepblue.lib.umich.edu/bitstream/2027.42/138963/1/12987_2017_Article_71.pd

A Hotel Atlantis**** superior Medical, Wellness & Conference szálloda vendégelégedettség mérése, és wellness részlegének innovációja

Dolgozatom témája a hajdúszoboszlói Hotel Atlantis vendégelégedettség mérése, és ez alapján innovációs terv készítése.BSc/BAegészségügyi szervező alapszakmagyarnappaliV

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Pentapeptides derived from A beta 1-42 protect modulatory effect of A beta fibrils - an in vivo electrophysiological study

Short fragments and fragment analogues of beta-amyloid 1-42 peptide (A beta 1-42) display a protective effect against A beta-mediated neurotoxicity. After consideration of our earlier results with in vitro bioassay of synthetic A beta-recognition peptides and toxic fibrillar amyloids, five pentapeptides were selected as putative neuroprotective agents: Phe-Arg-His-Asp-Ser amide (A beta 4-8) and Gly-Arg-His-Asp-Ser amide (an analogue of A beta 4-8), Leu-Pro-Tyr-Phe-Asp amide (an analogue of A beta 17-21), Arg-Ile-Ile-Gly-Leu amide (an analogue of A beta 30-34), and Arg-Val-Val-Ile-Ala amide (an analogue of A beta 38-42). In vitro electrophysiological experiments on rat brain slices demonstrated that four of these peptides counteracted with the field excitatory postsynaptic potential-attenuating effect of A beta 1-42; only Arg-Val-Val-Ile-Ala amide proved inactive. In in vivo experiments using extracellular single-unit recordings combined with iontophoresis, all these pentapeptides except Arg-Val-Val-Ile-Ala amide protected neurons from the NMDA response-enhancing effect of A beta 1-42 in the hippocampal CA1 region. These results suggest that A beta recognition sequences may serve as leads for the design of novel neuroprotective compounds

Endomorphin-2, an endogenous tetrapeptide, protects against A beta 1-42 in vitro and in vivo

The underlying cause of Alzheimer's disease ( AD) is thought to be the beta-amyloid aggregates formed mainly by A beta 1-42 peptide. Protective pentapeptides [ e. g., Leu-Pro-Phe-Phe-Asp (LPFFD)] have been shown to prevent neuronal toxicity of A beta 1-42 by arresting and reversing fibril formation. Here we report that an endogenous tetrapeptide, endomorphin-2 (End-2, amino acid sequence: YPFF), defends against A beta 1-42 induced neuromodulatory effects at the cellular level. Although End-2 does not interfere with the kinetics of A beta fibrillogenesis according to transmission electron microscopic studies and quasielastic light scattering measurements, it binds to A beta 1-42 during aggregation, as revealed by tritium-labeled End-2 binding assay and circular dichroism measurements. The tetrapeptide attenuates the inhibitory effect on cellular redox activity of A beta 1-42 in a dose-dependent manner, as measured by 3-(4,5-dimethylthiazolyl-2)-2,-5-diphenyltetrazolium bromide (MTT) assay. In vitro and in vivo electrophysiological experiments show that End-2 also protects against the field excitatory postsynaptic potential attenuating and the NMDA-evoked responseenhancing effect of A beta 1-42. Studies using [D-Ala ( 2), N-Me-Phe (4), Gly (5)-ol]-enkephalin (DAMGO), a mu-opioid receptor agonist, show that the protective effects of the tetrapeptide are not mu-receptor modulated. The endogenous tetrapeptide End-2 may serve as a lead compound for the drug development in the treatment of AD