Most neurons possess a single, nonmotile cilium that projects out from the cell surface. These microtubule-based organelles are important in brain development and neurogenesis; however, their function in mature neurons is unknown. Cilia express a complement of proteins distinct from other neuronal compartments, one of which is the somatostatin receptor subtype SST 3 . We show here that SST 3 is critical for object recognition memory in mice. sst3 knock-out mice are severely impaired in discriminating novel objects, whereas they retain normal memory for object location. Further, systemic injection of an SST 3 antagonist (ACQ090) disrupts recall of familiar objects in wild-type mice. To examine mechanisms of SST 3 , we tested synaptic plasticity in CA1 hippocampus. Electrically evoked long-term potentiation (LTP) was normal in sst3 knock-out mice, while adenylyl cyclase/cAMP-mediated LTP was impaired. The SST 3 antagonist also disrupted cAMP-mediated LTP. Basal cAMP levels in hippocampal lysate were reduced in sst3 knock-out mice compared with wild-type mice, while the forskolin-induced increase in cAMP levels was normal. The SST 3 antagonist inhibited forskolin-stimulated cAMP increases, whereas the SST 3 agonist L-796,778 increased basal cAMP levels in hippocampal slices but not hippocampal lysate. Our results show that somatostatin signaling in neuronal cilia is critical for recognition memory and suggest that the cAMP pathway is a conserved signaling motif in cilia. Neuronal cilia therefore represent a novel nonsynaptic compartment crucial for signaling involved in a specific form of synaptic plasticity and in novelty detection.

Volume-dependent anion channels permeable for Cl− and amino acids are thought to play an important role in the homeostasis of cell volume. Astrocytes are the main cell type in the mammalian brain showing volume perturbations under physiological and pathophysiological conditions. We investigated the involvement of tyrosine phosphorylation in hyposmotic medium-induced [3H]taurine andd-[3H]aspartate release from primary astrocyte cultures. The tyrosine kinase inhibitors tyrphostin 23 and tyrphostin A51 partially suppressed the volume-dependent release of [3H]taurine in a dose-dependent manner with half-maximal effects at ∼40 and 1 μM, respectively. In contrast, the release ofd-[3H]aspartate was not significantly affected by these agents in the same concentration range. The inactive analog tyrphostin 1 had no significant effect on the release of both amino acids. The data obtained suggest the existence of at least two volume-dependent anion channels permeable to amino acids in astrocyte cultures. One of these channels is permeable to taurine and is under the control of tyrosine kinase(s). The other is permeable to both taurine and aspartate, but its volume-dependent regulation does not require tyrosine phosphorylation.

Background Maternal and perinatal death surveillance and response (MPDSR) is a system of identifying, analysing and learning lessons from such deaths in order to respond and prevent future deaths, and has been recommended by WHO and implemented in many low-and-middle income settings in recent years. However, there is limited documentation of experience with MPDSR in humanitarian settings. A meeting on MPDSR in humanitarian settings was convened by WHO, UNICEF, CDC and Save the Children, UNFPA and UNHCR on 17th–18th October 2019, informed by semi-structured interviews with a range of professionals, including expert attendees. Consultation findings Interviewees revealed significant obstacles to full implementation of the MPDSR process in humanitarian settings. Many obstacles were familiar to low resource settings in general but were amplified in the context of a humanitarian crisis, such as overburdened services, disincentives to reporting, accountability gaps, a blame approach, and politicisation of mortality. Factors more unique to humanitarian contexts included concerns about health worker security and moral distress. There are varying levels of institutionalisation and implementation capacity for MPDSR within humanitarian organisations. It is suggested that if poorly implemented, particularly with a punitive or blame approach, MPDSR may be counterproductive. Nevertheless, successes in MPDSR were described whereby the process led to concrete actions to prevent deaths, and where death reviews have led to improved understanding of complex and rectifiable contextual factors leading to deaths in humanitarian settings. Conclusions Despite the challenges, examples exist where the lessons learnt from MPDSR processes have led to improved access and quality of care in humanitarian contexts, including successful advocacy. An adapted approach is required to ensure feasibility, with varying implementation being possible in different phases of crises. There is a need for guidance on MPDSR in humanitarian contexts, and for greater documentation and learning from experiences.

No abstract