Somatostatin Signaling in Neuronal Cilia Is Criticalfor Object Recognition Memory

Abstract

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.

Differential antiinflammatory and antinociceptive effects of the somatostatin analogs octreotide and pasireotide in a mouse model of immune‐mediated arthritis

“…In addition, rabbit monoclonal anti-SSTR2A antibody (clone UMB-1) was used at a dilution of 1:10. These polyclonal and monoclonal anti-SSTR antibodies have been extensively characterized previously (26)(27)(28)(29)(30)(31).…”

TULP3 bridges the IFT-A complex and membrane phosphoinositides to promote trafficking of G protein-coupled receptors into primary cilia

“…Cilia in mature neurons can also act as extrasynaptic compartments in order to modulate neuronal function. Disruption of IFT in adult mice, possibly acting through the proopiomelanocortin (POMC)-expressing hypothalamic axis, result in hyperphagia-induced obesity (Davenport et al 2007), while Sstr3 signaling in the hippocampus is important in synaptic plasticity and novelty detection (Einstein et al 2010). However, our knowledge of the mechanisms by which IFT might modulate sensory signaling in primary cilia is incomplete.…”

Restoration of Mitochondrial Dysfunction in 6-Hydroxydopamine Induced Parkinson’s disease: a Complete Review

“…is able to activating cAMP/CREB in the hippocampal region responsible for memory improvement [424]. Moreover FSK 50 μM direct potentiates synaptic response and induced LTP [425,426].…”