Chronic activation of the 5-HT(2) receptor reduces 5-HT neurite density as studied in organotypic slice cultures

The serotonin system densely innervates the brain and is implicated in psychopathological processes. Here we studied the effect of serotonin and serotonin pharmacological compounds on the outgrowth of serotonergic projections using organotypic slice co-cultures of hippocampus and dorsal raphe nuclei. Immunocytochemical analysis showed that several serotonergic neurites had grown into the target slice within 7 days in culture, after which the neurite density stabilized. These projections expressed the serotonin-synthesizing enzyme Tryptophan hydroxylase and the serotonin transporter and contained several serotonin-positive varicosities that also accumulated presynaptic markers. Chronic application of a 5-HT(2) agonist reduced the serotonergic neurite density, without effects on survival of serotonergic neurons. In contrast, application of a 5-HT(1A) agonist or the serotonin transporter inhibitor fluoxetine did not affect serotonergic neurite density. We conclude that serotonergic connectivity was reproduced in vitro and that the serotonin neurite density is inhibited by chronic activation of the 5-HT(2) receptor

Cross-talk between signaling pathways leading to defense against pathogens and insects

In nature, plants interact with a wide range of organisms, some of which are harmful (e.g. pathogens, herbivorous insects), while others are beneficial (e.g. growth-promoting rhizobacteria, mycorrhizal fungi, and predatory enemies of herbivores). During the evolutionary arms race between plants and their attackers, primary and secondary immune responses evolved to recognize common or highly specialized features of microbial pathogens (Chisholm et al., 2006), resulting in sophisticated mechanisms of defense

An analysis of the morphology and submarine landslide potential of the upper and middle continental slope offshore Fraser Island, Queensland, Australia

This study presents an investigation into the geomorphological, sedimentological and geotechnical properties of submarine landslides present on the continental slope offshore Fraser Island. An extensive range of previously undiscovered features including marginal plateaus, linear rills, ridges and gullies, canyon systems, as well as slides and slumps were identified. Gravity cores (5.65 m and 3.64 m long) taken in the ‘Upper Slope Slide’ (25 km2 in area, 200-300 m thick), and the ‘Middle Slope Slide’ (11 km2 in area, 100-150 m thick) indicate the slide scars contain drapes of Pleistocene to Recent hemipelagic mud. Shorter gravity cores (1.33 m and 0.43 m long) taken adjacent to both slides terminated in stiff muds of upper Pliocene to lower Pleistocene age (Upper Slope Slide), and upper Miocene to lower Pliocene age (Middle Slope Slide). This unique pattern shows that the sediment is being accumulated and protected inside the slide hollows, while being actively removed from the exposed adjacent slopes, most likely by abrasion. Biostratigraphic ages determined for the basal material demonstrate that the seafloor surfaces at both sites are effectively erosional unconformities. The basal, stiff sediments on the upper slope was deposited between 2 and 2.5 Ma BP; this material was scoured and then buried beneath a 1 m thick sediment drape at 0.45 Ma BP. Sediments exposed on the seafloor adjacent to the Middle Slope Slide were dated at around 6-8.5 Ma BP. This indicates that the smooth upper continental slope developed its morphology by the late-mid Pleistocene, while the middle slope is a Post-Pliocene feature. It is thought that Pliocene-Pleistocene geological events including fluctuations in the intensity of surface and abyssal ocean currents are responsible for re-sculpting the continental slope’s morphology and have a) increased abrasion and erosion of the middle and upper slope; while b) suppressed sediment delivery

CaMKII controls neuromodulation via neuropeptide gene expression and axonal targeting of neuropeptide vesicles

Ca2+/calmodulin-dependent kinase II (CaMKII) regulates synaptic plasticity in multiple ways, supposedly including the secretion of neuromodulators like brain-derived neurotrophic factor (BDNF). Here, we show that neuromodulator secretion is indeed reduced in mouse α- and βCaMKII-deficient (αβCaMKII double-knockout [DKO]) hippocampal neurons. However, this was not due to reduced secretion efficiency or neuromodulator vesicle transport but to 40% reduced neuromodulator levels at synapses and 50% reduced delivery of new neuromodulator vesicles to axons. αβCaMKII depletion drastically reduced neuromodulator expression. Blocking BDNF secretion or BDNF scavenging in wild-type neurons produced a similar reduction. Reduced neuromodulator expression in αβCaMKII DKO neurons was restored by active βCaMKII but not inactive βCaMKII or αCaMKII, and by CaMKII downstream effectors that promote cAMP-response element binding protein (CREB) phosphorylation. These data indicate that CaMKII regulates neuromodulation in a feedback loop coupling neuromodulator secretion to βCaMKII- and CREB-dependent neuromodulator expression an

Psychophysiological responses underlying unresolved loss and trauma in the Adult Attachment Interview

