In the contextual fear conditioning, mice learn the association between an aversive stimulus, a mild foot shock, and the context in which it was delivered. In mice that have formed an associative memory, a second exposure to the same context induces a fearful response expressed as freezing or immobility, parameters used to quantify the formation of memory (Maren, 2001). We found that mice stereotaxically injected with rAAV-shVEGFD showed significantly lower levels of freezing during the 24 hr test session than did mice injected with rAAV-shSCR ( Figure 8H). The reduction in freezing levels was not due to decreased locomotor activity or pain sensitivity because the basal

exploratory activity and reaction to shock during the training session were not different between the

two groups ( Figures selleck compound 8I and 8J). These findings together with the results obtained with the Morris water maze indicate that VEGFD is important for memory formation. In this study, we identify VEGFD as a regulator of neuronal dendrite geometry. VEGFD mediates the effects of synaptic activity and nuclear calcium-CaMKIV signaling on the maintenance of complex dendrite arborization, which is necessary for memory formation. this website Neurons, even once fully developed, remain plastic and undergo activity-dependent functional or structural alterations. Changes in gene expression – induced by synaptic activity and calcium transients propagating toward and into the nucleus (Chawla et al., 1998, Hardingham et al., 1997, Hardingham et al., 2001 and Zhang et al., 2009) – are often essential for the long-term maintenance of adaptive responses (Hardingham and Bading, 2010 and Greer and Greenberg, 2008). Dendritic trees, the branched projections of the input-receiving ends of neurons, are prime targets for activity-regulated structural alterations. The geometry of dendrites specifies the connectivity of neurons and strongly influences how signals are integrated and transmitted to the cell soma and therefore also which output

is produced. Changes in the lengths and branching patterns of dendrites would be expected to alter not only the performance of a neuron but also the computational power of the network Thalidomide the neuron is part of, ultimately causing changes in the organism’s behavior. Support for such a link between dendritic architecture and cognitive abilities comes from theoretical considerations and mathematical modeling (Häusser et al., 2000 and Segev and London, 2000) as well as from brain morphology studies of neurological diseases. In particular, shortening and simplification of dendrites have been observed in a variety of disorders that are associated with mental retardation or cognitive deficits, including genetic abnormalities, such as Down syndrome or Rett syndrome (Kaufmann and Moser, 2000), neurodegenerative conditions, including Alzheimer’s disease and aging (Dickstein et al.