Thus, new spine structures grew to comparable extents at LMTs and in CA1 in wild-type and β-Adducin−/− mice upon environmental enrichment, but extra synapses failed Adriamycin solubility dmso to form in the mutant mice. This remarkable finding suggests that extra spines can be maintained in the adult CNS upon enrichment even when these fail to establish synapses. The presence of such synapse-free structures is reminiscent of observations

that while the geometry of neuronal circuits maximizes potential synaptic contacts ( Wen et al., 2009), actual synapses are established selectively among potential synaptic partners ( Petreanu et al., 2009 and Oviedo et al., 2010). Our results echo several recent studies that have temporally dissociated local anatomical growth from synaptogenesis during development and under conditions of enhanced plasticity ( Nägerl et al., 2007, Antonova et al., 2009 and Hofer et al., 2009). Taken together, these findings suggest that in adult plasticity one set of signals may induce spine and filopodial growth, and a second set of subsequent signals may regulate synaptogenesis at those new synaptogenic structures ( Figure 8). The early growth of spines may couple an ABT-199 research buy increase in potential synaptogenesis sites to the initial plasticity-inducing event, whereas subsequent synaptogenesis may be specifically coupled to

memory consolidation processes. The mechanisms that locally control synaptogenesis and synapse maintenance in the adult remain to be determined, but our results using β-Adducin−/− mice

suggest that their elucidation will be important to understand the cellular basis for long-term memory processes upon learning. We found that several processes specifically mafosfamide enhanced upon enrichment were not affected by the absence of β-Adducin in the mutant mice. These included elevated neurogenesis in the hippocampus, elevated spinogenesis at LMTs and in CA1, and improved short-term memory. Our findings are consistent with the notion that increased neurogenesis is not required for some of the behavioral effects of environmental enrichment (Meshi et al., 2006). By contrast, enriched mice failed to establish new synapses in the absence of β-Adducin, and instead of improving long-term hippocampus-dependent memory upon learning, enrichment worsened this memory in β-Adducin−/− mice. Enhanced hippocampus-dependent memory was also suppressed in enriched wild-type mice upon PKC inhibition, i.e., under conditions that promoted β-Adducin phosphorylation and inhibited AZ disassembly. Together, these results suggest that enhanced learning and memory upon enrichment involves the enhanced rearrangement of synaptic connectivity, consisting of both the disassembly of existing synapses and the assembly of new synapses.