Somatostatin signaling in neuronal cilia is critical for object recognition memory.

Kathleen Schildroth // Publications // Mar 24 2010

PubMed ID: 20335466

Author(s): Einstein EB, Patterson CA, Hon BJ, Regan KA, Reddi J, Melnikoff DE, Mateer MJ, Schulz S, Johnson BN, Tallent MK. Somatostatin signaling in neuronal cilia is critical for object recognition memory. J Neurosci. 2010 Mar 24;30(12):4306-14. doi: 10.1523/JNEUROSCI.5295-09.2010. PMID 20335466

Journal: The Journal Of Neuroscience : The Official Journal Of The Society For Neuroscience, Volume 30, Issue 12, Mar 2010

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.