Unresolved loss/trauma in the context of the Adult Attachment Interview (AAI) has been theorised to result from dissociative processing of fear-related memories and ideas. To examine the plausibility of this model, this study tested hypothesised associations between unresolved loss/trauma and indicators of autonomic nervous system (ANS) reactivity. First-time pregnant women (N = 235) participated in the AAI while heart rate (interbeat interval; IBI) and indicators of parasympathetic reactivity (respiratory sinus arrhythmia; RSA) and sympathetic reactivity (pre-ejection period; PEP, skin conductance level; SCL) were recorded. Using multilevel modelling, ANS reactivity was examined in relation to topic (loss/trauma versus other questions); discussion of actual loss/trauma; classification of unresolved/disorganised; and unresolved responses during the interview. Responses to loss/trauma questions and discussion of loss were associated with respectively larger and smaller IBIs. There was no moderation by unresolved/disorganised status. Unresolved responses about loss were associated with smaller IBIs. Participants classified as unresolved/disorganised showed decreasing PEP and blunted SCL throughout the whole interview. The findings suggest that unresolved speech about loss co-occurs with physiological arousal, although the inconclusive findings regarding parasympathetic and sympathetic nervous system responses fail to clearly support the role of fear

How young adults view older people: exploring the pathways of constructing a group image after participation in an intergenerational programme

In recent years, a multitude of intergenerational contact programmes and interventions has emerged to counteract ageism among young adults. Research on these programmes and its supposed effect on ageism often start from the assumption that intergenerational contact follows a largely linear process in which a high level of encounters, in the right setting, decreases ageism and negative stereotyping. The purpose of this article is to critically examine this assumption by focussing on the underlying process of intergenerational contact, rather than examining the positive or negative outcome. Using in-depth interviews with 35 young adults, we found that although conditions and mediating factors during the contact do play a role in the outcome of intergroup contact, the process of contact is rather varied and does not follow a linear path. The results reveal that whether or not a positive contact experience translates into a changed group image of older people is related to the positioning of such experience within the young adults? personal frame of reference. We found that this has to do with the young adults having diverse and both positive and negative previous experiences, their grandparent-grandchild relationship, stories from others and personal characteristics. With this study, we point to the complexity of intergenerational contact and highlight potential pathways leading to varying group images of ?the old?.Prevention, Population and Disease management (PrePoD)Public Health and primary car

The promises of inclusive research methodologies: relational design and praxis

This article explores the potential and challenges of inclusive research methodologies when working with older individuals with lower literacy levels. We present inclusive approaches developed during our research and discuss their implications for methodology and individual well-being among older adults with lower literacy levels. Our key insight is that the promise of inclusive research lies in relational design and praxis. Prioritizing meaningful relationships between researchers and participants, we emphasize the importance of considering participants as active contributors rather than mere informants. Creating a safe and supportive environment fosters trust, empowerment, and meaningful contributions from participants. Flexibility and adaptability in research approaches, including phased informed consent and the minimizing of written language, enhance participants' self-confidence and trust in their own voices. This approach empowers participants in co-creating knowledge, which strengthens the trustworthiness and validity of research results. Inclusive research, while promising, requires researchers to navigate ethical dilemmas, invest time in building rapport, and adapt to participants' needs. It challenges traditional research norms, emphasizing ethical engagement, meaningful participation, and tangible outcomes that benefit both researchers and participants. Employing inclusive research strategies, despite their departure from traditional praxis, ensures that the voices of older individuals with lower literacy levels are respected. This shift enhances the validity of knowledge, promotes co-creation, and fosters feelings of inclusiveness and empowerment. These promises underscore the importance of embracing inclusive research methodologies in contemporary research practices.Prevention, Population and Disease management (PrePoD)Public Health and primary car

Somatodendritic secretion in oxytocin neurons is upregulated during the female reproductive cycle

During the female reproductive cycle, hypothalamic oxytocin (OT) neurons undergo sharp changes in excitability. In lactating mammals, bursts of electrical activity of OT neurons result in the release of large amounts of OT in the bloodstream, which causes milk ejection. One hypothesis is that OT neurons regulate their own firing activity and that of nearby OT neurons by somatodendritic release of OT. In this study, we show that OT neuron activity strongly reduces inhibitory synaptic transmission to these neurons. This effect is blocked by antagonists of both adenosine and OT receptors and is mimicked by OT application. Inhibition of soluble N-ethylmaleimide-sensitive factor attachment protein receptor complex formation by tetanus toxin completely blocked the stimulation-induced reduction in inhibitory input, as did the calcium chelator BAPTA. During lactation, the readily releasable pool of secretory vesicles in OT cell bodies was doubled, and calcium currents were upregulated. This resulted in an increased inhibition of GABAergic synaptic transmission by somatodendritic release during lactation compared with the adult virgin stage. These results demonstrate that somatodendritic release is augmented during lactation, which is a novel form of plasticity to change the strength of synaptic transmission